Background/Purpose: Previous studies have shown that anticentromere (AC) and isolated nucleolar (NUC) antibodies are the most common autoantibodies in patients with systemic sclerosis (SSc) and World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH).  The goal of the present study was to determine the association between serum autoantibodies and survival in patients with newly diagnosed PAH who are enrolled in the PHAROS (Pulmonary Hypertension and Recognition of Outcomes in Scleroderma) Registry.

Methods: We evaluated patients from the multi-center, prospective, observational PHAROS registry who had definite PAH diagnosed by right-heart catheterization (RHC) (mean pulmonary artery pressure (mPAP) ³ 25mmHg and pulmonary capillary wedge pressure (PCWP) ² 15mmHg) within 6 months of enrollment. Medical history, laboratory (including serum autoantibodies), pulmonary function test, echocardiogram, 6-minute walk distance, and RHC data were collected at baseline and biannually or as clinically indicated. Mortality data were collected from participating centers’ electronic medical records and/or the Social Security Death Index. Kaplan-Meier estimates for survival were determined for 6 different autoantibody groups.  Multivariable Cox regression analyses were performed to assess risk of death by hazard ratios (HR) in each autoantibody group, controlling for age, sex, SSc disease duration (defined as duration since first Raynaud symptom), forced vital capacity (FVC) % predicted, and skin score.

Results: 163 PHAROS subjects met WHO group 1 PAH criteria and had serum autoantibody information available (7 missing autoantibody data, 7 with negative autoantibody test). More than half had either AC or NUC; 61 (36%) subjects had AC, 39 (23%) NUC, 11 (6%) Scl70, 28 (16%) had mixed/other, 9 (5%) RNA polymerase III (RNApol), 8 (5%) U1RNP autoantibodies. The mean SSc disease duration at PAH diagnosis was longest for AC (19.3±13.4y) and shorter for NUC patients (12.2±9.8, compared to AC p=0.02).  Thirty-two (21%) subjects died over a mean follow-up time of 2.4±1.7 (median 2.0, range 0-7.2) years. 1-, 3-year survival across all antibody groups was 93% and 77%; 1- and 3-year survival estimates were 94% and 72% for AC; 94% and 79% for NUC; 89% and 63% for Scl70; 100% and 86% for U1RNP; 92% and 79% for mixed/other. No patient with RNApol or negative autoantibodies died over the follow-up period.  For all autoantibody groups, unadjusted and adjusted HR revealed no statistically significant association between risk of death and autoantibody positivity.

Conclusion: Anticentromere and NUC autoantibodies are prevalent in SSc patients with PAH.  PAH may be a late complication in AC patients, but may occur earlier in SSc patients with other autoantibodies.  There does not appear to be a significant association between SSc antibody type and survival in patients with PAH.