Objective Prevotella copri, an intestinal microbe, may over-expand in stool samples of patients with new-onset rheumatoid arthritis (NORA), but it is not yet clear whether the organism has immune relevance in RA pathogenesis. Methods HLA-DR-presented peptides (T cell epitopes) from P. copri were sought directly from patients' synovial tissue or peripheral blood mononuclear cells (PBMC) using tandem mass spectrometry, followed by testing the antigenicity of peptides or their source proteins using samples from RA patients or comparison groups. T cell reactivity was determined by ELISpot assays; antibody responses were measured by ELISA, and cytokine/chemokine determinations were made by Luminex. 16S rDNA of P. copri was sought in serum and synovial fluid samples using nested PCR. Results In PBMC, we identified an HLA-DR-presented peptide from a 27-kD protein of P. copri (Pc-p27), which stimulated Th1 responses in 42% of NORA patients. In both NORA and chronic RA patients, one subgroup had IgA antibody responses to Pc-p27 or the whole organism, which correlated with Th17 cytokine responses and frequent anti-citrullinated protein antibodies (ACPA). The other subgroup had IgG P. copri antibodies, which were associated with Prevotella DNA in synovial fluid, P. copri-specific Th1 responses, and less frequent ACPA. In contrast, P. copri antibody responses were rarely found in patients with other rheumatic diseases or in healthy controls. Conclusion Subgroups of RA patients have differential IgG or IgA immune reactivity with P. copri, which appears to be specific for this disease. These observations provide evidence that P. copri is immune-relevant in RA pathogenesis.

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To discover novel autoantigens associated with Lyme arthritis (LA), we identified T-cell epitopes presented in vivo by human leukocyte antigen (HLA)-DR molecules in patients' inflamed synovial tissue or joint fluid and tested each epitope for autoreactivity. Using this approach, we identified the highly expressed human protein, apolipoprotein B-100 (apoB-100), as a target of T- and B-cell responses in a subgroup of LA patients. Additionally, the joint fluid of these patients had markedly elevated levels of apoB-100 protein, which may contribute to its autoantigenicity. In patients with antibiotic-refractory LA, the magnitude of apoB-100 antibody responses correlated with increased numbers of plasma cells in synovial tissue, greater numbers and activation of endothelial cells, and more synovial fibroblast proliferation. Thus, a subset of LA patients have high levels of apoB-100 in their joints and autoreactive T- and B-cell responses to the protein, which likely contributes to pathogenic autoimmunity in patients with antibiotic-refractory LA.