Glucose-6-phosphate isomerase variants play a key role in the generation of anti-GPI antibodies: possible mechanism of autoantibody production.
Glucose-6-phosphate isomerase (GPI), recognized as an autoantigen in the K/BxN arthritis model, is a ubiquitous cytoplasmic enzyme. Anti-GPI antibodies (Abs) are also detected in the serum of patients with arthritic diseases including rheumatoid arthritis (RA). So far, 24 GPI variants have been reported and most of these variants relate to non-spherocytic hemolytic disease. To understand the mechanisms of anti-GPI Ab production, cDNAs from peripheral blood mononuclear cells of subjects with or without anti-GPI Abs were cloned and sequenced. We identified 39 new GPI variants (57-1596 bp). The frequency of GPI variants in healthy control subjects (HS) with anti-GPI Abs (27/73, 31.5%) was significantly higher than that in anti-GPI Ab-negative HS (5/78, 6.4%, p < 0.001). The frequency of GPI variants in anti-GPI Ab-positive RA patients (22/77, 28.6%) was more significantly higher than in anti-GPI Ab-negative patients (1/63, 1.6%, p < 0.0001). Our results suggest that GPI variants may play a crucial role in the production of autoantibodies against ubiquitous GPI autoantigens.
Muraki
Yoshifumi
Y
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tenodai, Ibaraki 305-8575, Japan.
Matsumoto
Isao
I
Chino
Yusuke
Y
Hayashi
Taichi
T
Suzuki
Eiji
E
Goto
Daisuke
D
Ito
Satoshi
S
Murata
Hideyuki
H
Tsutsumi
Akito
A
Sumida
Takayuki
T
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000276:immunology*; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D001323:Autoantibodies; D007527:Isoenzymes; D005956:Glucose-6-Phosphate Isomerase