The Potential Utility of Salivary and Tear Proteomics to Discriminate Sjögren’s Disease from Non-Sjögren’s Sicca
Abstract
:1. Introduction
2. Classification Criteria for SjD
3. Salivary Protein Profiling
3.1. Methodological Approaches Used for Saliva Proteomics
3.1.1. Gel Electrophoresis
3.1.2. Mass Spectrometry
3.2. Novel Salivary Biomarkers in Sjögren’s Disease
3.2.1. Identification of Salivary Biomarkers Using Database Studies
3.2.2. Identification of Salivary Biomarkers Using Western Blotting
3.2.3. Identification of Salivary Biomarkers Using Mass Spectrometry
4. Tear Protein Profiling
4.1. Methodological Approaches Used for Tear Proteomics
4.1.1. MALDI-TOF
4.1.2. MALDI-TOF in Combination with SELDI-TOF
4.1.3. SELDI-TOF
4.1.4. LC-MS/MS
4.2. Novel Tear Biomarkers in SjD
4.2.1. Liquid Chromatography–Tandem Mass Spectrometry Studies
4.2.2. Two-Dimensional Nano-Liquid Chromatography–Tandem Mass Spectrometry
4.2.3. Shotgun Proteomic Analysis
4.2.4. Cathepsin S Tear Film Analysis
5. Conclusions
Funding
Conflicts of Interest
References
- Ramos-Casals, M.; Brito-Zerón, P.; Sisó-Almirall, A.; Bosch, X. Primary Sjögren syndrome. Praxis (Bern. 1994) 2012, 101, 1565–1571. [Google Scholar] [CrossRef] [PubMed]
- Fox, R.I.; Fox, C.M.; Gottenberg, J.E.; Dörner, T. Treatment of Sjögren’s syndrome: Current therapy and future directions. Rheumatology 2021, 60, 2066–2074. [Google Scholar] [CrossRef] [PubMed]
- Theander, E.; Henriksson, G.; Ljungberg, O.; Mandl, T.; Manthorpe, R.; Jacobsson, L.T. Lymphoma and other malignancies in primary Sjögren’s syndrome: A cohort study on cancer incidence and lymphoma predictors. Ann. Rheum. Dis. 2016, 65, 796–803. [Google Scholar] [CrossRef] [PubMed]
- Peluso, G.; De Santis, M.; Inzitari, R.; Fanali, C.; Cabras, T.; Messana, I.; Castagnola, M.; Ferraccioli, G.F. Proteomic study of salivary peptides and proteins in patients with Sjögren’s syndrome before and after pilocarpine treatment. Arthritis Rheum. 2007, 56, 2216–2222. [Google Scholar] [CrossRef] [PubMed]
- Ramos-Casals, M.; Tzioufas, A.G.; Stone, J.H.; Sisó, A.; Bosch, X. Treatment of primary Sjögren syndrome: A systematic review. JAMA 2010, 304, 452–460. [Google Scholar] [CrossRef] [PubMed]
- Mansour, K.; Leonhardt, C.J.; Kalk, W.W.; Bootsma, H.; Bruin, K.J.; Blanksma, L.J. Lacrimal punctum occlusion in the treatment of severe keratoconjunctivitis Sicca caused by Sjögren syndrome: A uniocular evaluation. Cornea 2007, 26, 147–150. [Google Scholar] [CrossRef] [PubMed]
- Das, N.; Menon, N.G.; de Almeida, L.G.N.; Woods, P.S.; Heynen, M.L.; Jay, G.D.; Caffery, B.; Jones, L.; Krawetz, R.; Schmidt, T.A.; et al. Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients. Front. Pharmacol. 2021, 12, 787193. [Google Scholar] [CrossRef]
- Pasoto, S.G.; Adriano de Oliveira Martins, V.; Bonfa, E. Sjögren’s syndrome and systemic lupus erythematosus: Links and risks. Open Access Rheumatol. 2019, 11, 33–45. [Google Scholar] [CrossRef]
- Farris, A.D.; Gross, J.K.; Hanas, J.S.; Harley, J.B. Genes for murine Y1 and Y3 Ro RNAs have class 3 RNA polymerase III promoter structures and are unlinked on mouse chromosome 6. Gene 1996, 174, 35–42. [Google Scholar] [CrossRef]
- Wenzel, J.; Gerdsen, R.; Uerlich, M.; Bauer, R.; Bieber, T.; Boehm, I. Antibodies targeting extractable nuclear antigens: Historical development and current knowledge. Br. J. Dermatol. 2001, 145, 859–867. [Google Scholar] [CrossRef]
