Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation, vasculopathy, and fibrosis, with B cell activation playing a critical role in its pathogenesis [1]. Interleukin-40 (IL-40), primarily produced by activated B cells, has been implicated as a potential biomarker in autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, due to its role in inflammation and humoral immune responses [2]. The elevated expression of B cell-related molecules like IL-40 and BAFF in SSc suggests their involvement in fibrosis and disease progression.

Objectives: This study aims to evaluate the role of IL-40 in the pathogenesis of systemic sclerosis by assessing its relationship with clinical findings and disease activity and investigating the correlation between IL-40 levels and immunosuppressive therapies.

Methods: This study recruited 47 systemic sclerosis (SSc) patients meeting the 2013 ACR/EULAR classification criteria, categorized into three subgroups based on disease activity and immunosuppressive therapy status, alongside 30 age- and sex-matched healthy controls. Clinical assessments included symptoms, serological markers, and immunosuppressive therapy status, with IL-40 serum levels measured via ELISA from stored samples.

Results: This study evaluated 47 systemic sclerosis (SSc) patients, primarily female (93.6%), with a mean age of 44.7 years and median disease duration of 9 years. Patients were classified into diffuse SSc (44.7%), limited SSc (46.8%), and overlap syndrome (8.5%). Common manifestations included Raynaud phenomenon (93.6%), sclerodactyly (89.4%), interstitial lung disease (46.8%), and esophageal dysphagia (46.8%). Serologically, anti-nuclear antibody positivity was observed in 89.4%, anti-topoisomerase I in 61.7%, and anti-centromere antibody in 19.1%. Patients were categorized into three subgroups based on disease activity and immunosuppressive therapy status. The patients currently receiving immunosuppressive therapies included those on mycophenolate mofetil (n=13), glucocorticoids (n=9), azathioprine (n=2), cyclophosphamide (n=1), and rituximab (n=1). These are given in Table 1. IL-40 levels differed significantly across clinical groups. Patients receiving immunosuppressive therapy (IS) had lower IL-40 levels than those without IS (0.54 vs. 1.15 ng/ml, p=0.001). IL-40 levels were higher in active disease without IS (1.63 ng/ml) compared to remission without IS (0.98 ng/ml, p=0.031). IL-40 levels in healthy controls were comparable to those in remission without IS. These are given in Figure 1. These findings suggest IL-40 as a potential biomarker for SSc activity, reflecting the interplay of disease activity and immunosuppressive therapy effects.

Conclusion: Our study found that IL-40 levels were significantly lower in SSc patients receiving immunosuppressive therapy compared to those not receiving such treatment and healthy controls. Additionally, IL-40 levels were elevated in patients with active disease who were not on immunosuppressive therapy. These findings suggest that IL-40 may serve as a biomarker for assessing disease activity in SSc and could also provide insights into the effectiveness of immunosuppressive therapies targeting B cells.

REFERENCES: [1] Denton CP, Khanna D. Systemic sclerosis. The Lancet . 2017;390:1685–99. doi: 10.1016/S0140-6736(17)30933-9.

[2] Catalan-Dibene J, Vazquez MI, Luu VP, et al. Identification of IL-40, a Novel B Cell-Associated Cytokine. J Immunol . 2017;199:3326–35. doi: 10.4049/jimmunol.1700534.

Figure 1.

Comparison of IL-40 Levels Among different SSc patients and healthy group.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.