Association of Antibodies to Prevotella copri in Anti-Cyclic Citrullinated Peptide-Positive Individuals At Risk of Developing Rheumatoid Arthritis and in Patients With Early or Established Rheumatoid Arthritis

Arthritis Rheumatol. 2023 Apr;75(4):507-516. doi: 10.1002/art.42370. Epub 2023 Feb 22.

Abstract

Objective: Prevotella copri (P copri), a gut commensal, has been reported to be an immune-relevant organism in individuals with rheumatoid arthritis (RA). This study sought to evaluate anti-P copri (anti-Pc) antibody responses in our participant cohorts and to determine when in the natural history of RA such responses develop.

Methods: We analyzed serum levels of immunoglobulin A (IgA) and IgG antibodies from a 27-kd protein of P copri (anti-Pc-p27), an immunogenic P copri protein, in study participants at risk of developing RA, participants who transitioned to RA, participants with early RA (<1 year of disease), and participants with established RA, with comparisons made to their matched controls. We also evaluated anti-Pc-p27 antibody levels in individuals stratified by RA-related autoantibody status.

Results: Overall, participants with RA had significantly higher IgA anti-Pc-p27 antibody levels and trended toward higher IgG anti-Pc-p27 antibody levels compared with matched controls. When stratified by early versus established RA, participants with early RA had median IgG anti-Pc-p27 antibody levels that were overall higher, whereas median IgA anti-Pc-p27 antibody levels were statistically significantly higher in participants with established RA compared with their matched controls. In the autoantibody-specific analyses, the at-risk population with anti-cyclic citrullinated peptide (anti-CCP) antibodies, but not rheumatoid factor (RF), trended toward increased levels of IgG anti-Pc-p27. Additionally, RA participants who were seropositive for both CCP and RF had significantly increased levels of IgA anti-Pc-p27 antibodies and trended toward higher levels of IgG anti-Pc-p27 antibodies compared with matched controls.

Conclusion: Our findings support a potential etiologic role for P copri in both RA preclinical evolution and the subsequent pathogenesis of synovitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Citrullinated Protein Antibodies
  • Arthritis, Rheumatoid*
  • Autoantibodies
  • Humans
  • Immunoglobulin A
  • Immunoglobulin G
  • Peptides, Cyclic
  • Rheumatoid Factor

Substances

  • Autoantibodies
  • Rheumatoid Factor
  • Peptides, Cyclic
  • Anti-Citrullinated Protein Antibodies
  • Immunoglobulin G
  • Immunoglobulin A

Supplementary concepts

  • Prevotella copri