Outline of Salivary Gland Pathogenesis of Sjögren’s Syndrome and Current Therapeutic Approaches
Abstract
:1. Introduction
2. Changes in the Salivary Gland Histology in SS
3. Mechanisms Underlying the Formation of Salivary Gland Lesions in pSS
3.1. Background of the Development of Salivary Gland Lesions
3.2. Role of DCs in Salivary Glands and Lymph Nodes
3.3. Role of CD4+ Th, CD8+ T Cells in Salivary Glands
3.4. Role of Tregs
3.5. Role of B Cells and Formation of eGCs
3.6. Role of PD-1 and the SS-like Pathology Induced by Anti-PD-1 Antibodies
4. Criteria for the Diagnosis and Evaluation of Disease Activity
5. Treatment of Xerostomia
5.1. Pilocarpine
5.2. Cevimeline
5.3. Sialendoscopy
6. Treatment with Anti-Rheumatic Drugs
Iguratimod
7. Biological Therapy for Molecular Targets
7.1. Rituximab
7.2. Epratuzumab
7.3. Belimumab
7.4. Belimumab Plus Rituximab
7.5. Ianalumab
7.6. Abatacept
7.7. Iscalimab
7.8. Prezalumab (MED15872/AMG557)
Drugs | Authors Year [Ref] | No. of Subjects | ESSDAI (0–123) | ESSPRI (0–10) | Oral Dryness (VAS) | Unstimulated Salivary Flow | Stimulated Salivary Flow |
---|---|---|---|---|---|---|---|
(mL/min) | (mL/min) | ||||||
Rituximab | Meijer et al. 2010 | 30 | W0 W48 | W0 W48 | |||
(anti-CD20) | [209] | C: 0.06 → 0.05 | C: 0.7 → 0.18 | ||||
T: 0.17 → 0.18 | T: 0.92 → 0.66 | ||||||
Carubbi et al. | 41 | W0 W120 | W0 W120 | W0 W120 | |||
2013 [210] | C: 19.8 → 8.8 | C: 72 → 51.8 | C: 0.08 → 0.1 | ||||
T: 20.3 → 5.2 | T: 72 → 25.1 | T: 0.08 → 0.4 | |||||
Bowman et al. | 133 | W0 W48 | W0 W48 | W0 W48 | W0 W48 | ||
2017 [211] | C: 6.0 → 4.5 | C: 6.7 → 4.5 | C: 77.3 → 70.5 | C: 0.08 → 0.04 | |||
T: 5.3 → 6.3 | T: 6.4 → 6.3 | T: 75.3 → 66.4 | T: 0.08 → 0.07 | ||||
Epratuzumab | Steinfeld et al. | 16 | Physician | Patient | |||
(anti-CD22) | 2006 [216] | assessment VAS | assessment VAS | Improvement rate | |||
W0 W32 | W0 W32 | W18 W32 | |||||
56 → 26 | 62 → 40 | 34% → 46% | |||||
Belimumab | De Vita et al. | 28 | W0 W52 | W0 W52 | W28 W52 | ||
(anti-BAFF) | 2015 [219] | 7 → 3 | 6 → 4.5 | 4.9 → 5.1 | |||
Belimumab + | Mariette et al. | 60 | W0 W68 | W0 W68 | W0 W68 | W0 W68 | |
Rituximab | 2022 [222] | C: 10.4 → 8.6 | C:6.4 → 5.7 | C: 0.12 → 0.11 | C: 0.46 → 0.36 | ||
T: 11.0 → 5.0 | T: 6.0 → 5.2 | T: 0.12 → 0.17 | T: 0.72 → 0.9 | ||||
Ianalumab | Dörner et al. 2019 | 27 | Change from W0 | Change from W0 | |||
(anti-BAFF | [223] | W24 | W24 | ||||
receptor) | C: −2 | C: −0.03 | |||||
T: −4 | T: −0.3 | ||||||
Bowman et al. | 150 | Change from W0 | |||||
2022 [224] | to W24 (300 mg iv) | ||||||
−1.92 | |||||||
Abatacept | Meiners et al. | 15 | W0 W24 | W0 W24 | W W24 | W0 W24 | |
(CTLA4-Ig) | 2014 [228] | 11 → 3 | 7.0 → 5.8 | 0.17 → 0.16 | 0.4 → 0.41 | ||
Baer et al. 2021 | 187 | D1 D169 | D1 D169 | D1 D169 | D1 D169 | D1 D169 | |
[229] | C: 10.1 → 6.4 | C: 6.5 → 5.0 | C:6.9 → 5.7 | C: 0.1 → 0.03 | C: 0.9 → 0.1 | ||
T: 8.7 → 5.5 | T: 6.6 → 5.3 | T:7.3 → 6.9 | T: 0.1 → 0.02 | T: 1.1 → 0.1 | |||
Iscalimab (anti-CD40) | Fisher et al. 2020 [233] | 44 | Cohort 2 (10 mg/kg) | ||||
W0 W32 | W0 W32 | ||||||
C:11 → 7 | C:7 → 6.6 | ||||||
T: 11 → 2.1 | T:7 → 4.6 | ||||||
Prezalumab | Mariette et al. | 32 | W0 W49 | ||||
(MED15872/ | 2019 [236] | C:11.6 → 2.3 | |||||
AMG557) | T: 11.8 → 3.8 | ||||||
(anti-ICOSL) |
8. Future Prospectives (Figure 5)
8.1. Mesenchymal Stem Cells (MSCs)
8.2. Chimeric Antigen Receptor T (CART) Cells
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Jonsson, R.; Theander, E.; Sjöström, B.; Brokstad, K.; Henriksson, G. Autoantibodies present before symptom onset in primary Sjögren syndrome. JAMA 2013, 310, 1854–1855. [Google Scholar] [CrossRef] [Green Version]
- Risselada, A.P.; Looije, M.F.; Kruize, A.A.; Bijlsma, J.W.; van Roon, J.A. The role of ectopic germinal centers in the immunopathology of primary Sjögren’s syndrome: A systematic review. Semin. Arthritis Rheum. 2013, 42, 368–376. [Google Scholar] [CrossRef] [PubMed]
- Brito-Zerón, P.; Baldini, C.; Bootsma, H.; Bowman, S.J.; Jonsson, R.; Mariette, X.; Sivils, K.; Theander, E.; Tzioufas, A.; Ramos-Casals, M. Sjögren syndrome. Nat. Rev. Dis. Primers 2016, 2, 16047. [Google Scholar] [CrossRef]
- Shiboski, C.H.; Shiboski, S.C.; Seror, R.; Criswell, L.A.; Labetoulle, M.; Lietman, T.M.; Rasmussen, A.; Scofield, H.; Vitali, C.; Bowman, S.J.; et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 2017, 69, 35–45. [Google Scholar] [CrossRef]
- Mariette, X.; Criswell, L.A. Primary Sjögren’s Syndrome. N. Engl. J. Med. 2018, 378, 931–939. [Google Scholar] [CrossRef] [PubMed]
- Nocturne, G.; Virone, A.; Ng, W.F.; Le Guern, V.; Hachulla, E.; Cornec, D.; Daien, C.; Vittecoq, O.; Bienvenu, B.; Marcelli, C.; et al. Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren’s Syndrome. Arthritis Rheumatol. 2016, 68, 977–985. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Du, W.; Han, M.; Zhu, X.; Xiao, F.; Huang, E.; Che, N.; Tang, X.; Zou, H.; Jiang, Q.; Lu, L. The Multiple Roles of B Cells in the Pathogenesis of Sjögren’s Syndrome. Front. Immunol. 2021, 12, 684999. [Google Scholar] [CrossRef]
- Verstappen, G.M.; Pringle, S.; Bootsma, H.; Kroese, F.G.M. Epithelial-immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis. Nat. Rev. Rheumatol. 2021, 17, 333–348. [Google Scholar] [CrossRef] [PubMed]
- Stergiou, I.E.; Goules, A.V.; Voulgarelis, M.; Tzioufas, A.G. Predisposing Factors, Clinical Picture, and Outcome of B-Cell Non-Hodgkin’s Lymphoma in Sjögren’s Syndrome. Immuno 2022, 2, 37. [Google Scholar] [CrossRef]
- Tak, Y.J.; Kim, J.S.; Lee, K.A.; Kim, H.S.; Jin, S.Y. Histological similarity between tubulointerstitial nephritis and salivary gland biopsy in primary Sjögren’s syndrome. Korean J. Intern. Med. 2022, 37, 486–487. [Google Scholar] [CrossRef]
- Björk, A.; Mofors, J.; Wahren-Herlenius, M. Environmental factors in the pathogenesis of primary Sjögren’s syndrome. J. Intern. Med. 2020, 287, 475–492. [Google Scholar] [CrossRef]
- Cafaro, G.; Croia, C.; Argyropoulou, O.D.; Leone, M.C.; Orlandi, M.; Finamore, F.; Cecchettini, A.; Ferro, F.; Baldini, C.; Bartoloni, E. One year in review 2019: Sjögren’s syndrome. Clin. Exp. Rheumatol. 2019, 37 (Suppl. S118), 3–15. [Google Scholar] [PubMed]
- Manfrè, V.; Chatzis, L.G.; Cafaro, G.; Fonzetti, S.; Calvacchi, S.; Fulvio, G.; Navarro Garcia, I.C.; La Rocca, G.; Ferro, F.; Perricone, C.; et al. Sjögren’s syndrome: One year in review 2022. Clin. Exp. Rheumatol. 2022, 40, 2211–2224. [Google Scholar] [CrossRef]
- Leverenz, D.L.; St Clair, E.W. Recent advances in the search for a targeted immunomodulatory therapy for primary Sjögren’s syndrome. F1000Research 2019, 8, 1532. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Parisis, D.; Chivasso, C.; Perret, J.; Soyfoo, M.S.; Delporte, C. Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy. J. Clin. Med. 2020, 9, 2299. [Google Scholar] [CrossRef] [PubMed]
- Pringle, S.; Wang, X.; Bootsma, H.; Spijkervet, F.K.L.; Vissink, A.; Kroese, F.G.M. Small-molecule inhibitors and the salivary gland epithelium in Sjögren’s syndrome. Expert Opin. Investig. Drugs 2019, 28, 605–616. [Google Scholar] [CrossRef]
- Wang, X.; Bootsma, H.; Terpstra, J.; Vissink, A.; van der Vegt, B.; Spijkervet, F.K.L.; Kroese, F.G.M.; Pringle, S. Progenitor cell niche senescence reflects pathology of the parotid salivary gland in primary Sjögren’s syndrome. Rheumatology 2020, 59, 3003–3013. [Google Scholar] [CrossRef] [Green Version]
- Vitali, C.; Bombardieri, S.; Jonsson, R.; Moutsopoulos, H.M.; Alexander, E.L.; Carsons, S.E.; Daniels, T.E.; Fox, P.C.; Fox, R.I.; Kassan, S.S.; et al. Classification criteria for Sjögren’s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group. Ann. Rheum. Dis. 2002, 61, 554–558. [Google Scholar] [CrossRef] [Green Version]
- Chisholm, D.M.; Mason, D.K. Labial salivary gland biopsy in Sjögren’s disease. J. Clin. Pathol. 1968, 21, 656–660. [Google Scholar] [CrossRef]
- Erkılınç, G.; Doğru, A.; Arslan, Y.; Burak Öz, R.; Karahan, N.; Şahin, M.; Çiriş, İ.M. Evaluation of histopathological results of minor salivary gland biopsies in patients with the diagnosis of Sjögren’s syndrome. Arch. Rheumatol. 2022, 37, 49–58. [Google Scholar] [CrossRef]
- Liao, R.; Yang, H.T.; Li, H.; Liu, L.X.; Li, K.; Li, J.J.; Liang, J.; Hong, X.P.; Chen, Y.L.; Liu, D.Z. Recent Advances of Salivary Gland Biopsy in Sjögren’s Syndrome. Front. Med. 2021, 8, 792593. [Google Scholar] [CrossRef] [PubMed]
