著者

Iwanami Keiichi Matsumoto Isao Tanaka Yoko Inoue Asuka Goto Daisuke Ito Satoshi Tsutsumi Akito Sumida Takayuki

出版者

BioMed Central

雑誌

Arthritis research & therapy (ISSN:14786354)

巻号頁・発行日

vol.10, no.6, pp.R130, 2008-11

被引用文献数

31 21

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IntroductionArthritis induced by immunisation with glucose-6-phosphate isomerase (GPI) in DBA/1 mice was proven to be T helper (Th) 17 dependent. We undertook this study to identify GPI-specific T cell epitopes in DBA/1 mice (H-2q) and investigate the mechanisms of arthritis generation.MethodsFor epitope mapping, the binding motif of the major histocompatibility complex (MHC) class II (I-Aq) from DBA/1 mice was identified from the amino acid sequence of T cell epitopes and candidate peptides of T cell epitopes in GPI-induced arthritis were synthesised. Human GPI-primed CD4+ T cells and antigen-presenting cells (APCs) were co-cultured with each synthetic peptide and the cytokine production was measured by ELISA to identify the major epitopes. Synthetic peptides were immunised in DBA/1 mice to investigate whether arthritis could be induced by peptides. After immunisation with the major epitope, anti-interleukin (IL) 17 monoclonal antibody (mAb) was injected to monitor arthritis score. To investigate the mechanisms of arthritis induced by a major epitope, cross-reactivity to mouse GPI peptide was analysed by flow cytometry and anti-GPI antibodies were measured by ELISA. Deposition of anti-GPI antibodies on the cartilage surface was detected by immunohistology.ResultsWe selected 32 types of peptides as core sequences from the human GPI 558 amino acid sequence, which binds the binding motif, and synthesised 25 kinds of 20-mer peptides for screening, each containing the core sequence at its centre. By epitope mapping, human GPI325–339 was found to induce interferon (IFN) γ and IL-17 production most prominently. Immunisation with human GPI325–339 could induce polyarthritis similar to arthritis induced by human GPI protein, and administration of anti-IL-17 mAb significantly ameliorated arthritis (p < 0.01). Th17 cells primed with human GPI325–339 cross-reacted with mouse GPI325–339, and led B cells to produce anti-mouse GPI antibodies, which were deposited on cartilage surface.ConclusionsHuman GPI325–339 was identified as a major epitope in GPI-induced arthritis, and proved to have the potential to induce polyarthritis. Understanding the pathological mechanism of arthritis induced by an immune reaction to a single short peptide could help elucidate the pathogenic mechanisms of autoimmune arthritis.

著者

伊藤 聡 Ito Satoshi

出版者

筑波大学

雑誌

筑波フォーラム (ISSN:03851850)

巻号頁・発行日

no.71, pp.3-6, 2005-11

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人は突然遭遇した驚愕する状況では普段では想像できない反応を示したり、あるいは普段ならすぐに対処できるはずのことに対処できなくなったりするようである。私は2年前に筑波大に赴任したが、前任地の新潟での忘れられない事件3件を ...

著者

Kawasaki Aya Ito Ikue Ito Satoshi Hayashi Taichi Goto Daisuke Matsumoto Isao Takasaki Yoshinari Hashimoto Hiroshi Sumida Takayuki Tsuchiya Naoyuki

出版者

Hindawi Publishing

雑誌

Journal of biomedicine and biotechnology (ISSN:11107243)

巻号頁・発行日

vol.2010, pp.207578, 2010

被引用文献数

27 15

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Recent genome-wide association studies demonstrated association of single nucleotide polymorphisms (SNPs) in the TNFAIP3 region at 6q23 with systemic lupus erythematosus (SLE) in European-American populations. In this study, we investigated whether SNPs in the TNFAIP3 region are associated with SLE also in a Japanese population. A case-control association study was performed on the SNPs rs13192841, rs2230926, and rs6922466 in 318 Japanese SLE patients and 444 healthy controls. Association of rs2230926 G allele with SLE was replicated in Japanese (allelic association P=.033, odds ratio [OR] 1.47, recessive model P=.023, OR 8.52). The association was preferentially observed in the SLE patients with nephritis. When the TNFAIP3 mRNA levels of the HapMap samples were examined using GENEVAR database, the presence of TNFAIP3 rs2230926 G allele was associated with lower mRNA expression of TNFAIP3 (P=.013). These results indicated that TNFAIP3 is a susceptibility gene to SLE both in the Caucasian and Asian populations.