Anti–RNPC-3 (U11/U12) Antibodies in Systemic Sclerosis in Patients With Moderate-to-Severe Gastrointestinal Dysmotility

Objective: To examine the association of anti–RNPC-3 antibodies in patients with systemic sclerosis (scleroderma or SSc) with selected gastrointestinal (GI) tract complications. Methods: Sera from patients with SSc with or without severe GI dysfunction (total parenteral nutrition dependence) from the Johns Hopkins Scleroderma Center were screened for anti–RNPC-3 antibodies. We then examined anti–RNPC-3–positive cases and negative SSc controls from the University of Pittsburgh and the University of Pittsburgh Medical Center (UPMC) scleroderma cohort to confirm our findings and to examine whether specific GI features were associated with anti–RNPC-3 antibodies. Results: In the discovery cohort, patients with SSc with severe GI dysfunction (n = 37) and without GI dysfunction (n = 38) were screened for anti–RNPC-3 antibodies. The former were more likely to have anti–RNPC-3 antibodies (14% versus 3%; P = 0.11). In the Pittsburgh cohort, moderate-to-severe GI dysfunction (Medsger GI score ≥2) was present in 36% of anti–RNPC-3–positive patients versus 15% of anti–RNPC-3–negative patients (P ≤ 0.01). Anti–RNPC-3–positive patients were more likely to be male (31% versus 15%; P = 0.04), African American (18% versus 6%; P = 0.02), have esophageal dysmotility (93% versus 62%; P < 0.01), and interstitial lung disease (ILD) (77% versus 35%; P < 0.01). After adjusting for relevant covariates and potential confounders, moderate-to-severe GI disease was associated with anti–RNPC-3 antibodies (odds ratio [OR] 3.8 [95% confidence interval (95% CI) 1.0–14.3]), and ILD trended toward significance (OR 2.8 [95% CI 1.0–8.2]). Conclusion: Patients with SSc and anti–RNPC-3 antibodies are more likely to be male and African American and to have moderate-to-severe GI disease and ILD. Further studies on larger patient cohorts may be helpful in further defining subsets of patients with SSc at risk for severe GI involvement.