- Klein, A.; Klein, J.; Chacham, M.; Kleinman, S.; Shuster, A.; Peleg, O.; Ianculovici, C.; Kaplan, I. Acinar Atrophy, Fibrosis and Fatty Changes Are Significantly More Common than Sjogren’s Syndrome in Minor Salivary Gland Biopsies. Medicina 2022, 58, 175. [Google Scholar] [CrossRef]
- Li, N.; Li, L.; Wu, M.; Li, Y.; Yang, J.; Wu, Y.; Xu, H.; Luo, D.; Gao, Y.; Fei, X.; et al. Integrated Bioinformatics and Validation Reveal Potential Biomarkers Associated With Progression of Primary Sjögren’s Syndrome. Front. Immunol. 2021, 12, 697157. [Google Scholar] [CrossRef] [PubMed]
- van Ginkel, M.S.; Haacke, E.A.; Bootsma, H.; Arends, S.; van Nimwegen, J.F.; Verstappen, G.M.; Spijkervet, F.K.L.; Vissink, A.; van der Vegt, B.; Kroese, F.G.M. Presence of intraepithelial B-lymphocytes is associated with the formation of lymphoepithelial lesions in salivary glands of primary Sjögren’s syndrome patients. Clin. Exp. Rheumatol. 2019, 37 (Suppl. S118), 42–48. [Google Scholar] [PubMed]
- Embgenbroich, M.; Burgdorf, S. Current Concepts of Antigen Cross-Presentation. Front. Immunol. 2018, 9, 1643. [Google Scholar] [CrossRef] [Green Version]
- Junker, F.; Gordon, J.; Qureshi, O. Fc Gamma Receptors and Their Role in Antigen Uptake, Presentation, and T Cell Activation. Front. Immunol. 2020, 11, 1393. [Google Scholar] [CrossRef]
- Aho, K.; Koskenvuo, M.; Tuominen, J.; Kaprio, J. Occurrence of rheumatoid arthritis in a nationwide series of twins. J. Rheumatol. 1986, 13, 899–902. [Google Scholar]
- Silman, A.J.; MacGregor, A.J.; Thomson, W.; Holligan, S.; Carthy, D.; Farhan, A.; Ollier, W.E. Twin concordance rates for rheumatoid arthritis: Results from a nationwide study. Br. J. Rheumatol. 1993, 32, 903–907. [Google Scholar] [CrossRef]
- Hutt-Fletcher, L.M. The Long and Complicated Relationship between Epstein-Barr Virus and Epithelial Cells. J. Virol. 2017, 91, e01677-16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gomez, L.M.; Anaya, J.M.; Gonzalez, C.I.; Pineda-Tamayo, R.; Otero, W.; Arango, A.; Martín, J. PTPN22 C1858T polymorphism in Colombian patients with autoimmune diseases. Genes Immun. 2005, 6, 628–631. [Google Scholar] [CrossRef] [Green Version]
- Sun, F.; Li, P.; Chen, H.; Wu, Z.; Xu, J.; Shen, M.; Leng, X.; Shi, Q.; Zhang, W.; Tian, X.; et al. Association studies of TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren’s syndrome in Han Chinese. J. Hum. Genet. 2013, 58, 475–479. [Google Scholar] [CrossRef] [Green Version]
- Burbelo, P.D.; Ambatipudi, K.; Alevizos, I. Genome-wide association studies in Sjögren’s syndrome: What do the genes tell us about disease pathogenesis? Autoimmun. Rev. 2014, 13, 756–761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nezos, A.; Mavragani, C.P. Contribution of Genetic Factors to Sjögren’s Syndrome and Sjögren’s Syndrome Related Lymphomagenesis. J. Immunol. Res. 2015, 2015, 754825. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Song, I.W.; Chen, H.C.; Lin, Y.F.; Yang, J.H.; Chang, C.C.; Chou, C.T.; Lee, M.M.; Chou, Y.C.; Chen, C.H.; Chen, Y.T.; et al. Identification of susceptibility gene associated with female primary Sjögren’s syndrome in Han Chinese by genome-wide association study. Hum. Genet. 2016, 135, 1287–1294. [Google Scholar] [CrossRef]
- Taylor, K.E.; Wong, Q.; Levine, D.M.; McHugh, C.; Laurie, C.; Doheny, K.; Lam, M.Y.; Baer, A.N.; Challacombe, S.; Lanfranchi, H.; et al. Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren’s Syndrome According to Ancestry. Arthritis Rheumatol. 2017, 69, 1294–1305. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rojas, M.; Restrepo-Jiménez, P.; Monsalve, D.M.; Pacheco, Y.; Acosta-Ampudia, Y.; Ramírez-Santana, C.; Leung, P.S.C.; Ansari, A.A.; Gershwin, M.E.; Anaya, J.M. Molecular mimicry and autoimmunity. J. Autoimmun. 2018, 95, 100–123. [Google Scholar] [CrossRef]
- Khatri, B.; Tessneer, K.L.; Rasmussen, A.; Aghakhanian, F.; Reksten, T.R.; Adler, A.; Alevizos, I.; Anaya, J.M.; Aqrawi, L.A.; Baecklund, E.; et al. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells. Nat. Commun. 2022, 13, 4287. [Google Scholar] [CrossRef]
- James, J.A.; Harley, J.B.; Scofield, R.H. Epstein-Barr virus and systemic lupus erythematosus. Curr. Opin. Rheumatol. 2006, 18, 462–467. [Google Scholar] [CrossRef]
- Anaya, J.M.; Restrepo-Jiménez, P.; Ramírez-Santana, C. The autoimmune ecology: An update. Curr. Opin. Rheumatol. 2018, 30, 350–360. [Google Scholar] [CrossRef]
- Otsuka, K.; Sato, M.; Tsunematsu, T.; Ishimaru, N. Virus Infections Play Crucial Roles in the Pathogenesis of Sjögren’s Syndrome. Viruses 2022, 14, 1474. [Google Scholar] [CrossRef]
- Maslinska, M.; Kostyra-Grabczak, K. The role of virus infections in Sjögren’s syndrome. Front. Immunol. 2022, 13, 823659. [Google Scholar] [CrossRef]
- Jog, N.R.; James, J.A. Epstein Barr Virus and Autoimmune Responses in Systemic Lupus Erythematosus. Front. Immunol. 2020, 11, 623944. [Google Scholar] [CrossRef]
- Murata, T.; Sugimoto, A.; Inagaki, T.; Yanagi, Y.; Watanabe, T.; Sato, Y.; Kimura, H. Molecular Basis of Epstein-Barr Virus Latency Establishment and Lytic Reactivation. Viruses 2021, 13, 2344. [Google Scholar] [CrossRef] [PubMed]
- Thorley-Lawson, D.A. EBV Persistence—Introducing the Virus. Curr. Top. Microbiol. Immunol. 2015, 390, 151–209. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Laichalk, L.L.; Thorley-Lawson, D.A. Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J. Virol. 2005, 79, 1296–1307. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morales-Sánchez, A.; Fuentes-Panana, E.M. The Immunomodulatory Capacity of an Epstein-Barr Virus Abortive Lytic Cycle: Potential Contribution to Viral Tumorigenesis. Cancers 2018, 10, 98. [Google Scholar] [CrossRef] [Green Version]
- Kivity, S.; Arango, M.T.; Ehrenfeld, M.; Tehori, O.; Shoenfeld, Y.; Anaya, J.M.; Agmon-Levin, N. Infection and autoimmunity in Sjogren’s syndrome: A clinical study and comprehensive review. J. Autoimmun. 2014, 51, 17–22. [Google Scholar] [CrossRef]
- Agmon-Levin, N.; Dagan, A.; Peri, Y.; Anaya, J.M.; Selmi, C.; Tincani, A.; Bizzaro, N.; Stojanovich, L.; Damoiseaux, J.; Cohen Tervaert, J.W.; et al. The interaction between anti-Ro/SSA and anti-La/SSB autoantibodies and anti-infectious antibodies in a wide spectrum of auto-immune diseases: Another angle of the autoimmune mosaic. Clin. Exp. Rheumatol. 2017, 35, 929–935. [Google Scholar]
- Luckashenak, N.; Schroeder, S.; Endt, K.; Schmidt, D.; Mahnke, K.; Bachmann, M.F.; Marconi, P.; Deeg, C.A.; Brocker, T. Constitutive crosspresentation of tissue antigens by dendritic cells controls CD8+ T cell tolerance in vivo. Immunity 2008, 28, 521–532. [Google Scholar] [CrossRef] [Green Version]
- Kurts, C.; Robinson, B.W.; Knolle, P.A. Cross-priming in health and disease. Nat. Rev. Immunol. 2010, 10, 403–414. [Google Scholar] [CrossRef]
- Bozzacco, L.; Trumpfheller, C.; Huang, Y.; Longhi, M.P.; Shimeliovich, I.; Schauer, J.D.; Park, C.G.; Steinman, R.M. HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC. Eur. J. Immunol. 2010, 40, 36–46. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rizvi, S.M.; Raghavan, M. Mechanisms of function of tapasin, a critical major histocompatibility complex class I assembly factor. Traffic 2010, 11, 332–347. [Google Scholar] [CrossRef] [Green Version]
- Sheng, J.; Chen, Q.; Soncin, I.; Ng, S.L.; Karjalainen, K.; Ruedl, C. A Discrete Subset of Monocyte-Derived Cells among Typical Conventional Type 2 Dendritic Cells Can Efficiently Cross-Present. Cell Rep. 2017, 21, 1203–1214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baker, K.; Qiao, S.W.; Kuo, T.T.; Aveson, V.G.; Platzer, B.; Andersen, J.T.; Sandlie, I.; Chen, Z.; de Haar, C.; Lencer, W.I.; et al. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc. Natl. Acad. Sci. USA 2011, 108, 9927–9932. [Google Scholar] [CrossRef] [PubMed]
- Lerner, M.R.; Andrews, N.C.; Miller, G.; Steitz, J.A. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc. Natl. Acad. Sci. USA 1981, 78, 805–809. [Google Scholar] [CrossRef] [PubMed]
- Gottenberg, J.E.; Cagnard, N.; Lucchesi, C.; Letourneur, F.; Mistou, S.; Lazure, T.; Jacques, S.; Ba, N.; Ittah, M.; Lepajolec, C.; et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren’s syndrome. Proc. Natl. Acad. Sci. USA 2006, 103, 2770–2775. [Google Scholar] [CrossRef] [PubMed]
- Nezos, A.; Gravani, F.; Tassidou, A.; Kapsogeorgou, E.K.; Voulgarelis, M.; Koutsilieris, M.; Crow, M.K.; Mavragani, C.P. Type I and II interferon signatures in Sjogren’s syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren’s related lymphomagenesis. J. Autoimmun. 2015, 63, 47–58. [Google Scholar] [CrossRef] [Green Version]
