in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.
GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author, of John Hopkins University, Baltimore, and her colleagues wrote in .
Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.
In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.
Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.
Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.
Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).
Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.
“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.
This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).
Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).
Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).
However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).
Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.
They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).
“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.
“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.
The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22.