A6.14 Semaphorin 3A, an immunoregulator and potential biomarker for disease severity in systemic sclerosis

Introduction Semaphorin 3A (sema3A) plays a regulatory role in immune responses, mainly affecting the activation of regulatory T cells. It has been found to correlate with disease activity in rheumatoid arthritis and systemic lupus erythematosus (SLE). Aim To investigate the expression of sema3A in patients with systemic sclerosis (SSc) compared to healthy controls and SLE disease controls and to correlate its expression with clinical characteristics. Methods 27 SSc patients, 42 SLE patients and 18 healthy controls were enrolled. Serum level of sema3A was measured by ELISA and expression of sema3A on regulatory T cells was evaluated by FACS analysis. SSc patients were evaluated for demographics, clinical manifestations, routine laboratory results, nailfold videocapillaroscopy patterns, pulmonary function tests, echocardiograms, modified Rodnan skin score (mRSS) and disease activity and severity scores. Results Serum levels of semaphorin 3A were lower in SSc compared to healthy controls 14.38 ± 5.7 ng/ml vs. 27.14 ± 8.4 ng/ml, p < 0.0001 and similar to SLE 15.7 ± 4.3 ng/ml. The expression of semaphorin 3A on regulatory T cells was also lower in SSc compared to healthy controls 61.7 ± 15.7% vs. 88.7 ± 3. 7% (p < 0.0001). Semaphorin 3A serum level inversely correlated with the duration of disease; r = -0.4, p = 0.036 and with low C4 level r = 0.66 p = 0.026. SCL-70 antibody positivity was associated with a lower semaphorin 3A level in serum (difference in mean of 3.44 p = 0.06). Conclusion Sema3A expression is low in SSc serum and more specifically on regulatory T cells. This may help explain the reduced activation of regulatory T cells in SSc, contributes to our understanding of the pathogenesis of the disease and may serve as a future target for treatment.