- Imgenberg-Kreuz, J.; Sandling, J.K.; Almlöf, J.C.; Nordlund, J.; Signér, L.; Norheim, K.B.; Omdal, R.; Rönnblom, L.; Eloranta, M.L.; Syvänen, A.C.; et al. Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren’s syndrome reveals regulatory effects at interferon-induced genes. Ann. Rheum. Dis. 2016, 75, 2029–2036. [Google Scholar] [CrossRef]
- Hall, J.C.; Baer, A.N.; Shah, A.A.; Criswell, L.A.; Shiboski, C.H.; Rosen, A.; Casciola-Rosen, L. Molecular Subsetting of Interferon Pathways in Sjögren’s Syndrome. Arthritis Rheumatol. 2015, 67, 2437–2446. [Google Scholar] [CrossRef] [Green Version]
- Bao, M.; Liu, Y.J. Regulation of TLR7/9 signaling in plasmacytoid dendritic cells. Protein Cell 2013, 4, 40–52. [Google Scholar] [CrossRef] [Green Version]
- Swiecki, M.; Colonna, M. The multifaceted biology of plasmacytoid dendritic cells. Nat. Rev. Immunol. 2015, 15, 471–485. [Google Scholar] [CrossRef] [PubMed]
- Adamson, T.C., 3rd; Fox, R.I.; Frisman, D.M.; Howell, F.V. Immunohistologic analysis of lymphoid infiltrates in primary Sjogren’s syndrome using monoclonal antibodies. J. Immunol. 1983, 130, 203–208. [Google Scholar] [CrossRef]
- Molina, C.; Alliende, C.; Aguilera, S.; Kwon, Y.J.; Leyton, L.; Martínez, B.; Leyton, C.; Pérez, P.; González, M.J. Basal lamina disorganisation of the acini and ducts of labial salivary glands from patients with Sjogren’s syndrome: Association with mononuclear cell infiltration. Ann. Rheum. Dis. 2006, 65, 178–183. [Google Scholar] [CrossRef] [Green Version]
- Voulgarelis, M.; Tzioufas, A.G. Current Aspects of Pathogenesis in Sjögren’s Syndrome. Ther. Adv. Musculoskelet. Dis. 2010, 2, 325–334. [Google Scholar] [CrossRef] [Green Version]
- Christodoulou, M.I.; Kapsogeorgou, E.K.; Moutsopoulos, H.M. Characteristics of the minor salivary gland infiltrates in Sjögren’s syndrome. J. Autoimmun. 2010, 34, 400–407. [Google Scholar] [CrossRef]
- Kaneko, N.; Chen, H.; Perugino, C.A.; Maehara, T.; Munemura, R.; Yokomizo, S.; Sameshima, J.; Diefenbach, T.J.; Premo, K.R.; Chinju, A.; et al. Cytotoxic CD8(+) T cells may be drivers of tissue destruction in Sjögren’s syndrome. Sci. Rep. 2022, 12, 15427. [Google Scholar] [CrossRef] [PubMed]
- Gao, C.Y.; Yao, Y.; Li, L.; Yang, S.H.; Chu, H.; Tsuneyama, K.; Li, X.M.; Gershwin, M.E.; Lian, Z.X. Tissue-Resident Memory CD8+ T Cells Acting as Mediators of Salivary Gland Damage in a Murine Model of Sjögren’s Syndrome. Arthritis Rheumatol. 2019, 71, 121–132. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fujihara, T.; Fujita, H.; Tsubota, K.; Saito, K.; Tsuzaka, K.; Abe, T.; Takeuchi, T. Preferential localization of CD8+ alpha E beta 7+ T cells around acinar epithelial cells with apoptosis in patients with Sjögren’s syndrome. J. Immunol. 1999, 163, 2226–2235. [Google Scholar] [CrossRef]
- Nakamura, H.; Horai, Y.; Shimizu, T.; Kawakami, A. Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome. Int. J. Mol. Sci. 2018, 19, 2369. [Google Scholar] [CrossRef] [Green Version]
- Kong, L.; Ogawa, N.; Nakabayashi, T.; Liu, G.T.; D’Souza, E.; McGuff, H.S.; Guerrero, D.; Talal, N.; Dang, H. Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren’s syndrome. Arthritis Rheum. 1997, 40, 87–97. [Google Scholar] [CrossRef]
- Ogawa, N.; Ping, L.; Zhenjun, L.; Takada, Y.; Sugai, S. Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren’s syndrome. Arthritis Rheum. 2002, 46, 2730–2741. [Google Scholar] [CrossRef] [PubMed]
- Groom, J.R.; Luster, A.D. CXCR3 ligands: Redundant, collaborative and antagonistic functions. Immunol. Cell Biol. 2011, 89, 207–215. [Google Scholar] [CrossRef] [Green Version]
- Romagnani, S.; Parronchi, P.; D’Elios, M.M.; Romagnani, P.; Annunziato, F.; Piccinni, M.P.; Manetti, R.; Sampognaro, S.; Mavilia, C.; De Carli, M.; et al. An update on human Th1 and Th2 cells. Int. Arch. Allergy Immunol. 1997, 113, 153–156. [Google Scholar] [CrossRef] [PubMed]
- Fazilleau, N.; McHeyzer-Williams, L.J.; Rosen, H.; McHeyzer-Williams, M.G. The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat. Immunol. 2009, 10, 375–384. [Google Scholar] [CrossRef] [PubMed]
- Cenerenti, M.; Saillard, M.; Romero, P.; Jandus, C. The Era of Cytotoxic CD4 T Cells. Front. Immunol. 2022, 13, 867189. [Google Scholar] [CrossRef]
- Mosmann, T.R.; Cherwinski, H.; Bond, M.W.; Giedlin, M.A.; Coffman, R.L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 1986, 136, 2348–2357. [Google Scholar] [CrossRef] [PubMed]
- Youinou, P.; Pers, J.O. Disturbance of cytokine networks in Sjögren’s syndrome. Arthritis Res. Ther. 2011, 13, 227. [Google Scholar] [CrossRef] [Green Version]
- Hirano, T.; Ishihara, K.; Hibi, M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 2000, 19, 2548–2556. [Google Scholar] [CrossRef]
- Bromberg, J. Stat proteins and oncogenesis. J. Clin. Investig. 2002, 109, 1139–1142. [Google Scholar] [CrossRef]
- Ghoreschi, K.; Laurence, A.; O’Shea, J.J. Janus kinases in immune cell signaling. Immunol. Rev. 2009, 228, 273–287. [Google Scholar] [CrossRef] [Green Version]
- Verstappen, G.M.; Corneth, O.B.J.; Bootsma, H.; Kroese, F.G.M. Th17 cells in primary Sjögren’s syndrome: Pathogenicity and plasticity. J. Autoimmun. 2018, 87, 16–25. [Google Scholar] [CrossRef]
- van Hamburg, J.P.; Asmawidjaja, P.S.; Davelaar, N.; Mus, A.M.; Colin, E.M.; Hazes, J.M.; Dolhain, R.J.; Lubberts, E. Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum. 2011, 63, 73–83. [Google Scholar] [CrossRef] [PubMed]
- Hsu, H.C.; Yang, P.; Wang, J.; Wu, Q.; Myers, R.; Chen, J.; Yi, J.; Guentert, T.; Tousson, A.; Stanus, A.L.; et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat. Immunol. 2008, 9, 166–175. [Google Scholar] [CrossRef] [PubMed]
- Rangel-Moreno, J.; Carragher, D.M.; de la Luz Garcia-Hernandez, M.; Hwang, J.Y.; Kusser, K.; Hartson, L.; Kolls, J.K.; Khader, S.A.; Randall, T.D. The development of inducible bronchus-associated lymphoid tissue depends on IL-17. Nat. Immunol. 2011, 12, 639–646. [Google Scholar] [CrossRef] [PubMed]
- Wagner, H.; Starzinski-Powitz, A.; Jung, H.; Röllinghoff, M. Induction of I region-restricted hapten-specific cytotoxic T lymphocytes. J. Immunol. 1977, 119, 1365–1368. [Google Scholar] [CrossRef] [PubMed]
- Feighery, C.; Stastny, P. HLA-D region-associated determinants serve as targets for human cell-mediated lysis. J. Exp. Med. 1979, 149, 485–494. [Google Scholar] [CrossRef] [Green Version]
- Patil, V.S.; Madrigal, A.; Schmiedel, B.J.; Clarke, J.; O’Rourke, P.; de Silva, A.D.; Harris, E.; Peters, B.; Seumois, G.; Weiskopf, D.; et al. Precursors of human CD4(+) cytotoxic T lymphocytes identified by single-cell transcriptome analysis. Sci. Immunol. 2018, 3, eaan8664. [Google Scholar] [CrossRef] [Green Version]
- Bano, A.; Pera, A.; Almoukayed, A.; Clarke, T.H.S.; Kirmani, S.; Davies, K.A.; Kern, F. CD28 (null) CD4 T-cell expansions in autoimmune disease suggest a link with cytomegalovirus infection. F1000Research 2019, 8, 327. [Google Scholar] [CrossRef]
- Maehara, T.; Kaneko, N.; Perugino, C.A.; Mattoo, H.; Kers, J.; Allard-Chamard, H.; Mahajan, V.S.; Liu, H.; Murphy, S.J.; Ghebremichael, M.; et al. Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis. J. Clin. Investig. 2020, 130, 2451–2464. [Google Scholar] [CrossRef] [Green Version]
- Hong, X.; Meng, S.; Tang, D.; Wang, T.; Ding, L.; Yu, H.; Li, H.; Liu, D.; Dai, Y.; Yang, M. Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4(+) T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome. Front. Immunol. 2020, 11, 594658. [Google Scholar] [CrossRef]
- Sakaguchi, S.; Sakaguchi, N.; Asano, M.; Itoh, M.; Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995, 155, 1151–1164. [Google Scholar] [CrossRef] [PubMed]
- Asano, M.; Toda, M.; Sakaguchi, N.; Sakaguchi, S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med. 1996, 184, 387–396. [Google Scholar] [CrossRef] [PubMed]
- Fontenot, J.D.; Rasmussen, J.P.; Williams, L.M.; Dooley, J.L.; Farr, A.G.; Rudensky, A.Y. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005, 22, 329–341. [Google Scholar] [CrossRef]
- Francisco, L.M.; Sage, P.T.; Sharpe, A.H. The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 2010, 236, 219–242. [Google Scholar] [CrossRef] [PubMed]
- Pandiyan, P.; Zheng, L.; Ishihara, S.; Reed, J.; Lenardo, M.J. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat. Immunol. 2007, 8, 1353–1362. [Google Scholar] [CrossRef]