- Ben-Chetrit, E. Target antigens of the SSA/Ro and SSB/La system. Am. J. Reprod. Immunol. 1992, 28, 256–258. [Google Scholar] [CrossRef] [PubMed]
- Katsiougiannis, S.; Wong, D.T. The Proteomics of Saliva in Sjögren’s Syndrome. Rheum. Dis. Clin. North Am. 2016, 42, 449–456. [Google Scholar] [CrossRef] [PubMed]
- 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] [PubMed]
- 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] [PubMed]
- Steiner, G.; Van Hoovels, L.; Csige, D.; Gatto, M.; Iagnocco, A.; Szekanecz, Z. Should ACR/EULAR criteria be revised changing the RF and ACPA scores? Autoimmun. Rev. 2023, 2023, 103421. [Google Scholar] [CrossRef] [PubMed]
- Daniels, T.E.; Shiboski, C.; Shiboski, S.; Lanfranchi, H.; Yi, D.; Schiødt, M.; Umehara, H.; Sugai, S.; Challacombe, S.; Greenspan, J.S.; et al. An Early View of the International Sjögren’s Syndrome Registry. Arthritis Rheum. 2009, 61, 711. [Google Scholar] [CrossRef] [PubMed]
- 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]
- 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]
- Hu, S.; Loo, J.A.; Wong, D.T. Human saliva proteome analysis. Ann. N. Y. Acad. Sci. 2007, 1098, 323–329. [Google Scholar] [CrossRef]
- Hu, S.; Jiang, J.; Wong, D.T. Proteomic analysis of saliva: 2D gel electrophoresis, LC-MS/MS, and Western blotting. Methods Mol. Biol. 2010, 666, 31–41. [Google Scholar]
- Al Kawas, S.; Rahim, Z.H.; Ferguson, D.B. Potential uses of human salivary protein and peptide analysis in the diagnosis of disease. Arch. Oral Biol. 2012, 57, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Hu, S.; Vissink, A.; Arellano, M.; Roozendaal, C.; Zhou, H.; Kallenberg, C.G.; Wong, D.T. Identification of autoantibody biomarkers for primary Sjögren’s syndrome using protein microarrays. Proteomics 2011, 11, 1499–1507. [Google Scholar] [CrossRef] [PubMed]
- Baldini, C.; Giusti, L.; Ciregia, F.; Da Valle, Y.; Giacomelli, C.; Donadio, E.; Sernissi, F.; Bazzichi, L.; Giannaccini, G.; Bombardieri, S.; et al. Proteomic analysis of saliva: A unique tool to distinguish primary Sjögren’s syndrome from secondary Sjögren’s syndrome and other sicca syndromes. Arthritis Res. Ther. 2011, 13, R194. [Google Scholar] [CrossRef] [PubMed]
- Hu, S.; Xie, Y.; Ramachandran, P.; Ogorzalek Loo, R.R.; Li, Y.; Loo, J.A.; Wong, D.T. Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry. Proteomics 2005, 5, 1714–1728. [Google Scholar] [CrossRef] [PubMed]
- Katsani, K.R.; Sakellari, D. Saliva proteomics updates in biomedicine. J. Biol. Res. 2019, 26, 17. [Google Scholar] [CrossRef] [PubMed]
- Aqrawi, L.A.; Galtung, H.K.; Guerreiro, E.M.; Øvstebø, R.; Thiede, B.; Utheim, T.P.; Chen, X.; Utheim, Ø.A.; Palm, Ø.; Skarstein, K.; et al. Proteomic and histopathological characterisation of sicca subjects and primary Sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers. Arthritis Res. Ther. 2019, 21, 181. [Google Scholar] [CrossRef] [PubMed]
- Gottenberg, J.E.; Seror, R.; Miceli-Richard, C.; Benessiano, J.; Devauchelle-Pensec, V.; Dieude, P.; Dubost, J.J.; Fauchais, A.L.; Goeb, V.; Hachulla, E.; et al. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren’s syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS ONE 2013, 8, e59868. [Google Scholar] [CrossRef]
- Pawar, R.D.; Goilav, B.; Xia, Y.; Zhuang, H.; Herlitz, L.; Reeves, W.H.; Putterman, C. Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin. Clin. Immunol. 2014, 154, 49–65. [Google Scholar] [CrossRef]
