Background Semaphorin 3A (sema 3A), is now recognized as a potent immuno-regulator during all stages of the immune response. Sema 3A expression has been recognized on T regulatory cells as a suppressive marker, contributing to the regulatory properties of these cells . Decreased expression of sema 3A and correlation with disease activity has been reported in rheumatoid arthritis patients and systemic lupus erthematosus (SLE) [2,3]. The expression of sema 3A hasn't been evaluated in systemic sclerosis (SSc) thus far.
Objectives To compare sema 3A serum levels in patients with SSc to SLE patients (disease control) and healthy controls.
To measure expression of sema 3A in whole blood and on regulatory T-cells and correlate it with demographic, clinical and laboratory parameters in SSc.
Methods 27 SSc patients were evaluated for demographics, clinical manifestations, routine laboratory results, serum autoantibodies, sema 3A serum levels (measured by commercial ELISA kit) and expression on regulatory T cells CD 4+ CD 25 bright (by flow cytometry), nailfold videocapillaroscopy patterns, pulmonary function tests, echocardiograms, high resolution lung CT scans, modified Rodnan skin score (mRSS), Medsger disease severity scale and Valentini activity index. Sema 3A serum levels were also evaluated in 42 sex and age matched SLE patients (disease control) and 28 healthy controls.
Results Twenty seven SSc patients (10 with diffuse cutaneous disease) were evaluated and compared with healthy controls and disease controls (SLE). Sema 3A expression in SSc patients was lower than healthy controls as measured by flow cytometry on regulatory T cells 61.7% ±15.7 vs. 88.7% ±3.6 (p<0.001). Sema 3A concentration in serum of SSc was lower than healthy controls also when measured by ELISA 14.4 ng/ml ±5.6 vs. 27.1 ng/ml ±8.4 (p<0.001) and comparable to SLE. Sema 3A levels negatively correlated with disease duration r = -0.4, p value=0.036. Anti scl-70 antibodies were associated with a lower level of sema 3A (difference between means of 3.8 ng/ml, p value=0.0293).
Conclusions The expression of sema 3A is reduced in SSc patients and inversely correlates with disease duration and scl-70 antibodies production. Sema 3A role in the prevention of autoimmunity has been suggested to be mediated by its effect on regulatory T cells. Regulatory T cells have been reported in the literature to be reduced and functionally impaired in SSc. Our finding of low levels of sema 3A in SSc correlating with disease duration is in line with the literature and may serve to explain the impairment regulatory T cells in SSc. Further studies are needed to assess the cause-effect relations between sema 3A, regulatory T cells and disease progression in SSc.
Vadasz Z, Toubi E. Semaphorins: Their Dual Role in Regulating Immune-Mediated Diseases.Clin Rev Allergy Immunol. 2013 Feb 9. [Epub ahead of print].
Takagawa S, Nakamura F, Kumagai K, et al. Decreased semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis.BMC Musculoskelet Disord. 2013;14:40.
Vadasz Z, Haj T, Halasz K, et al. Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus.Arthritis Res Ther. 2012 14;14(3):R146.
Disclosure of Interest None declared
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