title: The exploration of joint-specific immunoreactions on immunoglobulins G of anti-glucose-6-phosphate isomerase antibody-positive patients with rheumatoid arthritis.
abstract: The pathogenic role of autoantibodies in rheumatoid arthritis (RA) remains elusive. Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are candidates for arthritogenic Abs because they directly induce arthritis in mice. High titers of anti-GPI Abs are found in some RA patients with severe forms. The aim of this study was to analyze the role of IgG, including anti-GPI Abs, in the joints of RA patients. Synovial tissue was obtained from 6 patients with RA (3 anti-GPI Abs- positive and 3 anti-GPI Abs- negative) and compared histologically and immunohistochemically for IgG and C3 deposition. IgG fractions were separated from the sera of anti-GPI Abs-positive RA patients and healthy subjects, and injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. On day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of the C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from the monkeys' joints. The synovia of anti-GPI Abs-positive RA patients showed diffuse infiltration of cells, including mast cells, and strong deposition of IgG and C3. In monkeys, IgG from RA patients, including anti-GPI Abs, resulted in recruitment of granulocytes and mononuclear cells, strong deposition of 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 that of anti-GPI Abs, may play a role in the synovitis of RA, although the pathogenesis of human anti-GPI Abs is still uncertain.
authors.affiliation: Division of Rheumatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan. ismatsu@md.tsukuba.ac.jp
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Muraki
authors.forename: Takanori
authors.initials: T
authors.lastname: Yasukochi
authors.forename: Zhang
authors.initials: Z
authors.lastname: Hua
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kori
authors.forename: Taichi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Goto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Akito
authors.initials: A
authors.lastname: Tsutsumi
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sumichika
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000633:toxicity*; D001483:Base Sequence; D003176:Complement C3 / Q000032:analysis / Q000276:immunology; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D006098:Granulocytes / Q000276:immunology; D000882:Haplorhini; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000633:toxicity*; D007596:Joints / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology
chemical_list: D001323:Autoantibodies; C488033:C5AR1 protein, human; D003176:Complement C3; D007074:Immunoglobulin G; D008565:Membrane Proteins; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D005956:Glucose-6-Phosphate Isomerase