PO:33:195 | Evaluation of prevalence and role of anti-endothelin type a-receptor and anti-angiotensin ii type 1-receptor antibodies in a cohort of systemic sclerosis patients

Clara Minerba¹, Sara Ferrigno¹, Antonella Grimaldi², Noemi Aprile³, Daniela Costanza², Laura Quarta², Maria Rita Ricciardi², Daniela Stasi³, Paola Conigliaro¹, Alberto Bergamini¹, Eugenio Quarta², Maria Sole Chimenti¹. | ¹U.O.C. Reumatologia, Dipartimento di Medicina dei Sistemi, Università di, Roma, Tor Vergata, Roma, Italy; ²U.O.S.D. Reumatologia, P.O. Vito Fazzi Lecce Italy; ³U.O.C. Patologia clinica e Microbiologia, P.O. Vito Fazzi Lecce Italy.

Background. Systemic sclerosis (SSc) is a systemic, autoimmune, heterogeneous disease, characterized by fibrosis and vasculopathy of skin and internal organs. Disease prognosis is mainly driven by autoantibody profile and specific organs involvement. The renin-angiotensin and endothelin systems have been implicated in the pathogenesis of vascular dysfunction. Antibodies (abs) against the angiotensin II type 1-receptor (AT1R) and the endothelin type A-receptor (ETAR) have been hypothesized to play a pathogenetic role in SSc, although their role in SSc remains unclear. Severe vascular disease manifestations have been associated with higher titers of anti-AT1R and anti-ETAR abs, which also appear to predict SSc-related mortality. Aim of the study was to estimate the prevalence of these autoabs in an SSc cohort and to evaluate their possible correlation with clinical and laboratory characteristics.

Materials and Methods. A cross-sectional monocentric study enrolling SSc patients was conducted. Demographic, clinical and laboratory data were collected and nailfold capillaroscopy was performed. Sera were tested by enzyme-linked immunosorbent assay for anti-AT1R and anti-ETAR abs, indirect immunofluorescence on Hep2 cells for anti-nuclear (ANA) abs, immunoblotting, fluorescent enzyme and chemiluminescence immunoassays for exctractable nuclear antigens (ENA) abs. Patients under anti-endothelin receptor antagonists were excluded. Categorical variables were compared using the chi-squared test, continuous variables were compared using t-test or Mann Whitney U test. Variables with statistical significance were tested in a multivariate regression model, corrected for selected confounders.

Results. A population of 80 SSc patients was enrolled. 6 patients resulted to be positive for both anti-ETAR and anti-AT1R abs, 8 patients only for anti-ETAR abs. Table 1 shows demographic and clinical data of the study population. Characteristics of patients anti-ETAR/AT1R abs positive were compared to patients negative for both the autoabs: anti-ETAR/AT1R abs positive patients resulted to have a significant higher prevalence of ischemic digital ulcers (IDU) (p=0.017). Patients positive for anti-ETAR/AT1R abs had a significant higher risk of having IDU independently from ongoing treatment with prostanoids (OR 5.7, 95%CI 1-33.26). Figure 1 shows the proportion of patients with IDU in the two groups. Patients positive for anti-ETAR/AT1R abs showed higher risk for presenting an early scleroderma pattern at the capillaroscopy rather than the other patterns, although the result did not reach the statistical significance (OR 4.5, 95%CI 0.4-49.6). Normal capillaroscopy was the reference group. Finally, patients under steroid treatment showed half-risk of presenting anti-ETAR/AT1R abs positivity, although the result was not statistically significant (OR 0.5, 95% CI 0.11-2.28).

Conclusions. Anti-ETAR/AT1R abs could be involved in peripheral vasculopathy in SSc patients, both in early and in late phases of the disease. Further studies are needed to evaluate their potential predictive value aimed at selection of patients at risk for early treatment or prevention therapy.