Background/Purpose: Rheumatoid arthritis (RA) is a complex autoimmune disease with genetic and environmental contributions. There has been increasing interest in the microbiome and its potential contribution to the pathogenesis of the inflammatory arthritides. Our recent study suggest that RA patients have altered intestinal microbiota compared to healthy controls. Here we aimed to investigate the local immunologic response in the intestinal tract of RA patients, including humoral signatures and pro-inflammatory cytokine profile. Mucosal response against enteric bacteria may offer insights into the pathogenesis of RA and the potential identification of subsets of patients amenable to therapeutic interventions.

Methods: RA status, clinical activity and sociodemographic factors were determined in patients with New-onset RA (NORA; n=15), Chronic-established RA (CRA; n=14), and matched healthy subjects (n=14). Fecal samples were obtained and total protein was extracted. ELISA assays were performed to determine concentrations of secretory (s) IgA, anti-cyclic citrullinated peptides antibodies (anti-CCP3.1), and various pro-inflammatory cytokines by multiplex assay.

Results: RA patients show aberrant intestinal humoral responses manifested by elevated fecal sIgA levels. Elevated levels of anti-CCP antibodies were found in fecal samples of these patients (mean= 64.9 Units vs 14.7 Units in healthy controls; P=0.03), suggesting that the intestinal tract is a potential site for peptide citrullination. Intriguingly, the gut anti-CCP3.1 levels in CRA patients were higher compared to NORA (p=0.10).  NORA patients have significantly elevated fecal IL-1β compared to controls (mean= 4.2 pg/ml vs 1.67, p=0.02) as well as other pro-inflammatory cytokines including TNFa. These changes are associated with an intestinal microbiota alteration in NORA patients, characterized by a higher prevalence of Prevotella spp.

Conclusion: Our results show evidence of an amplified adaptive immune response and subclinical inflammation within the intestinal tract of patients with RA. To our knowledge, detection of the aforementioned fecal immunoglobulins and cytokines in RA patients has not been previously described. These findings suggest that immunologic defense mechanisms against intestinal bacteria may play a role in the pathogenesis of RA and that the intestinal tract is a potential site of peptide citrullination. Further studies are warranted to validate our findings.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-fecal-secretory-immunoglobulin-a-anti-cyclic-citrullinated-peptide-antibodies-and-cytokine-levels-in-rheumatoid-arthritis-patients/