Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from patients with inflammatory arthritis.
BACKGROUND
In K/BxN mice, anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are arthritogenic, and their transfer into naive mice induces arthritis. Anti-GPI Abs develop in many human patients with RA and are associated with more severe forms of the disease.


OBJECTIVE
To elucidate the serum and synovial fluid (SF) anti-GPI IgG profiles among different patient groups with a variety of arthritides.


METHODS
Blood and SF obtained concomitantly from 91 patients with clinically well defined arthritis were tested for concentrations of total anti-GPI IgG, anti-GPI IgG subclasses, B lymphocyte stimulator (BLyS), and APRIL by ELISA.


RESULTS
Anti-GPI IgG was detected in sera and SF of patients with many arthritic diseases, but was preferentially associated with inflammatory arthritis, in general, and RA, in particular. The anti-GPI IgG subclass usage was skewed and varied among the different arthritic disease groups. Inverse correlations between serum levels of BLyS and anti-GPI IgG and positive correlations between serum levels of APRIL and anti-GPI IgG were seen among immune based arthritic patients and patients with RA but not among non-immune based patients. No correlations were found in SF from any group of arthritic patients.


CONCLUSIONS
Raised circulating anti-GPI Abs are not unique to patients with RA but are present in many patients with inflammatory arthritis. The difference in anti-GPI IgG subclass usage among disease groups may influence effector function and disease outcome. The inverse correlation between serum BLyS and anti-GPI IgG levels suggests that anti-GPI B cells may be regulated differently from other autoantibody producing B cells. Anti-GPI Abs may serve a pathogenic function in humans by promoting the maintenance of existing disease.
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
M
M
Schaller
W
W
Stohl
S M
SM
Tan
V M
VM
Benoit
D M
DM
Hilbert
H J
HJ
Ditzel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001168:Arthritis / Q000276:immunology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D053264:B-Cell Activating Factor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis* / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000097:blood; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000097:blood; D013582:Synovial Fluid / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C490341:ANP32B protein, human; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D008565:Membrane Proteins; D009687:Nuclear Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D005956:Glucose-6-Phosphate Isomerase