Identification of Novel, Immunogenic HLA-DR-Presented Prevotella copri Peptides in Patients With Rheumatoid Arthritis

Objective We previously identified HLA-DR-presented epitopes from a 27-kd protein of Prevotella copri (Pc) obtained from peripheral blood mononuclear cells (PBMCs) from 1 rheumatoid arthritis (RA) patient. Herein, we sought to identify other HLA-DR-presented Pc peptides and source proteins in PBMCs from additional patients to better understand Pc immune responses and RA disease pathogenesis. Methods Using tandem mass spectrometry, we searched for HLA-DR-presented Pc peptides in PBMCs from RA and Lyme arthritis (LA) patients. The identified peptides and source proteins were tested for reactivity in RA patients, those with other arthritides, and the general population. These results were assessed for correlation with clinical findings. Results Including Pc-p27, we identified 5 HLA-DR-presented Pc peptides, each derived from a different Pc protein, in 3 of 4 RA patients, but none in 2 LA patients. When tested in our RA cohort, 14 of 19 patients (74%) had T cell responses, and 47 of 89 patients (53%) had IgG or IgA responses to >= 1 of the 5 Pc peptides or proteins, most commonly IgA reactivity with Pc-p27. Additionally, 74% of RA patients with IgA antibodies to >= 1 Pc protein had anti-citrullinated protein antibodies (ACPAs) compared with 49% of patients who lacked IgA Pc antibody responses (P = 0.05), and IgA Pc antibody levels correlated with ACPA values. Conclusion The majority of the RA patients had Pc immune responses. The correlation of IgA Pc antibody responses, particularly to Pc-p27, with ACPA supports the hypothesis that specific microbial antigens in the mucosa have a role in shaping or amplifying immune responses in RA joints.

Automated summary

Using tandem mass spectrometry, this study identified 5 HLA-DR-presented Pc peptides, each derived from a different Pc protein, in PBMCs from RA patients. Among the RA patients, 74% had T cell responses, and 53% had IgG or IgA responses to at least one of the 5 Pc peptides or proteins, with IgA reactivity with Pc-p27 being the most common. Furthermore, a correlation was found between IgA Pc antibody responses and ACPA levels in RA patients, suggesting a role of specific microbial antigens in shaping immune responses in RA joints.