- Shevach, E.M. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 2009, 30, 636–645. [Google Scholar] [CrossRef] [Green Version]
- Thornton, A.M.; Shevach, E.M. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998, 188, 287–296. [Google Scholar] [CrossRef] [Green Version]
- Wing, K.; Onishi, Y.; Prieto-Martin, P.; Yamaguchi, T.; Miyara, M.; Fehervari, Z.; Nomura, T.; Sakaguchi, S. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008, 322, 271–275. [Google Scholar] [CrossRef]
- Maynard, C.L.; Harrington, L.E.; Janowski, K.M.; Oliver, J.R.; Zindl, C.L.; Rudensky, A.Y.; Weaver, C.T. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10. Nat. Immunol. 2007, 8, 931–941. [Google Scholar] [CrossRef]
- Collison, L.W.; Workman, C.J.; Kuo, T.T.; Boyd, K.; Wang, Y.; Vignali, K.M.; Cross, R.; Sehy, D.; Blumberg, R.S.; Vignali, D.A. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007, 450, 566–569. [Google Scholar] [CrossRef]
- Kroese, F.G.; Abdulahad, W.H.; Haacke, E.; Bos, N.A.; Vissink, A.; Bootsma, H. B-cell hyperactivity in primary Sjögren’s syndrome. Expert Rev. Clin. Immunol. 2014, 10, 483–499. [Google Scholar] [CrossRef]
- Reed, J.H.; Verstappen, G.M.; Rischmueller, M.; Bryant, V.L. When B cells break bad: Development of pathogenic B cells in Sjögren’s syndrome. Clin. Exp. Rheumatol. 2020, 38 (Suppl. S126), 271–282. [Google Scholar]
- Pontarini, E.; Fabris, M.; Quartuccio, L.; Cappeletti, M.; Calcaterra, F.; Roberto, A.; Curcio, F.; Mavilio, D.; Della Bella, S.; De Vita, S. Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren’s syndrome. Rheumatology 2015, 54, 1429–1434. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Verstappen, G.M.; Kroese, F.G.M.; Bootsma, H. T cells in primary Sjögren’s syndrome: Targets for early intervention. Rheumatology 2021, 60, 3088–3098. [Google Scholar] [CrossRef] [PubMed]
- Carrasco, Y.R.; Batista, F.D. B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity 2007, 27, 160–171. [Google Scholar] [CrossRef] [Green Version]
- Batista, F.D.; Harwood, N.E. The who, how and where of antigen presentation to B cells. Nat. Rev. Immunol. 2009, 9, 15–27. [Google Scholar] [CrossRef]
- Breitfeld, D.; Ohl, L.; Kremmer, E.; Ellwart, J.; Sallusto, F.; Lipp, M.; Förster, R. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J. Exp. Med. 2000, 192, 1545–1552. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rawlings, D.J.; Schwartz, M.A.; Jackson, S.W.; Meyer-Bahlburg, A. Integration of B cell responses through Toll-like receptors and antigen receptors. Nat. Rev. Immunol. 2012, 12, 282–294. [Google Scholar] [CrossRef] [Green Version]
- Daridon, C.; Devauchelle, V.; Hutin, P.; Le Berre, R.; Martins-Carvalho, C.; Bendaoud, B.; Dueymes, M.; Saraux, A.; Youinou, P.; Pers, J.O. Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjögren’s syndrome. Arthritis Rheum. 2007, 56, 1134–1144. [Google Scholar] [CrossRef]
- Lavie, F.; Miceli-Richard, C.; Ittah, M.; Sellam, J.; Gottenberg, J.E.; Mariette, X. B-cell activating factor of the tumour necrosis factor family expression in blood monocytes and T cells from patients with primary Sjögren’s syndrome. Scand. J. Immunol. 2008, 67, 185–192. [Google Scholar] [CrossRef]
- Ramos-Casals, M. The B-lymphocyte stimulator connection in Sjogren’s syndrome. Rheumatology 2013, 52, 223–225. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Del Papa, N.; Vitali, C. Management of primary Sjögren’s syndrome: Recent developments and new classification criteria. Ther. Adv. Musculoskelet. Dis. 2018, 10, 39–54. [Google Scholar] [CrossRef] [Green Version]
- Cancro, M.P.; D’Cruz, D.P.; Khamashta, M.A. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J. Clin. Investig. 2009, 119, 1066–1073. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nayar, S.; Campos, J.; Smith, C.G.; Iannizzotto, V.; Gardner, D.H.; Colafrancesco, S.; Pipi, E.; Kollert, F.; Hunter, K.J.; Brewer, C.; et al. Phosphatidylinositol 3-kinase delta pathway: A novel therapeutic target for Sjögren’s syndrome. Ann. Rheum. Dis. 2019, 78, 249–260. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stebegg, M.; Kumar, S.D.; Silva-Cayetano, A.; Fonseca, V.R.; Linterman, M.A.; Graca, L. Regulation of the Germinal Center Response. Front. Immunol. 2018, 9, 2469. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fisher, B.A.; Jonsson, R.; Daniels, T.; Bombardieri, M.; Brown, R.M.; Morgan, P.; Bombardieri, S.; Ng, W.F.; Tzioufas, A.G.; Vitali, C.; et al. Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren’s syndrome. Ann. Rheum. Dis. 2017, 76, 1161–1168. [Google Scholar] [CrossRef] [PubMed]
- Trivedi, A.; Cornejo, K.M.; O’Donnell, P.; Dresser, K.; Deng, A. Employing immunohistochemical staining to labial minor salivary gland biopsies from patients with Sjogren’s syndrome increases diagnostic certainty. J. Oral Pathol. Med. 2021, 50, 98–102. [Google Scholar] [CrossRef]
- Bryant, V.L.; Ma, C.S.; Avery, D.T.; Li, Y.; Good, K.L.; Corcoran, L.M.; de Waal Malefyt, R.; Tangye, S.G. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: Predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J. Immunol. 2007, 179, 8180–8190. [Google Scholar] [CrossRef]
- Fonseca, V.R.; Romão, V.C.; Agua-Doce, A.; Santos, M.; López-Presa, D.; Ferreira, A.C.; Fonseca, J.E.; Graca, L. The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren’s Syndrome. Arthritis Rheumatol. 2018, 70, 774–784. [Google Scholar] [CrossRef] [Green Version]
- Blokland, S.L.M.; van Vliet-Moret, F.M.; Hillen, M.R.; Pandit, A.; Goldschmeding, R.; Kruize, A.A.; Bouma, G.; van Maurik, A.; Olek, S.; Hoffmueller, U.; et al. Epigenetically quantified immune cells in salivary glands of Sjögren’s syndrome patients: A novel tool that detects robust correlations of T follicular helper cells with immunopathology. Rheumatology 2020, 59, 335–343. [Google Scholar] [CrossRef]
- Lim, H.W.; Hillsamer, P.; Kim, C.H. Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses. J. Clin. Investig. 2004, 114, 1640–1649. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chung, Y.; Tanaka, S.; Chu, F.; Nurieva, R.I.; Martinez, G.J.; Rawal, S.; Wang, Y.H.; Lim, H.; Reynolds, J.M.; Zhou, X.H.; et al. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat. Med. 2011, 17, 983–988. [Google Scholar] [CrossRef] [PubMed]
- Linterman, M.A.; Pierson, W.; Lee, S.K.; Kallies, A.; Kawamoto, S.; Rayner, T.F.; Srivastava, M.; Divekar, D.P.; Beaton, L.; Hogan, J.J.; et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat. Med. 2011, 17, 975–982. [Google Scholar] [CrossRef] [Green Version]
- Zhu, Y.; Zou, L.; Liu, Y.C. T follicular helper cells, T follicular regulatory cells and autoimmunity. Int. Immunol. 2016, 28, 173–179. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allen, C.D.; Okada, T.; Cyster, J.G. Germinal-center organization and cellular dynamics. Immunity 2007, 27, 190–202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Victora, G.D.; Dominguez-Sola, D.; Holmes, A.B.; Deroubaix, S.; Dalla-Favera, R.; Nussenzweig, M.C. Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas. Blood 2012, 120, 2240–2248. [Google Scholar] [CrossRef] [Green Version]
- Mesin, L.; Ersching, J.; Victora, G.D. Germinal Center B Cell Dynamics. Immunity 2016, 45, 471–482. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sundar, K.; Jacques, S.; Gottlieb, P.; Villars, R.; Benito, M.E.; Taylor, D.K.; Spatz, L.A. Expression of the Epstein-Barr virus nuclear antigen-1 (EBNA-1) in the mouse can elicit the production of anti-dsDNA and anti-Sm antibodies. J. Autoimmun. 2004, 23, 127–140. [Google Scholar] [CrossRef]
- Haneji, N.; Nakamura, T.; Takio, K.; Yanagi, K.; Higashiyama, H.; Saito, I.; Noji, S.; Sugino, H.; Hayashi, Y. Identification of alpha-fodrin as a candidate autoantigen in primary Sjögren’s syndrome. Science 1997, 276, 604–607. [Google Scholar] [CrossRef]
- Ramos-Morales, F.; Infante, C.; Fedriani, C.; Bornens, M.; Rios, R.M. NA14 is a novel nuclear autoantigen with a coiled-coil domain. J. Biol. Chem. 1998, 273, 1634–1639. [Google Scholar] [CrossRef] [Green Version]
- Liu, Y.; Liao, X.; Wang, Y.; Chen, S.; Sun, Y.; Lin, Q.; Shi, G. Autoantibody to MDM2: A potential serological marker of primary Sjogren’s syndrome. Oncotarget 2017, 8, 14306–14313. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tong, L.; Koh, V.; Thong, B.Y. Review of autoantigens in Sjögren’s syndrome: An update. J. Inflamm. Res. 2017, 10, 97–105. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kajio, N.; Takeshita, M.; Suzuki, K.; Kaneda, Y.; Yamane, H.; Ikeura, K.; Sato, H.; Kato, S.; Shimizu, H.; Tsunoda, K.; et al. Anti-centromere antibodies target centromere-kinetochore macrocomplex: A comprehensive autoantigen profiling. Ann. Rheum. Dis. 2021, 80, 651–659. [Google Scholar] [CrossRef] [PubMed]
