与IgM单克隆丙种球蛋白病相关的多发性神经病中的免疫球蛋白基因分析

Immunoglobulin gene analysis in polyneuropathy associated with IgM monoclonal gammopathy.

作者信息

Eurelings Marijke, Notermans Nicolette C, Lokhorst Henk M, van Kessel Berris, Jacobs Bart C, Wokke John H J, Sahota Surinder S, Bloem Andries C

机构信息

Department of Neurology, the Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

出版信息

J Neuroimmunol. 2006 Jun;175(1-2):152-9. doi: 10.1016/j.jneuroim.2006.02.008. Epub 2006 Mar 6.

DOI:10.1016/j.jneuroim.2006.02.008

PMID:16600385

Abstract

Antineural antibody activity is the implicated pathogenic mechanism in polyneuropathy associated with monoclonal gammopathy. Recognition of antigen depends on immunoglobulin variable regions, encoded by V genes. We studied V(H)DJ(H) and V(L)J(L) gene use in monoclonal B cells by clonal analysis in 20 patients with polyneuropathy and IgM monoclonal gammopathy. V genes associated with bacterial responses appear over-represented and V(H)3-23 was preferentially used, without association with specific D, J(H) or V(L)J(L). V genes revealed somatic mutation and intraclonal variation was found in 9 of 20 patients. Polyneuropathy associated with monoclonal gammopathy may be caused by an immune response to bacterial antigens, which recruit somatically mutated autoreactive B cells.

摘要

抗神经抗体活性是与单克隆丙种球蛋白病相关的多发性神经病的潜在致病机制。对抗原的识别取决于由V基因编码的免疫球蛋白可变区。我们通过克隆分析研究了20例多发性神经病和IgM单克隆丙种球蛋白病患者单克隆B细胞中V(H)DJ(H)和V(L)J(L)基因的使用情况。与细菌反应相关的V基因出现过度表达，且优先使用V(H)3-23，与特定的D、J(H)或V(L)J(L)无关。V基因显示出体细胞突变，20例患者中有9例发现克隆内变异。与单克隆丙种球蛋白病相关的多发性神经病可能由对细菌抗原的免疫反应引起，这种反应募集了体细胞突变的自身反应性B细胞。