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Psoriatic Arthritis: Pathogenesis and Targeted Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 13352

Special Issue Editor


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Guest Editor
Department of Rheumatology, Hospital Clinic of Barcelona, 08036 Barcelona, Spain
Interests: synovial immunopathology; biomarkers (clinical, serum and synovial tissue) diagnostic and prognostics - response to biological therapies); cytokines in biofluids and synovial tissue; lipidomics comparing psoriatic arthritis and rheumatoid arthritis; epigenomics (DNA methylation) related with disease activity and prognosis; genomics in psoriatic arthritis and rheumatoid arthritis

Special Issue Information

Dear Colleagues,

Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease that usually involves the skin and several musculoskeletal sites (joint, enthesis, and axial skeleton), and can also extend to the eye (uveitis) and the bowel (bowel inflammatory disease).  Furthermore, patients with PsA also show an increase in the prevalence of classical (T2 diabetes, hypertension, metabolic syndrome, obesity) and non-classical (systemic inflammation) cardiovascular risk factors, leading to a rise in morbidity and mortality.

Advances in basic and clinical research in the last two decades have improved our understanding of pathogenesis and helped the development of targeted therapies that provide better control of the disease and improve patients’ quality of life. Genomic and immunological studies in biofluids and synovial tissue of PsA patients have demonstrated two main immune-inflammatory pathways in PsA: TNFalfa and IL-23/IL-17. However, while skin has a higher expression of the IL-23/IL-17-related gene, in synovial tissue, there is higher TNFalfa-related gene expression. This discordance in cytokine expression among different tissues explains the differential therapeutic response between skin and joint to those cytokine inhibitors in PsA. Moreover, around 60% of PsA patients do not achieve significant clinical response (ACR50%) with the current targeted biological and synthetic therapies.

Therefore, addressing clinical heterogeneity and tissue pathogenesis diversity is one important step to better understand the molecular pathways resulting in different PsA endotypes. Finally, the definition of endotypes will inform therapy choice.

This Special Issue focused in “Psoriatic Arthritis: Pathogenesis and Targeted Therapies” will welcome revisions and original articles aiming to understand the link between cellular and molecular expression patterns and clinical heterogeneity, including the response to distinct targeted therapies in PsA. Some suggestions are:

  • Transcriptomic, proteomic, or single-cell–RNAseq analysis of the different tissues involved in PsA to gain insights on their molecular diversity and potentially reveal new targets;
  • Cytokine expression patterns (at the protein and mRNA level) in biofluids and/or involved tissues and its association with response to therapy;
  • Epigenetic (DNA methylation, mirRNA), lipidomics, and other -omic techniques looking at differences of translational/clinical relevance between PsA and rheumatoid arthritis or undifferentiated arthritis;
  • Other suggested articles related to the topic.

Dr. Juan D. Cañete
Guest Editor

Manuscript Submission Information

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Keywords

  • psoriatic arthritis
  • targeted therapies
  • rheumatoid arthritis
  • epigenetic

Published Papers (3 papers)

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Review

22 pages, 995 KiB  
Review
Targeted Therapies in Psoriatic Arthritis—An Update
by Sonia Sundanum, Carl Orr and Douglas Veale
Int. J. Mol. Sci. 2023, 24(7), 6384; https://doi.org/10.3390/ijms24076384 - 28 Mar 2023
Cited by 6 | Viewed by 2121
Abstract
Psoriatic arthritis (PsA) is a systemic inflammatory condition characterised by multiple clinical manifestations. Over the last decade, significant progress has been made in understanding the pathobiology of the disease. An expanded set of targeted therapies have emerged and have shown efficacy in PsA. [...] Read more.
Psoriatic arthritis (PsA) is a systemic inflammatory condition characterised by multiple clinical manifestations. Over the last decade, significant progress has been made in understanding the pathobiology of the disease. An expanded set of targeted therapies have emerged and have shown efficacy in PsA. Nevertheless, there is still a substantial subset of patients who experience no response or only a partial response to currently licensed therapies. The heterogeneous nature of the disease, together with a varying level of severity at presentation and disease activity during follow-up, brings tremendous challenges to devising management strategies. While there are certain pathophysiological similarities between PsA and rheumatoid arthritis (RA), it has become clear that there are discriminating features between these two conditions at the clinical, cellular, and molecular levels. However, there is a degree of overlap in the clinical approach when treating both PsA and RA, given that many biological and targeted therapies have proven efficacy for both pathologies. With an increasing understanding of the relevance of the IL-23/IL-17 axis in PsA, pharmacological agents blocking this pathway have provided promising possibilities for patients with PsA. Full article
(This article belongs to the Special Issue Psoriatic Arthritis: Pathogenesis and Targeted Therapies)
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22 pages, 3212 KiB  
Review
Evaluation of the Synovial Effects of Biological and Targeted Synthetic DMARDs in Patients with Psoriatic Arthritis: A Systematic Literature Review and Meta-Analysis
by Maria Sofia Ciliento, Veronica Venturelli, Natale Schettini, Riccardo Bertola, Carlo Garaffoni, Giovanni Lanza, Roberta Gafà, Alessandro Borghi, Monica Corazza, Alen Zabotti, Sonia Missiroli, Caterina Boncompagni, Simone Patergnani, Mariasole Perrone, Carlotta Giorgi, Paolo Pinton, Marcello Govoni, Carlo Alberto Scirè, Alessandra Bortoluzzi and Ettore Silvagni
Int. J. Mol. Sci. 2023, 24(5), 5006; https://doi.org/10.3390/ijms24055006 - 05 Mar 2023
Cited by 2 | Viewed by 2352
Abstract
The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to [...] Read more.
The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature. Full article
(This article belongs to the Special Issue Psoriatic Arthritis: Pathogenesis and Targeted Therapies)
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23 pages, 1618 KiB  
Review
Psoriatic Arthritis: Pathogenesis and Targeted Therapies
by Ana Belén Azuaga, Julio Ramírez and Juan D. Cañete
Int. J. Mol. Sci. 2023, 24(5), 4901; https://doi.org/10.3390/ijms24054901 - 03 Mar 2023
Cited by 16 | Viewed by 8328
Abstract
Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated with uveitis and inflammatory bowel disease (Crohn’s disease and ulcerative colitis). To capture these manifestations [...] Read more.
Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated with uveitis and inflammatory bowel disease (Crohn’s disease and ulcerative colitis). To capture these manifestations as well as the associated comorbidities, and to recognize their underlining common pathogenesis, the name of psoriatic disease was coined. The pathogenesis of PsA is complex and multifaceted, with an interplay of genetic predisposition, triggering environmental factors, and activation of the innate and adaptive immune system, although autoinflammation has also been implicated. Research has identified several immune-inflammatory pathways defined by cytokines (IL-23/IL-17, TNF), leading to the development of efficacious therapeutic targets. However, heterogeneous responses to these drugs occur in different patients and in the different tissues involved, resulting in a challenge to the global management of the disease. Therefore, more translational research is necessary in order to identify new targets and improve current disease outcomes. Hopefully, this may become a reality through the integration of different omics technologies that allow better understanding of the relevant cellular and molecular players of the different tissues and manifestations of the disease. In this narrative review, we aim to provide an updated overview of the pathophysiology, including the latest findings from multiomics studies, and to describe current targeted therapies. Full article
(This article belongs to the Special Issue Psoriatic Arthritis: Pathogenesis and Targeted Therapies)
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