- Waterman, S.A.; Gordon, T.P.; Rischmueller, M. Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren’s syndrome. Arthritis Rheum. 2000, 43, 1647–1654. [Google Scholar] [CrossRef]
- Jordan, R.C.; Masaki, Y.; Takeshita, S.; Speight, P.M.; Sugai, S. High prevalence of B-cell monoclonality in labial gland biopsies of Japanese Sjögren’s syndrome patients. Int. J. Hematol. 1996, 64, 47–52. [Google Scholar] [CrossRef]
- Visser, A.; Verstappen, G.M.; van der Vegt, B.; Vissink, A.; Bende, R.J.; Bootsma, H.; Bos, N.A.; Kroese, F.G.M. Repertoire Analysis of B-Cells Located in Striated Ducts of Salivary Glands of Patients With Sjögren’s Syndrome. Front. Immunol. 2020, 11, 1486. [Google Scholar] [CrossRef]
- Verstappen, G.M.; Ice, J.A.; Bootsma, H.; Pringle, S.; Haacke, E.A.; de Lange, K.; van der Vries, G.B.; Hickey, P.; Vissink, A.; Spijkervet, F.K.L.; et al. Gene expression profiling of epithelium-associated FcRL4(+) B cells in primary Sjögren’s syndrome reveals a pathogenic signature. J. Autoimmun. 2020, 109, 102439. [Google Scholar] [CrossRef]
- Yao, S.; Wang, S.; Zhu, Y.; Luo, L.; Zhu, G.; Flies, S.; Xu, H.; Ruff, W.; Broadwater, M.; Choi, I.H.; et al. PD-1 on dendritic cells impedes innate immunity against bacterial infection. Blood 2009, 113, 5811–5818. [Google Scholar] [CrossRef]
- Xia, L.; Liu, Y.; Wang, Y. PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions. Oncologist 2019, 24, S31–S41. [Google Scholar] [CrossRef] [Green Version]
- Freeman, G.J.; Long, A.J.; Iwai, Y.; Bourque, K.; Chernova, T.; Nishimura, H.; Fitz, L.J.; Malenkovich, N.; Okazaki, T.; Byrne, M.C.; et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 2000, 192, 1027–1034. [Google Scholar] [CrossRef] [Green Version]
- Yokosuka, T.; Takamatsu, M.; Kobayashi-Imanishi, W.; Hashimoto-Tane, A.; Azuma, M.; Saito, T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J. Exp. Med. 2012, 209, 1201–1217. [Google Scholar] [CrossRef] [Green Version]
- Parry, R.V.; Chemnitz, J.M.; Frauwirth, K.A.; Lanfranco, A.R.; Braunstein, I.; Kobayashi, S.V.; Linsley, P.S.; Thompson, C.B.; Riley, J.L. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell Biol. 2005, 25, 9543–9553. [Google Scholar] [CrossRef] [Green Version]
- Riley, J.L. PD-1 signaling in primary T cells. Immunol. Rev. 2009, 229, 114–125. [Google Scholar] [CrossRef] [Green Version]
- Okazaki, T.; Honjo, T. PD-1 and PD-1 ligands: From discovery to clinical application. Int. Immunol. 2007, 19, 813–824. [Google Scholar] [CrossRef] [Green Version]
- Lee, J.; Ahn, E.; Kissick, H.T.; Ahmed, R. Reinvigorating Exhausted T Cells by Blockade of the PD-1 Pathway. For. Immunopathol. Dis. Therap. 2015, 6, 7–17. [Google Scholar] [CrossRef] [Green Version]
- Gordon, S.R.; Maute, R.L.; Dulken, B.W.; Hutter, G.; George, B.M.; McCracken, M.N.; Gupta, R.; Tsai, J.M.; Sinha, R.; Corey, D.; et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 2017, 545, 495–499. [Google Scholar] [CrossRef] [Green Version]
- Barry, K.C.; Hsu, J.; Broz, M.L.; Cueto, F.J.; Binnewies, M.; Combes, A.J.; Nelson, A.E.; Loo, K.; Kumar, R.; Rosenblum, M.D.; et al. A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat. Med. 2018, 24, 1178–1191. [Google Scholar] [CrossRef]
- Nishimura, H.; Nose, M.; Hiai, H.; Minato, N.; Honjo, T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999, 11, 141–151. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Yoshida, T.; Nakaki, F.; Hiai, H.; Okazaki, T.; Honjo, T. Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes. Proc. Natl. Acad. Sci. USA 2005, 102, 11823–11828. [Google Scholar] [CrossRef]
- Cappelli, L.C.; Shah, A.A.; Bingham, C.O., 3rd. Immune-Related Adverse Effects of Cancer Immunotherapy- Implications for Rheumatology. Rheum. Dis. Clin. N. Am. 2017, 43, 65–78. [Google Scholar] [CrossRef] [Green Version]
- Tocut, M.; Brenner, R.; Zandman-Goddard, G. Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibitors. Autoimmun. Rev. 2018, 17, 610–616. [Google Scholar] [CrossRef] [PubMed]
- Warner, B.M.; Baer, A.N.; Lipson, E.J.; Allen, C.; Hinrichs, C.; Rajan, A.; Pelayo, E.; Beach, M.; Gulley, J.L.; Madan, R.A.; et al. Sicca Syndrome Associated with Immune Checkpoint Inhibitor Therapy. Oncologist 2019, 24, 1259–1269. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yura, Y.; Hamada, M. Oral Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors: Salivary Gland Dysfunction and Mucosal Diseases. Cancers 2022, 14, 792. [Google Scholar] [CrossRef] [PubMed]
- Ramos-Casals, M.; Maria, A.; Suárez-Almazor, M.E.; Lambotte, O.; Fisher, B.A.; Hernández-Molina, G.; Guilpain, P.; Pundole, X.; Flores-Chávez, A.; Baldini, C.; et al. Sicca/Sjögren’s syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International ImmunoCancer Registry (ICIR). Clin. Exp. Rheumatol. 2019, 37 (Suppl. S118), 114–122. [Google Scholar]
- Vitali, C.; Bombardieri, S.; Moutsopoulos, H.M.; Balestrieri, G.; Bencivelli, W.; Bernstein, R.M.; Bjerrum, K.B.; Braga, S.; Coll, J.; de Vita, S.; et al. Preliminary criteria for the classification of Sjögren’s syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993, 36, 340–347. [Google Scholar] [CrossRef]
- Pringle, S.; van der Vegt, B.; Wang, X.; van Bakelen, N.; Hiltermann, T.J.N.; Spijkervet, F.K.L.; Vissink, A.; Kroese, F.G.M.; Bootsma, H. Lack of Conventional Acinar Cells in Parotid Salivary Gland of Patient Taking an Anti-PD-L1 Immune Checkpoint Inhibitor. Front. Oncol. 2020, 10, 420. [Google Scholar] [CrossRef] [Green Version]
- Le Goff, M.; Cornec, D.; Jousse-Joulin, S.; Guellec, D.; Costa, S.; Marhadour, T.; Le Berre, R.; Genestet, S.; Cochener, B.; Boisrame-Gastrin, S.; et al. Comparison of 2002 AECG and 2016 ACR/EULAR classification criteria and added value of salivary gland ultrasonography in a patient cohort with suspected primary Sjögren’s syndrome. Arthritis Res. Ther. 2017, 19, 269. [Google Scholar] [CrossRef] [Green Version]
- Billings, M.; Amin Hadavand, M.; Alevizos, I. Comparative analysis of the 2016 ACR-EULAR and the 2002 AECG classification criteria for Sjögren’s syndrome: Findings from the NIH cohort. Oral Dis. 2018, 24, 184–190. [Google Scholar] [CrossRef]
- Seror, R.; Ravaud, P.; Bowman, S.J.; Baron, G.; Tzioufas, A.; Theander, E.; Gottenberg, J.E.; Bootsma, H.; Mariette, X.; Vitali, C. EULAR Sjogren’s syndrome disease activity index: Development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann. Rheum. Dis. 2010, 69, 1103–1109. [Google Scholar] [CrossRef]
- Seror, R.; Bowman, S.J.; Brito-Zeron, P.; Theander, E.; Bootsma, H.; Tzioufas, A.; Gottenberg, J.E.; Ramos-Casals, M.; Dörner, T.; Ravaud, P.; et al. EULAR Sjögren’s syndrome disease activity index (ESSDAI): A user guide. RMD Open 2015, 1, e000022. [Google Scholar] [CrossRef] [Green Version]
- Seror, R.; Ravaud, P.; Mariette, X.; Bootsma, H.; Theander, E.; Hansen, A.; Ramos-Casals, M.; Dörner, T.; Bombardieri, S.; Hachulla, E.; et al. EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI): Development of a consensus patient index for primary Sjogren’s syndrome. Ann. Rheum. Dis. 2011, 70, 968–972. [Google Scholar] [CrossRef] [PubMed]
- Seror, R.; Bootsma, H.; Saraux, A.; Bowman, S.J.; Theander, E.; Brun, J.G.; Baron, G.; Le Guern, V.; Devauchelle-Pensec, V.; Ramos-Casals, M.; et al. Defining disease activity states and clinically meaningful improvement in primary Sjögren’s syndrome with EULAR primary Sjögren’s syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann. Rheum. Dis. 2016, 75, 382–389. [Google Scholar] [CrossRef] [PubMed]
- Luciano, N.; Ferro, F.; Bombardieri, S.; Baldini, C. Advances in salivary gland ultrasonography in primary Sjögren’s syndrome. Clin. Exp. Rheumatol. 2018, 36 (Suppl. S114), 159–164. [Google Scholar]
- Ferguson, M.M. Pilocarpine and other cholinergic drugs in the management of salivary gland dysfunction. Oral Surg. Oral Med. Oral Pathol. 1993, 75, 186–191. [Google Scholar] [CrossRef]
- Nusair, S.; Rubinow, A. The use of oral pilocarpine in xerostomia and Sjögren’s syndrome. Semin. Arthritis Rheum. 1999, 28, 360–367. [Google Scholar] [CrossRef] [PubMed]
