Background/Purpose:  Vascular involvement has a major impact on  the pathogenesis   of Systemic sclerosis (SSc) and there is evidence that microvascular damage with endothelial cell activation  may direct  the phenotypic presentation of the disease. Endothelial Vinculin has a crucial regulatory role  during angiogenesis(1). Villano et al., showed that expression of vinculin was significantly higher in endothelial cells challenged with the sera of SSc pts  than  endothelial cells treated with sera from healthy controls(2). Hence, the dysregulated vinculin expression may add to defective angiogenic processes already  present  in SSc. We hypothesize that over- expression of Vinculin in SSc may trigger anti-vinculin antibodies (abs) which may contribute to vasculopathic features in SSc. Objective: To measure the levels of anti-Vinculin antibodies in serum of scleroderma patients, in comparison to Healthy controls and to correlate their levels with SSc related outcome measures. Methods: Serum samples from 72 SSc patients meeting the ACR/EULAR 2013  SSc criteria and 50 healthy controls  were recruited. Serum levels of anti-vinculin antibodies were determined by ELISA. Clinical data were obtained from charts for statistical correlations.

Results: The 72 SSc pts’ characteristics: 32(48.4%) diffuse SSc , mean age: 56.4(SD ± 18); active skin ulcers 17(25.7%), mean GIT 2.0 was 0.373; interstitial lung disease (ILD)  40 (55%)pts; Pulmonary artery hypertension (PAH)  23(31%)pts. Mean anti-Vinculin levels  were significantly higher in SSc pts (1 ug/ml SD ±1 ) than in healthy controls (0.6 ug/ml SD ± 0.6) p < 0.01. Figure 1. In the linear regression models, BMI was a significant predictor of higher anti-vinculin (p<0.005). PAH trended to predict higher anti-vinculin (p=0.052). The lack of usual statistical significance may be due to low statistical power of (post-hoc power=0.44) and might be detectable in a larger sample. Neither Skin ulcer (p=0.752) nor  Raynaud’s  severity by visual analogue scale (p= 0.591) predicted higher anti-vinculin antibodies.

Conclusion: We report for the first time, higher levels  of anti-vinculin antibodies( a potential  marker of vascular involvement) in SSc patients than controls and a trend to correlation with PAH.  Further research is warranted on more SSc patients to evaluate the role of anti-vinculin antibodies as markers of vascular involvement(i.e., PAH) and to  identify  their role in the pathogenesis of SSc /SSc-PAH.

References (1)Deroanne CF, Colige AC, Nusgens BV, Lapiere CM: Modulation of expression and assembly of vinculin during in vitro fibrillar collagen induced angiogenesis and its reversal. Exp Cell Res 1996, 224:215-223. (2)Villano et al. Systemic sclerosis sera affect fibrillin-1 deposition by dermal blood microvascular endothelial cells: therapeutic implications of cyclophosphamideArthritis Research & Therapy 2013, 15:R90

Figure 1: showing the Levels of antivinculin antibodies in SSc and healthy controls.