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Analysis of immunoglobulin variable region genes of a human IgM anti-myeloperoxidase antibody derived from a patient with vasculitis.

机译:来源于血管炎患者的人IgM抗髓过氧化物酶抗体的免疫球蛋白可变区基因分析。

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摘要

Circulating antibodies to myeloperoxidase (MPO) are associated primarily with pauci-immune glomerulonephritis and systemic vasculitis. Anti-MPO antibodies belong to a group of autoantibodies, anti-neutrophil cytoplasmic antibodies, that may play a pathogenic role in vasculitis. We have generated a human monoclonal anti-MPO antibody (E3-MPO) using peripheral blood lymphocytes from a patient with microscopic polyarteritis. Variable region gene analysis of E3-MPO showed that the VH region had 90% homology with the germ line gene VH4-21. E3-MPO was also shown to carry the 9G4 idiotope, which so far has been associated only with human antibodies that utilize the VH4-21 gene. The 9G4 idiotope was also expressed on anti-MPO antibodies in sera from the donor patient and from 4/7 additional patients with active, untreated vasculitis. The nucleotide sequences of both the variable heavy and light chains of E3-MPO showed evidence of an antigen-driven response.
机译:髓过氧化物酶(MPO)的循环抗体主要与免疫球蛋白免疫性肾小球肾炎和全身性血管炎有关。抗MPO抗体属于一组自身抗体,即抗中性粒细胞胞质抗体,可能在血管炎中发挥致病作用。我们已经使用来自患有显微多动脉炎的患者的外周血淋巴细胞产生了人单克隆抗MPO抗体(E3-MPO)。 E3-MPO的可变区基因分析表明,VH区与种系基因VH4-21具有90%的同源性。 E3-MPO还被证明带有9G4独特型,迄今为止,它仅与利用VH4-21基因的人抗体相关。 9G4独特型也在供体患者和其他患有活动性,未经治疗的血管炎的患者中的4/7患者的血清抗MPO抗体上表达。 E3-MPO的可变重链和轻链的核苷酸序列均显示出抗原驱动反应的证据。

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