- Vivino, F.B.; Al-Hashimi, I.; Khan, Z.; LeVeque, F.G.; Salisbury, P.L., 3rd; Tran-Johnson, T.K.; Muscoplat, C.C.; Trivedi, M.; Goldlust, B.; Gallagher, S.C. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: A randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch. Intern. Med. 1999, 159, 174–181. [Google Scholar] [CrossRef] [PubMed]
- Minagi, H.O.; Ikai, K.; Araie, T.; Sakai, M.; Sakai, T. Benefits of long-term pilocarpine due to increased muscarinic acetylcholine receptor 3 in salivary glands. Biochem. Biophys. Res. Commun. 2018, 503, 1098–1102. [Google Scholar] [CrossRef]
- Fox, R.I.; Konttinen, Y.; Fisher, A. Use of muscarinic agonists in the treatment of Sjögren’s syndrome. Clin. Immunol. 2001, 101, 249–263. [Google Scholar] [CrossRef]
- Papas, A.S.; Sherrer, Y.S.; Charney, M.; Golden, H.E.; Medsger, T.A., Jr.; Walsh, B.T.; Trivedi, M.; Goldlust, B.; Gallagher, S.C. Successful Treatment of Dry Mouth and Dry Eye Symptoms in Sjögren’s Syndrome Patients With Oral Pilocarpine: A Randomized, Placebo-Controlled, Dose-Adjustment Study. J. Clin. Rheumatol. 2004, 10, 169–177. [Google Scholar] [CrossRef]
- Noaiseh, G.; Baker, J.F.; Vivino, F.B. Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren’s syndrome. Clin. Exp. Rheumatol. 2014, 32, 575–577. [Google Scholar]
- Watanabe, M.; Yamada, C.; Komagata, Y.; Kikuchi, H.; Hosono, H.; Itagaki, F. New low-dose liquid pilocarpine formulation for treating dry mouth in Sjögren’s syndrome: Clinical efficacy, symptom relief, and improvement in quality of life. J. Pharm. Health Care Sci. 2018, 4, 4. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, A.; Nakano, H.; Yoneto, K.; Yoneto, C.; Furubayashi, T.; Suzuki, K.; Okae, A.; Ueno, T.; Sakane, T. Topical Xerostomia Treatment with Hyaluronate Sheets Containing Pilocarpine. Biol. Pharm. Bull. 2022, 45, 403–408. [Google Scholar] [CrossRef]
- Fife, R.S.; Chase, W.F.; Dore, R.K.; Wiesenhutter, C.W.; Lockhart, P.B.; Tindall, E.; Suen, J.Y. Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: A randomized trial. Arch. Intern. Med. 2002, 162, 1293–1300. [Google Scholar] [CrossRef] [PubMed]
- Weber, J.; Keating, G.M. Cevimeline. Drugs 2008, 68, 1691–1698. [Google Scholar] [CrossRef] [PubMed]
- Voskoboynik, B.; Babu, K.; Hack, J.B. Cevimeline (Evoxac®) overdose. J. Med. Toxicol. 2011, 7, 57–59. [Google Scholar] [CrossRef] [Green Version]
- Loy, F.; Isola, M.; Masala, C.; Isola, R. Reactivity of human labial glands in response to cevimeline treatment. Anat. Rec. 2021, 304, 2879–2890. [Google Scholar] [CrossRef]
- Guo, Y.F.; Sun, N.N.; Wu, C.B.; Xue, L.; Zhou, Q. Sialendoscopy-assisted treatment for chronic obstructive parotitis related to Sjogren syndrome. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2017, 123, 305–309. [Google Scholar] [CrossRef]
- Capaccio, P.; Canzi, P.; Torretta, S.; Rossi, V.; Benazzo, M.; Bossi, A.; Vitali, C.; Cavagna, L.; Pignataro, L. Combined interventional sialendoscopy and intraductal steroid therapy for recurrent sialadenitis in Sjögren’s syndrome: Results of a pilot monocentric trial. Clin. Otolaryngol. 2018, 43, 96–102. [Google Scholar] [CrossRef]
- Jager, D.J.; Karagozoglu, K.H.; Maarse, F.; Brand, H.S.; Forouzanfar, T. Sialendoscopy of Salivary Glands Affected by Sjögren Syndrome: A Randomized Controlled Pilot Study. J. Oral Maxillofac. Surg. 2016, 74, 1167–1174. [Google Scholar] [CrossRef] [PubMed]
- Karagozoglu, K.H.; Vissink, A.; Forouzanfar, T.; de Visscher, J.; Maarse, F.; Brand, H.S.; van de Ven, P.M.; Jager, D.H.J. Sialendoscopy increases saliva secretion and reduces xerostomia up to 60 weeks in Sjögren’s syndrome patients: A randomized controlled study. Rheumatology 2021, 60, 1353–1363. [Google Scholar] [CrossRef]
- Karagozoglu, K.H.; De Visscher, J.G.; Forouzanfar, T.; van der Meij, E.H.; Jager, D.J. Complications of Sialendoscopy in Patients With Sjögren Syndrome. J. Oral Maxillofac. Surg. 2017, 75, 978–983. [Google Scholar] [CrossRef]
- Du, H.; Fu, Z.; Zhong, Y.; Yuan, Y.; Zhao, J.; Ding, X.; Li, S.; Gao, S.; Zhu, Y.; Song, H.; et al. A randomized controlled trial to verify the irrigation of salivary glands in relieving xerostomia in patients with Sjögren’s syndrome. Front. Immunol. 2022, 13, 1039599. [Google Scholar] [CrossRef]
- Saraux, A.; Pers, J.O.; Devauchelle-Pensec, V. Treatment of primary Sjögren syndrome. Nat. Rev. Rheumatol. 2016, 12, 456–471. [Google Scholar] [CrossRef]
- Fox, P.C.; Datiles, M.; Atkinson, J.C.; Macynski, A.A.; Scott, J.; Fletcher, D.; Valdez, I.H.; Kurrasch, R.H.; Delapenha, R.; Jackson, W. Prednisone and piroxicam for treatment of primary Sjögren’s syndrome. Clin. Exp. Rheumatol. 1993, 11, 149–156. [Google Scholar] [PubMed]
- Priori, R.; Mastromanno, L.; Izzo, R. What about glucocorticoids in primary Sjögren’s syndrome? Clin. Exp. Rheumatol. 2020, 38 (Suppl. S126), 237–244. [Google Scholar]
- Ramos-Casals, M.; Brito-Zerón, P.; Bombardieri, S.; Bootsma, H.; De Vita, S.; Dörner, T.; Fisher, B.A.; Gottenberg, J.E.; Hernandez-Molina, G.; Kocher, A.; et al. EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies. Ann. Rheum. Dis. 2020, 79, 3–18. [Google Scholar] [CrossRef] [Green Version]
- van der Heijden, E.H.M.; Kruize, A.A.; Radstake, T.; van Roon, J.A.G. Optimizing conventional DMARD therapy for Sjögren’s syndrome. Autoimmun. Rev. 2018, 17, 480–492. [Google Scholar] [CrossRef] [PubMed]
- Drosos, A.A.; Skopouli, F.N.; Galanopoulou, V.K.; Kitridou, R.C.; Moutsopoulos, H.M. Cyclosporin a therapy in patients with primary Sjögren’s syndrome: Results at one year. Scand. J. Rheumatol. Suppl. 1986, 61, 246–249. [Google Scholar] [PubMed]
- Imai, F.; Suzuki, T.; Ishibashi, T.; Tanaka, M.; Akiyama, Y.; Dohi, Y. Effect of sulfasalazine on B cell hyperactivity in patients with rheumatoid arthritis. J. Rheumatol. 1994, 21, 612–615. [Google Scholar]
- Skopouli, F.N.; Jagiello, P.; Tsifetaki, N.; Moutsopoulos, H.M. Methotrexate in primary Sjögren’s syndrome. Clin. Exp. Rheumatol. 1996, 14, 555–558. [Google Scholar]
- Gottenberg, J.E.; Ravaud, P.; Puéchal, X.; Le Guern, V.; Sibilia, J.; Goeb, V.; Larroche, C.; Dubost, J.J.; Rist, S.; Saraux, A.; et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: The JOQUER randomized clinical trial. JAMA 2014, 312, 249–258. [Google Scholar] [CrossRef] [PubMed]
- Vivino, F.B.; Bunya, V.Y.; Massaro-Giordano, G.; Johr, C.R.; Giattino, S.L.; Schorpion, A.; Shafer, B.; Peck, A.; Sivils, K.; Rasmussen, A.; et al. Sjogren’s syndrome: An update on disease pathogenesis, clinical manifestations and treatment. Clin. Immunol. 2019, 203, 81–121. [Google Scholar] [CrossRef] [PubMed]
- Jiang, H.; Gao, H.; Wang, Q.; Wang, M.; Wu, B. Molecular mechanisms and clinical application of Iguratimod: A review. Biomed. Pharmacother. 2020, 122, 109704. [Google Scholar] [CrossRef] [PubMed]
- Xu, Y.; Zhu, Q.; Song, J.; Liu, H.; Miao, Y.; Yang, F.; Wang, F.; Cheng, W.; Xi, Y.; Niu, X.; et al. Regulatory Effect of Iguratimod on the Balance of Th Subsets and Inhibition of Inflammatory Cytokines in Patients with Rheumatoid Arthritis. Mediat. Inflamm. 2015, 2015, 356040. [Google Scholar] [CrossRef] [Green Version]
- Zeng, L.; He, Q.; Yang, K.; Hao, W.; Yu, G.; Chen, H. A Systematic Review and Meta-Analysis of 19 Randomized Controlled Trials of Iguratimod Combined With Other Therapies for Sjogren’s Syndrome. Front. Immunol. 2022, 13, 924730. [Google Scholar] [CrossRef]
- Roescher, N.; Tak, P.P.; Illei, G.G. Cytokines in Sjögren’s syndrome. Oral Dis. 2009, 15, 519–526. [Google Scholar] [CrossRef] [Green Version]
- Banerjee, S.; Biehl, A.; Gadina, M.; Hasni, S.; Schwartz, D.M. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs 2017, 77, 521–546. [Google Scholar] [CrossRef]
- Corneth, O.B.J.; Verstappen, G.M.P.; Paulissen, S.M.J.; de Bruijn, M.J.W.; Rip, J.; Lukkes, M.; van Hamburg, J.P.; Lubberts, E.; Bootsma, H.; Kroese, F.G.M.; et al. Enhanced Bruton’s Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease. Arthritis Rheumatol. 2017, 69, 1313–1324. [Google Scholar] [CrossRef] [Green Version]
- Imgenberg-Kreuz, J.; Sandling, J.K.; Björk, A.; Nordlund, J.; Kvarnström, M.; Eloranta, M.L.; Rönnblom, L.; Wahren-Herlenius, M.; Syvänen, A.C.; Nordmark, G. Transcription profiling of peripheral B cells in antibody-positive primary Sjögren’s syndrome reveals upregulated expression of CX3CR1 and a type I and type II interferon signature. Scand. J. Immunol. 2018, 87, e12662. [Google Scholar] [CrossRef] [Green Version]
