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


CONCLUSIONS
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.
Matsumoto
Isao
I
Joslin Diabetes Center and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Lee
David M
DM
Goldbach-Mansky
Raphaela
R
Sumida
Takayuki
T
Hitchon
Carol A
CA
Schur
Peter H
PH
Anderson
Ronald J
RJ
Coblyn
Jonathan S
JS
Weinblatt
Michael E
ME
Brenner
Michael
M
Duclos
Bernard
B
Pasquali
Jean-Louis
JL
El-Gabalawy
Hani
H
Mathis
Diane
D
Benoist
Christophe
C
D000328:Adult; D015535:Arthritis, Psoriatic / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D012507:Sarcoidosis / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D011994:Recombinant Proteins; D005956:Glucose-6-Phosphate Isomerase