- Baldini, C.; Cecchettini, A.; Gallo, A.; Bombardieri, S. Updates on Sjögren’s syndrome: From proteomics to protein biomarkers. Expert. Rev. Proteom. 2017, 14, 491–498. [Google Scholar] [CrossRef]
- Sembler-Møller, M.L.; Belstrøm, D.; Locht, H.; Pedersen, A.M.L. Proteomics of saliva, plasma, and salivary gland tissue in Sjögren’s syndrome and non-Sjögren patients identify novel biomarker candidates. J. Proteom. 2020, 225, 103877. [Google Scholar] [CrossRef]
- Aqrawi, L.A.; Galtung, H.K.; Vestad, B.; Øvstebø, R.; Thiede, B.; Rusthen, S.; Young, A.; Guerreiro, E.M.; Utheim, T.P.; Chen, X.; et al. Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis. Arthritis Res. Ther. 2017, 19, 14. [Google Scholar] [CrossRef]
- Aqrawi, L.A.; Jensen, J.L.; Øijordsbakken, G.; Ruus, A.K.; Nygård, S.; Holden, M.; Jonsson, R.; Galtung, H.K.; Skarstein, K. Signalling pathways identified in salivary glands from primary Sjögren’s syndrome patients reveal enhanced adipose tissue development. Autoimmunity 2018, 51, 135–146. [Google Scholar] [CrossRef]
- Ponzini, E.; Ami, D.; Duse, A.; Santambrogio, C.; De Palma, A.; Di Silvestre, D.; Mauri, P.; Pezzoli, F.; Natalello, A.; Tavazzi, S.; et al. Single-Tear Proteomics: A Feasible Approach to Precision Medicine. Int. J. Mol. Sci. 2021, 22, 10750. [Google Scholar] [CrossRef]
- Soria, J.; Acera, A.; Merayo, L.J.; Durán, J.A.; González, N.; Rodriguez, S.; Bistolas, N.; Schumacher, S.; Bier, F.F.; Peter, H.; et al. Tear proteome analysis in ocular surface diseases using label-free LC-MS/MS and multiplexed-microarray biomarker validation. Sci. Rep. 2017, 7, 17478. [Google Scholar] [CrossRef] [PubMed]
- González, I.I.N.; Soria, J.; Duran, J.; Santamaría, A.; Santamaría, A.; Elortza, F.; Suárez, T. Human tear peptide/protein profiling study of ocular surface diseases by SPE-MALDI-TOF mass spectrometry analyses. Eupa Open Proteom. 2014, 3, 206–215. [Google Scholar] [CrossRef]
- Boehm, N.; Funke, S.; Wiegand, M.; Wehrwein, N.; Pfeiffer, N.; Grus, F.H. Alterations in the tear proteome of dry eye patients--a matter of the clinical phenotype. Investig. Ophthalmol. Vis. Sci. 2013, 54, 2385–2392. [Google Scholar] [CrossRef] [PubMed]
- Beckman, K.A.; Luchs, J.; Milner, M.S. Making the diagnosis of Sjögren’s syndrome in patients with dry eye. Clin. Ophthalmol. 2016, 10, 43–53. [Google Scholar] [PubMed]
- Grus, F.H.; Podust, V.N.; Bruns, K.; Lackner, K.; Fu, S.; Dalmasso, E.A.; Wirthlin, A.; Pfeiffer, N. SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye. Investig. Ophthalmol. Vis. Sci. 2005, 46, 863–876. [Google Scholar] [CrossRef] [PubMed]
- Tomosugi, N.; Kitagawa, K.; Takahashi, N.; Sugai, S.; Ishikawa, I. Diagnostic potential of tear proteomic patterns in Sjögren’s syndrome. J. Proteome Res. 2005, 4, 820–825. [Google Scholar] [CrossRef] [PubMed]
- Pitt, J.J. Principles and applications of liquid chromatography-mass spectrometry in clinical biochemistry. Clin. Biochem. Rev. 2009, 30, 19–34. [Google Scholar]
- Li, B.; Sheng, M.; Li, J.; Yan, G.; Lin, A.; Li, M.; Wang, W.; Chen, Y. Tear proteomic analysis of Sjögren syndrome patients with dry eye syndrome by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry. Sci. Rep. 2014, 4, 5772. [Google Scholar] [CrossRef] [PubMed]
- Zhou, L.; Zhao, S.Z.; Koh, S.K.; Chen, L.; Vaz, C.; Tanavde, V.; Li, X.R.; Beuerman, R.W. In-depth analysis of the human tear proteome. J. Proteom. 2012, 75, 3877–3885. [Google Scholar] [CrossRef] [PubMed]