- Price, E.; Bombardieri, M.; Kivitz, A.; Matzkies, F.; Gurtovaya, O.; Pechonkina, A.; Jiang, W.; Downie, B.; Mathur, A.; Mozaffarian, A.; et al. Safety and efficacy of filgotinib, lanraplenib and tirabrutinib in Sjögren’s syndrome: A randomized, phase 2, double-blind, placebo-controlled study. Rheumatology 2022, 61, 4797–4808. [Google Scholar] [CrossRef]
- Bai, W.; Liu, H.; Dou, L.; Yang, Y.; Leng, X.; Li, M.; Zhang, W.; Zhao, Y.; Zeng, X. Pilot study of baricitinib for active Sjogren’s syndrome. Ann. Rheum. Dis. 2022, 81, 1050–1052. [Google Scholar] [CrossRef] [PubMed]
- Juarez, M.; Diaz, N.; Johnston, G.I.; Nayar, S.; Payne, A.; Helmer, E.; Cain, D.; Williams, P.; Devauchelle-Pensec, V.; Fisher, B.A.; et al. A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren’s syndrome. Rheumatology 2021, 60, 1364–1375. [Google Scholar] [CrossRef] [PubMed]
- Mariette, X.; Ravaud, P.; Steinfeld, S.; Baron, G.; Goetz, J.; Hachulla, E.; Combe, B.; Puéchal, X.; Pennec, Y.; Sauvezie, B.; et al. Inefficacy of infliximab in primary Sjögren’s syndrome: Results of the randomized, controlled Trial of Remicade in Primary Sjögren’s Syndrome (TRIPSS). Arthritis Rheum. 2004, 50, 1270–1276. [Google Scholar] [CrossRef] [PubMed]
- Gueiros, L.A.; France, K.; Posey, R.; Mays, J.W.; Carey, B.; Sollecito, T.P.; Setterfield, J.; Woo, S.B.; Culton, D.; Payne, A.S.; et al. World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögren’s syndrome: A systematic review. Oral Dis. 2019, 25 (Suppl. S1), 102–110. [Google Scholar] [CrossRef] [Green Version]
- Coiffier, B.; Haioun, C.; Ketterer, N.; Engert, A.; Tilly, H.; Ma, D.; Johnson, P.; Lister, A.; Feuring-Buske, M.; Radford, J.A.; et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: A multicenter phase II study. Blood 1998, 92, 1927–1932. [Google Scholar]
- Piro, L.D.; White, C.A.; Grillo-López, A.J.; Janakiraman, N.; Saven, A.; Beck, T.M.; Varns, C.; Shuey, S.; Czuczman, M.; Lynch, J.W.; et al. Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin’s lymphoma. Ann. Oncol. 1999, 10, 655–661. [Google Scholar] [CrossRef]
- Dörner, T.; Burmester, G.R. The role of B cells in rheumatoid arthritis: Mechanisms and therapeutic targets. Curr. Opin. Rheumatol. 2003, 15, 246–252. [Google Scholar] [CrossRef]
- Edwards, J.C.; Szczepanski, L.; Szechinski, J.; Filipowicz-Sosnowska, A.; Emery, P.; Close, D.R.; Stevens, R.M.; Shaw, T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 2004, 350, 2572–2581. [Google Scholar] [CrossRef] [Green Version]
- Meijer, J.M.; Meiners, P.M.; Vissink, A.; Spijkervet, F.K.; Abdulahad, W.; Kamminga, N.; Brouwer, E.; Kallenberg, C.G.; Bootsma, H. Effectiveness of rituximab treatment in primary Sjögren’s syndrome: A randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010, 62, 960–968. [Google Scholar] [CrossRef]
- Carubbi, F.; Cipriani, P.; Marrelli, A.; Benedetto, P.; Ruscitti, P.; Berardicurti, O.; Pantano, I.; Liakouli, V.; Alvaro, S.; Alunno, A.; et al. Efficacy and safety of rituximab treatment in early primary Sjögren’s syndrome: A prospective, multi-center, follow-up study. Arthritis Res. Ther. 2013, 15, R172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bowman, S.J.; Everett, C.C.; O’Dwyer, J.L.; Emery, P.; Pitzalis, C.; Ng, W.F.; Pease, C.T.; Price, E.J.; Sutcliffe, N.; Gendi, N.S.T.; et al. Randomized Controlled Trial of Rituximab and Cost-Effectiveness Analysis in Treating Fatigue and Oral Dryness in Primary Sjögren’s Syndrome. Arthritis Rheumatol. 2017, 69, 1440–1450. [Google Scholar] [CrossRef] [Green Version]
- Fisher, B.A.; Everett, C.C.; Rout, J.; O’Dwyer, J.L.; Emery, P.; Pitzalis, C.; Ng, W.F.; Carr, A.; Pease, C.T.; Price, E.J.; et al. Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: Results of the TRACTISS randomised double-blind multicentre substudy. Ann. Rheum. Dis. 2018, 77, 412–416. [Google Scholar] [CrossRef] [Green Version]
- Souza, F.B.; Porfírio, G.J.; Andriolo, B.N.; Albuquerque, J.V.; Trevisani, V.F. Rituximab Effectiveness and Safety for Treating Primary Sjögren’s Syndrome (pSS): Systematic Review and Meta-Analysis. PLoS ONE 2016, 11, e0150749. [Google Scholar] [CrossRef]
- Engel, P.; Nojima, Y.; Rothstein, D.; Zhou, L.J.; Wilson, G.L.; Kehrl, J.H.; Tedder, T.F. The same epitope on CD22 of B lymphocytes mediates the adhesion of erythrocytes, T and B lymphocytes, neutrophils, and monocytes. J. Immunol. 1993, 150, 4719–4732. [Google Scholar] [CrossRef] [PubMed]
- Tedder, T.F.; Poe, J.C.; Haas, K.M. CD22: A multifunctional receptor that regulates B lymphocyte survival and signal transduction. Adv. Immunol. 2005, 88, 1–50. [Google Scholar] [CrossRef] [PubMed]
- Steinfeld, S.D.; Tant, L.; Burmester, G.R.; Teoh, N.K.; Wegener, W.A.; Goldenberg, D.M.; Pradier, O. Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren’s syndrome: An open-label phase I/II study. Arthritis Res. Ther. 2006, 8, R129. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Navarra, S.V.; Guzmán, R.M.; Gallacher, A.E.; Hall, S.; Levy, R.A.; Jimenez, R.E.; Li, E.K.; Thomas, M.; Kim, H.Y.; León, M.G.; et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: A randomised, placebo-controlled, phase 3 trial. Lancet 2011, 377, 721–731. [Google Scholar] [CrossRef] [PubMed]
- Furie, R.; Rovin, B.H.; Houssiau, F.; Malvar, A.; Teng, Y.K.O.; Contreras, G.; Amoura, Z.; Yu, X.; Mok, C.C.; Santiago, M.B.; et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N. Engl. J. Med. 2020, 383, 1117–1128. [Google Scholar] [CrossRef]
- De Vita, S.; Quartuccio, L.; Seror, R.; Salvin, S.; Ravaud, P.; Fabris, M.; Nocturne, G.; Gandolfo, S.; Isola, M.; Mariette, X. Efficacy and safety of belimumab given for 12 months in primary Sjögren’s syndrome: The BELISS open-label phase II study. Rheumatology 2015, 54, 2249–2256. [Google Scholar] [CrossRef] [Green Version]
- Cambridge, G.; Stohl, W.; Leandro, M.J.; Migone, T.S.; Hilbert, D.M.; Edwards, J.C. Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: Relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum. 2006, 54, 723–732. [Google Scholar] [CrossRef]
- Pers, J.O.; Devauchelle, V.; Daridon, C.; Bendaoud, B.; Le Berre, R.; Bordron, A.; Hutin, P.; Renaudineau, Y.; Dueymes, M.; Loisel, S.; et al. BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren’s syndrome. Arthritis Rheum. 2007, 56, 1464–1477. [Google Scholar] [CrossRef] [PubMed]
- Mariette, X.; Barone, F.; Baldini, C.; Bootsma, H.; Clark, K.L.; De Vita, S.; Gardner, D.H.; Henderson, R.B.; Herdman, M.; Lerang, K.; et al. A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren’s syndrome. JCI Insight 2022, 7, e163030. [Google Scholar] [CrossRef] [PubMed]
- Dörner, T.; Posch, M.G.; Li, Y.; Petricoul, O.; Cabanski, M.; Milojevic, J.M.; Kamphausen, E.; Valentin, M.A.; Simonett, C.; Mooney, L.; et al. Treatment of primary Sjögren’s syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Ann. Rheum. Dis. 2019, 78, 641–647. [Google Scholar] [CrossRef] [PubMed]
- Bowman, S.J.; Fox, R.; Dörner, T.; Mariette, X.; Papas, A.; Grader-Beck, T.; Fisher, B.A.; Barcelos, F.; De Vita, S.; Schulze-Koops, H.; et al. Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren’s syndrome: A randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet 2022, 399, 161–171. [Google Scholar] [CrossRef] [PubMed]
- Ndejembi, M.P.; Teijaro, J.R.; Patke, D.S.; Bingaman, A.W.; Chandok, M.R.; Azimzadeh, A.; Nadler, S.G.; Farber, D.L. Control of memory CD4 T cell recall by the CD28/B7 costimulatory pathway. J. Immunol. 2006, 177, 7698–7706. [Google Scholar] [CrossRef] [Green Version]
- Linsley, P.S.; Nadler, S.G. The clinical utility of inhibiting CD28-mediated costimulation. Immunol. Rev. 2009, 229, 307–321. [Google Scholar] [CrossRef] [PubMed]
- Furst, D.E.; Keystone, E.C.; So, A.K.; Braun, J.; Breedveld, F.C.; Burmester, G.R.; De Benedetti, F.; Dörner, T.; Emery, P.; Fleischmann, R.; et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012. Ann. Rheum. Dis. 2013, 72 (Suppl. S2), ii2–ii34. [Google Scholar] [CrossRef]
- Meiners, P.M.; Vissink, A.; Kroese, F.G.; Spijkervet, F.K.; Smitt-Kamminga, N.S.; Abdulahad, W.H.; Bulthuis-Kuiper, J.; Brouwer, E.; Arends, S.; Bootsma, H. Abatacept treatment reduces disease activity in early primary Sjögren’s syndrome (open-label proof of concept ASAP study). Ann. Rheum. Dis. 2014, 73, 1393–1396. [Google Scholar] [CrossRef]
- Baer, A.N.; Gottenberg, J.E.; St Clair, E.W.; Sumida, T.; Takeuchi, T.; Seror, R.; Foulks, G.; Nys, M.; Mukherjee, S.; Wong, R.; et al. Efficacy and safety of abatacept in active primary Sjögren’s syndrome: Results of a phase III, randomised, placebo-controlled trial. Ann. Rheum. Dis. 2021, 80, 339–348. [Google Scholar] [CrossRef]
