Immunoglobulin G from anti-glucose-6-phosphate isomerase antibodies positive patient with rheumatoid arthritis induces synovitis in cynomolgus monkeys.
Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) solely induce arthritis in mice. High titers of anti-GPI Abs are found in some patients with rheumatoid arthritis (RA), but their pathogenic role remains elusive. The aim of this study was to evaluate the pathogenic role of anti-GPI Abs in cynomolgus monkeys. IgG fractions were separated from sera of anti-GPI Abs-positive RA patients and healthy subjects and directly injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. At day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from monkey joints. In monkey joints, IgG including anti-GPI Abs resulted in recruitment of granulocytes and mononuclear cells, strong deposition of human IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients including anti-GPI Abs may play a crucial role in the generation of synovitis in monkeys, although the pathogenesis of anti-GPI Abs in RA patients is still uncertain.
Suzuki
Takeshi
T
Clinical Immunology, Major of Advanced Biomedical Applications, Graduate of Comprehensive Human Sciences, University of Tsukuba, University of Tsukuba, 1-1-1 Tenodai, Ibaraki 305-8575, Japan.
Muraki
Yoshifumi
Y
Yasukochi
Takanori
T
Zhang
Hua
H
Kori
Yuko
Y
Wakamatsu
Ei
E
Hayashi
Taichi
T
Goto
Daisuke
D
Ito
Satoshi
S
Tsutsumi
Akito
A
Sumichika
Hiroshi
H
Sumida
Takayuki
T
Matsumoto
Isao
I
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology*; D001323:Autoantibodies / Q000008:administration & dosage* / Q000378:metabolism; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000378:metabolism; D008252:Macaca fascicularis; D044087:Receptor, Anaphylatoxin C5a / Q000096:biosynthesis / Q000235:genetics; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D013585:Synovitis / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D044087:Receptor, Anaphylatoxin C5a; D005956:Glucose-6-Phosphate Isomerase