- Kuo, M.T.; Fang, P.C.; Chao, T.L.; Chen, A.; Lai, Y.H.; Huang, Y.T.; Tseng, C.Y. Tear Proteomics Approach to Monitoring Sjögren Syndrome or Dry Eye Disease. Int. J. Mol. Sci. 2019, 20, 1932. [Google Scholar] [CrossRef] [PubMed]
- Das, N.; Schmidt, T.A.; Krawetz, R.J.; Dufour, A. Proteoglycan 4: From Mere Lubricant to Regulator of Tissue Homeostasis and Inflammation: Does proteoglycan 4 have the ability to buffer the inflammatory response? Bioessays 2019, 41, e1800166. [Google Scholar] [CrossRef] [PubMed]
- Saegusa, K.; Ishimaru, N.; Yanagi, K.; Arakaki, R.; Ogawa, K.; Saito, I.; Katunuma, N.; Hayashi, Y. Cathepsin S Inhibitor Prevents Autoantigen Presentation and Autoimmunity. J. Clin. Investig. 2002, 110, 361–369. [Google Scholar] [CrossRef]
- Klinngam, W.; Janga, S.R.; Lee, C.; Ju, Y.; Yarber, F.; Shah, M.; Guo, H.; Wang, D.; MacKay, J.A.; Edman, M.C.; et al. Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sjögren’s Syndrome. Sci. Rep. 2019, 9, 9559. [Google Scholar] [CrossRef]
- Klinngam, W.; Fu, R.; Janga, S.R.; Edman, M.C.; Hamm-Alvarez, S.F. Cathepsin S Alters the Expression of Pro-Inflammatory Cytokines and MMP-9, Partially through Protease-Activated Receptor-2, in Human Corneal Epithelial Cells. Int. J. Mol. Sci. 2018, 19, 3530. [Google Scholar] [CrossRef]
- Edman, M.C.; Janga, S.R.; Meng, Z.; Bechtold, M.; Chen, A.F.; Kim, C.; Naman, L.; Sarma, A.; Teekappanavar, N.; Kim, A.Y.; et al. Increased cathepsin s activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in sjögren’s syndrome patients. Sci. Rep. 2018, 8, 11044. [Google Scholar] [CrossRef]
- Renduchintala, K.; Whitt, S.E.; Janga, S.; Shah, M.; Heur, M.; Irvine, J.; Arkfeld, D.; Mack, W.J.; Stohl, W.; Hamm-Alvarez, S.F. Tear-Derived Cathepsin S Activity as a Novel Diagnostic Marker for Sjögren’s Syndrome. Investig. Ophthalmol. Vis. Sci. 2012, 53, 4240. [Google Scholar]
- Hargreaves, P.; Theron, M.; Kolb, F.; Manchester, M.; Reis, B.; Tiaden, A.; Kyburz, D.; Manigold, T. Inhibition of Cathepsin S Leads to Suppression of SS-a/SS-B Specific T Cells from Patients with Primary Sjøgren Syndrome. In Arthritis & Rheumatology; Wiley: Hoboken, NJ, USA, 2018; Volume 70. [Google Scholar]
- Bentley, D.; Fisher, B.A.; Barone, F.; Kolb, F.A.; Attley, G. A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study on the Effects of a Cathepsin S Inhibitor in Primary Sjögren’s Syndrome. Rheumatology 2023, 62, 3644–3653. [Google Scholar] [CrossRef]
- Hargreaves, P.; Daoudlarian, D.; Theron, M.; Kolb, F.A.; Young, M.M.; Reis, B.; Tiaden, A.; Bannert, B.; Kyburz, D. Differential effects of specific cathepsin S inhibition in biocompartments from patients with primary Sjögren syndrome. Arthritis Res. Ther. 2019, 21, 175. [Google Scholar] [CrossRef] [PubMed]
Items | I. Ocular symptoms (at least one present) |
|
II. Oral symptoms (at least one present) |
| |
III. Objective evidence of dry eyes |
| |
IV. Objective evidence of salivary gland involvement (at least one present) |
| |
V. Histopathological evidence |
| |
VI. Serological abnormality |
| |
Rules for classification | 1. Absence of AECG exclusion criteria a 2. Four items must be present for classification; one of these items must be either V or VI |
Weight/Score | ||
---|---|---|
Items |
| 3 |
| 3 | |
| 1 | |
| 1 | |
| 1 | |
Rules for classification | 1. Absence of exclusion criteria a 2. Has at least one symptom of oral or ocular dryness, or ESSDAI ≥ 1 3. Weight/score of ≥4 |