- Klaus, S.J.; Pinchuk, L.M.; Ochs, H.D.; Law, C.L.; Fanslow, W.C.; Armitage, R.J.; Clark, E.A. Costimulation through CD28 enhances T cell-dependent B cell activation via CD40-CD40L interaction. J. Immunol. 1994, 152, 5643–5652. [Google Scholar] [CrossRef]
- Elgueta, R.; Benson, M.J.; de Vries, V.C.; Wasiuk, A.; Guo, Y.; Noelle, R.J. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol. Rev. 2009, 229, 152–172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Voynova, E.; Mahmoud, T.; Woods, L.T.; Weisman, G.A.; Ettinger, R.; Braley-Mullen, H. Requirement for CD40/CD40L Interactions for Development of Autoimmunity Differs Depending on Specific Checkpoint and Costimulatory Pathways. Immunohorizons 2018, 2, 54–66. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fisher, B.A.; Szanto, A.; Ng, W.-F.; Bombardieri, M.; Posch, M.G.; Papas, A.S.; Farag, A.M.; Daikeler, T.; Bannert, B.; Kyburz, D. Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren’s syndrome: A multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study. Lancet Rheumatol. 2020, 2, e142–e152. [Google Scholar] [CrossRef]
- Crotty, S. T follicular helper cell differentiation, function, and roles in disease. Immunity 2014, 41, 529–542. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pontarini, E.; Verstappen, G.M.; Grigoriadou, S.; Kroese, F.G.M.; Bootsma, H.; Bombardieri, M. Blocking T cell co-stimulation in primary Sjögren’s syndrome: Rationale, clinical efficacy and modulation of peripheral and salivary gland biomarkers. Clin. Exp. Rheumatol. 2020, 38 (Suppl. S126), 222–227. [Google Scholar]
- Mariette, X.; Bombardieri, M.; Alevizos, I.; Moate, R.; Sullivan, B.; Noaiseh, G.; Kvarnstrom, M.; Rees, W.; Wang, L.; Illei, G. A Phase 2a Study of MEDI5872 (AMG557), a Fully Human Anti-ICOS Ligand Monoclonal Antibody in Patients with Primary Sjogren’s Syndrome. In Sjögren’s Syndrome—Basic & Clinical Science Poster I, Abstract Number 2417, Proceedings of the 2019 ACR/ARP Annual Meeting, Atlanta, GA, USA, 8–13 November 2019; WILEY: Hoboken, NJ, USA, 2019. [Google Scholar]
- Sekiguchi, M.; Iwasaki, T.; Kitano, M.; Kuno, H.; Hashimoto, N.; Kawahito, Y.; Azuma, M.; Hla, T.; Sano, H. Role of sphingosine 1-phosphate in the pathogenesis of Sjögren’s syndrome. J. Immunol. 2008, 180, 1921–1928. [Google Scholar] [CrossRef] [Green Version]
- Yura, Y.; Masui, A.; Hamada, M. Inhibitors of Ceramide- and Sphingosine-Metabolizing Enzymes as Sensitizers in Radiotherapy and Chemotherapy for Head and Neck Squamous Cell Carcinoma. Cancers 2020, 12, 2062. [Google Scholar] [CrossRef]
- Yang, X.X.; Yang, C.; Wang, L.; Zhou, Y.B.; Yuan, X.; Xiang, N.; Wang, Y.P.; Li, X.M. Molecular Mechanism of Sphingosine-1-Phosphate Receptor 1 Regulating CD4(+) Tissue Memory in situ T Cells in Primary Sjogren’s Syndrome. Int. J. Gen. Med. 2021, 14, 6177–6188. [Google Scholar] [CrossRef]
- Brinkmann, V.; Davis, M.D.; Heise, C.E.; Albert, R.; Cottens, S.; Hof, R.; Bruns, C.; Prieschl, E.; Baumruker, T.; Hiestand, P.; et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem. 2002, 277, 21453–21457. [Google Scholar] [CrossRef] [Green Version]
- Brinkmann, V.; Billich, A.; Baumruker, T.; Heining, P.; Schmouder, R.; Francis, G.; Aradhye, S.; Burtin, P. Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis. Nat. Rev. Drug Discov. 2010, 9, 883–897. [Google Scholar] [CrossRef]
- Kappos, L.; Radue, E.W.; O’Connor, P.; Polman, C.; Hohlfeld, R.; Calabresi, P.; Selmaj, K.; Agoropoulou, C.; Leyk, M.; Zhang-Auberson, L.; et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med. 2010, 362, 387–401. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gerossier, E.; Nayar, S.; Froidevaux, S.; Smith, C.G.; Runser, C.; Iannizzotto, V.; Vezzali, E.; Pierlot, G.; Mentzel, U.; Murphy, M.J.; et al. Cenerimod, a selective S1P(1) receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome. Arthritis Res. Ther. 2021, 23, 289. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez-Rey, E.; Gonzalez, M.A.; Varela, N.; O’Valle, F.; Hernandez-Cortes, P.; Rico, L.; Büscher, D.; Delgado, M. Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann. Rheum. Dis. 2010, 69, 241–248. [Google Scholar] [CrossRef]
- Tomar, G.B.; Srivastava, R.K.; Gupta, N.; Barhanpurkar, A.P.; Pote, S.T.; Jhaveri, H.M.; Mishra, G.C.; Wani, M.R. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem. Biophys. Res. Commun. 2010, 393, 377–383. [Google Scholar] [CrossRef]
- Hass, R.; Kasper, C.; Böhm, S.; Jacobs, R. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun. Signal. 2011, 9, 12. [Google Scholar] [CrossRef] [Green Version]
- Munir, H.; McGettrick, H.M. Mesenchymal Stem Cell Therapy for Autoimmune Disease: Risks and Rewards. Stem Cells Dev. 2015, 24, 2091–2100. [Google Scholar] [CrossRef] [PubMed]
- Di Nicola, M.; Carlo-Stella, C.; Magni, M.; Milanesi, M.; Longoni, P.D.; Matteucci, P.; Grisanti, S.; Gianni, A.M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002, 99, 3838–3843. [Google Scholar] [CrossRef]
- Bifari, F.; Lisi, V.; Mimiola, E.; Pasini, A.; Krampera, M. Immune Modulation by Mesenchymal Stem Cells. Transfus. Med. Hemother. 2008, 35, 194–204. [Google Scholar] [CrossRef] [Green Version]
- Jacobs, S.A.; Roobrouck, V.D.; Verfaillie, C.M.; Van Gool, S.W. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells. Immunol. Cell Biol. 2013, 91, 32–39. [Google Scholar] [CrossRef]
- Alunno, A.; Montanucci, P.; Bistoni, O.; Basta, G.; Caterbi, S.; Pescara, T.; Pennoni, I.; Bini, V.; Bartoloni, E.; Gerli, R.; et al. In vitro immunomodulatory effects of microencapsulated umbilical cord Wharton jelly-derived mesenchymal stem cells in primary Sjögren’s syndrome. Rheumatology 2015, 54, 163–168. [Google Scholar] [CrossRef] [Green Version]
- Chen, W.; Yu, Y.; Ma, J.; Olsen, N.; Lin, J. Mesenchymal Stem Cells in Primary Sjögren’s Syndrome: Prospective and Challenges. Stem Cells Int. 2018, 2018, 4357865. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, J.; Wang, D.; Liu, D.; Fan, Z.; Zhang, H.; Liu, O.; Ding, G.; Gao, R.; Zhang, C.; Ding, Y.; et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome. Blood 2012, 120, 3142–3151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jayaraman, J.; Mellody, M.P.; Hou, A.J.; Desai, R.P.; Fung, A.W.; Pham, A.H.T.; Chen, Y.Y.; Zhao, W. CAR-T design: Elements and their synergistic function. EBioMedicine 2020, 58, 102931. [Google Scholar] [CrossRef]
- Maher, J.; Brentjens, R.J.; Gunset, G.; Rivière, I.; Sadelain, M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat. Biotechnol. 2002, 20, 70–75. [Google Scholar] [CrossRef] [PubMed]
- Curran, K.J.; Pegram, H.J.; Brentjens, R.J. Chimeric antigen receptors for T cell immunotherapy: Current understanding and future directions. J. Gene Med. 2012, 14, 405–415. [Google Scholar] [CrossRef] [Green Version]
- Abbott, R.C.; Cross, R.S.; Jenkins, M.R. Finding the Keys to the CAR: Identifying Novel Target Antigens for T Cell Redirection Immunotherapies. Int. J. Mol. Sci. 2020, 21, 515. [Google Scholar] [CrossRef] [Green Version]
- Bhoj, V.G.; Arhontoulis, D.; Wertheim, G.; Capobianchi, J.; Callahan, C.A.; Ellebrecht, C.T.; Obstfeld, A.E.; Lacey, S.F.; Melenhorst, J.J.; Nazimuddin, F.; et al. Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood 2016, 128, 360–370. [Google Scholar] [CrossRef]
- Oh, S.; Payne, A.S. Engineering Cell Therapies for Autoimmune Diseases: From Preclinical to Clinical Proof of Concept. Immune Netw. 2022, 22, e37. [Google Scholar] [CrossRef]
- Majzner, R.G.; Mackall, C.L. Tumor Antigen Escape from CAR T-cell Therapy. Cancer Discov. 2018, 8, 1219–1226. [Google Scholar] [CrossRef] [Green Version]
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Yura, Y.; Hamada, M. Outline of Salivary Gland Pathogenesis of Sjögren’s Syndrome and Current Therapeutic Approaches. Int. J. Mol. Sci. 2023, 24, 11179. https://doi.org/10.3390/ijms241311179
Yura Y, Hamada M. Outline of Salivary Gland Pathogenesis of Sjögren’s Syndrome and Current Therapeutic Approaches. International Journal of Molecular Sciences. 2023; 24(13):11179. https://doi.org/10.3390/ijms241311179
Chicago/Turabian StyleYura, Yoshiaki, and Masakazu Hamada. 2023. "Outline of Salivary Gland Pathogenesis of Sjögren’s Syndrome and Current Therapeutic Approaches" International Journal of Molecular Sciences 24, no. 13: 11179. https://doi.org/10.3390/ijms241311179