title: Biased usage of synovial immunoglobulin heavy chain variable region 4 by the anti-glucose-6-phosphate isomerase antibody in patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is the most common inflammatory arthritis, characterized by marked infiltration of mononuclear cells including B cells into the inflamed synovium. Anti-glucose-6-phosphate isomerase (GPI) antibody (Ab) is an arthritogenic Ab in K/BxN T cell receptor transgenic mice, and is also present in some patients with RA. To characterize synovial B cells from anti-GPI Ab-positive RA, synovial immunoglobulin (Ig) heavy chain variable regions (VH) were compared with those of negative individuals. Synovial tissues were obtained from six RA patients (three anti-GPI Ab-positive and three anti-GPI Ab-negative). Ig-VH genes were amplified by PCR using family-specific primers and were subsequently sequenced. In synovial B cells from anti-GPI Ab-positive RA patients, VH4 and JH4 were predominantly expressed (p<0.0001). The immunoglobulin heavy chain complementarity-determining region 3 (IgH-CDR3) length in the synovium of anti-GPI Ab-positive individuals was shorter than that in anti-GPI Ab-negative individuals (p=0.0005). In addition, the IgH-CDR3 of anti-GPI Ab-positive patients was rich in basic-ionized amino acids (arginine, histidine, and lysine) near their central position, suggesting a high affinity. Our results support the notion that Ig-VH4 B cells in RA synovium with anti-GPI Ab are affinity-matured and that anti-GPI Ab might be associated with the skewed IgH-CDR3.
authors.affiliation: Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Takanori
authors.initials: T
authors.lastname: Yasukochi
authors.forename: Mizuko
authors.initials: M
authors.lastname: Mamura
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: Takayuki
authors.initials: T
authors.lastname: Sumida
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D050438:Genes, Immunoglobulin Heavy Chain; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D013582:Synovial Fluid / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D005956:Glucose-6-Phosphate Isomerase