Experimental Method | Differentially Expressed Proteins Identified |
---|---|
Mass spectrometry in tandem with Western blotting and enzyme-linked immunosorbent assay (ELISA) | ↑ α-Enolase, IGKC, psoriasin (protein S100-A7), calgranulin B (protein S100-A9), E-FABP, beta-2-microglobulin, ↓ α-Amylase precursor, carbonic anhydrase VI, G3PDH, PIP, SPLUNC-2 |
Liquid chromatography–tandem mass spectrometry results were analyzed with DAVID and the Functional Enrichment Analysis Tool (FunRich) | ↑ Secreted Ly-6/uPAR-related protein 1, beta-2-microglobulin, clusterin |
Liquid chromatography and tandem mass spectrometry a | ↑ Neutrophil elastase, calreticulin, tripartite motif-containing protein 29 |
Liquid chromatography and tandem mass spectrometry | ↑ DJ-1/Parkinson disease protein 7, cathepsin G, neutrophil elastase, lactotransferrin, azurocidin, cystatin-SA, calpastatin, proteinase 3/myeloblastin, alpha-1-antitrypsin, transmembrane protease serine 11D |
Experimental Method | Differentially Expressed Proteins Identified |
---|---|
Liquid chromatography–tandem mass spectrometry | ↑ MMP-9:lactoferrin ↓ Lipocalin-1, lacritin, prolactin-inducible protein |
Liquid chromatography–tandem mass spectrometry in conjunction with size-exclusion chromatography and sole LC-MS | ↑ Neutrophil gelatinase-associated lipocalin, CPNE1, PRDX3 |
Two-dimensional nanoliquid chromatography–tandem mass spectrometry | ↑
CDNA FLJ78387, annexin A2 isoform 1, serotransferrin precursor, keratin 4, protein S100-A9, mucin-5AC precursor, annexin A1, keratin type I cytoskeletal 10, keratin type II cytoskeletal 1, protein S100-A8, complement C3 precursor, actin, ↓ Growth-inhibiting protein 12, lipocalin-1 precursor, prolactin-inducible protein precursor, IGHA1 protein, polymeric immunoglobulin receptor precursor, extracellular glycoprotein lacritin precursor, lysozyme C precursor, proline-rich protein 4 precursor, cystatin-S precursor, keratin type II cytoskeletal 5 |
High-performance liquid chromatography and mass spectroscopy | ↑
Matrix metalloproteinase-9, cystatin-D, neutrophil collagenase, cystatin-C, cathepsin B, leukotriene A-4 hydrolase, prostasin ↓ Calpain-1, cytosolic non-specific dipeptidase, kininogen-1, alpha-2-antiplasmin, DJ-1/Parkinson disease protein 7, proteasome subunit alpha type-6, proteasome subunit alpha type-3, acylamino-acid-releasing enzyme, proteasome subunit type-2, cytosol aminopeptidase, phosphatidylethanolamine-binding protein, proteasome subunit beta type-8, leukocyte elastase inhibitor |
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George, C.T.; Kurien, B.T.; Scofield, R.H. The Potential Utility of Salivary and Tear Proteomics to Discriminate Sjögren’s Disease from Non-Sjögren’s Sicca. Int. J. Mol. Sci. 2023, 24, 17497. https://doi.org/10.3390/ijms242417497
George CT, Kurien BT, Scofield RH. The Potential Utility of Salivary and Tear Proteomics to Discriminate Sjögren’s Disease from Non-Sjögren’s Sicca. International Journal of Molecular Sciences. 2023; 24(24):17497. https://doi.org/10.3390/ijms242417497
Chicago/Turabian StyleGeorge, Christopher T., Biji T. Kurien, and R. Hal Scofield. 2023. "The Potential Utility of Salivary and Tear Proteomics to Discriminate Sjögren’s Disease from Non-Sjögren’s Sicca" International Journal of Molecular Sciences 24, no. 24: 17497. https://doi.org/10.3390/ijms242417497