Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders

Arthritis Rheum. 2003 Apr;48(4):944-54. doi: 10.1002/art.10898.


Objective: Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti-GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population-matched healthy control subjects.

Methods: Anti-GPI antibodies were assayed in 811 individual serum samples by enzyme-linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting.

Results: Several patients had significantly elevated anti-GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti-GPI antibodies (range 12-29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti-GPI antibodies at similar frequencies (12-25%). Similar titers were detected in a proportion (5-10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus.

Conclusion: No disease-specific pattern of antibody positivity to GPI was apparent. While the antibody-mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Arthritis, Psoriatic / immunology
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / immunology*
  • Autoantigens / immunology
  • Crohn Disease / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glucose-6-Phosphate Isomerase / immunology*
  • Humans
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Recombinant Proteins / immunology
  • Sarcoidosis / immunology
  • Spondylitis, Ankylosing / immunology


  • Autoantibodies
  • Autoantigens
  • Recombinant Proteins
  • Glucose-6-Phosphate Isomerase