PO:33:194 | The role of anti-g protein-coupled receptors antibodies in the assessment of systemic sclerosis-primary heart involvement

Beatrice Moccaldi¹, Giovanni Civieri², Annagrazia Cecere², Marco Binda¹, Marta Vadori², Laura Iop², Marta Tonello¹, Anna Cuberli¹, Andrea Benini¹, Emanuele Cozzi², Andrea Doria¹, Francesco Tona², Elisabetta Zanatta^1|2. | ¹Unità di Reumatologia, Dipartimento di Medicina ^DIMED, Università di Padova, Padova, Italy; ²Dipartimento di Scienze Cardio-Toraco-Vascolari e Sanità Pubblica, Università di Padova, Padova, Italy.

Background. Primary heart involvement (pHI) is a major organ complication of systemic sclerosis (SSc), accounting for a significant share of SSc-related deaths. Since pHI is often asymptomatic and its presentation is highly variable, a multiparametric assessment is mandatory. Echocardiography is essential in pHI screening; coronary flow velocity reserve (CFR) assessed by echocardiography has been demonstrated to identify SSc patients with coronary microvascular dysfunction (CMD), which appears to be involved in the pathogenesis of SSc-pHI. Autoantibodies targeting G protein-coupled receptors (GPCRs) – specifically, anti-endothelin type A and anti-angiotensin 1 receptors antibodies (anti-ETAR and anti-AT1R) – have been associated with the microvascular manifestations of SSc, namely digital ulcers and pulmonary arterial hypertension. Our study aims to evaluate a possible association between anti-GPCRs antibodies and CMD in SSc patients.

Materials and Methods. Adult patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were enrolled; patients with pulmonary arterial hypertension, coronary artery disease or other cardiomyopathies were excluded. Demographic and clinical data were recorded, as well as the presence of pHI(1). Echocardiography with CFR assessment was performed on all patients by an experienced cardiologist: according to the literature, CFR < 2.5 was considered marker of CMD, while CFR values < 2 defined severe CMD. Serum levels of anti-ETAR and anti-AT1R antibodies were assessed by ELISA for each patient up to 3 months prior or following the echocardiographic assessment. The seropositive threshold was provided by the manufacturer (>10 U/ml).

Results. Thirty-one patients were enrolled. The median disease duration was 1 year (IQR 1-4), the median age at enrolment was 58 (48-63) years, the majority of patients were females (71%), had diffuse cutaneous SSc (61%) and positive anti-topoisomerase I antibodies (55%). Clinically overt pHI was diagnosed in 26% patients, while CMD in 70%. CMD was not associated with organ involvement, including pHI, while CFR values < 2 were associated with pHI. Serum anti-ETAR and anti-AT1R levels strongly correlated with each other (p<0.001). Positive anti-ETAR and anti-AT1R were associated with significantly lower CFR values (p=0.002 and p=0.05), and both anti-ETAR and anti-AT1R titers inversely correlated with CFR values (rho =-0.41, p=0.03 and rho=-0.37, p=0.05, respectively). ROC curve analysis showed an acceptable performance of both anti-GPCRs in identifying CMD, with an area under the curve (AUC) of 0.74 for anti-ETAR and 0.72 for anti-AT1R antibodies. A positive correlation was observed between time from Raynaud’s phenomenon and anti-GPCRs titers (rho =0.36, p=0.04 and rho=0.38, p=0.02), while there was only a tendency for a correlation between anti-GPCRs titers and disease duration.

Conclusions. Anti-ETAR and anti-AT1R antibodies appear to be associated with the development of CMD is SSc and their determination may be useful in the early assessment of SSc-pHI.