Clonal immunoglobulin λ light-chain gene rearrangements detected by next generation sequencing in POEMS syndrome
Clonal immunoglobulin λ light-chain gene rearrangements detected by next generation sequencing in POEMS syndrome
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DOI：
10.1002/ajh.25213
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发表时间：
2018-09-01
影响因子：
12.8
通讯作者：
Nakaseko, Chiaki
中科院分区：
文献类型：
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作者：
Kawajiri-Manako, Chika;Minnura, Naoya;Nakaseko, Chiaki
多发性神经病、脏器肥大、内分泌疾病、M蛋白和皮肤变化(POEMS)综合征是一种罕见的浆细胞异位症，以多发性神经病变、器官肥大、内分泌疾病、血管外液体超载、M蛋白和多种皮肤变化为特征。发病机制尚不清楚，但单克隆性浆细胞和这些免疫球蛋白是有限的。轻链可变区(IGLV)基因仅来自两个生殖系，IGLV1-44或1-40。为了了解POEMS综合征(n=30)患者IGLV基因的克隆组成，我们采用下一代测序技术(NGS)分析了骨髓单个核细胞基因组DNA中IGLV基因的克隆性重排。11例POEMS患者的POEMS综合征特异性胚系序列的显性IGLV基因重排显著增加(36.7%；IGLV1-44：n=9，IGLV1-40：n=2)。在某些情况下，通过异源双链(HD)分析和Sanger测序，未检测到IGLV基因重排克隆的显著增加，而是通过异源双链(HD)分析和Sanger测序检测到了IGLV基因重排克隆，这表明相当少量的单克隆浆细胞可能产生了大量的单抗蛋白的mRNA。然而，显性无性系大小的显著增加与初始病情没有直接联系。另一方面，在显性克隆显著增加的病例中，随着疾病的缓解和复发，它们减少和增加。这些数据表明，单克隆性浆细胞与POEMS综合征的发病机制有关。
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, extravascular fluid overload, M protein, and a myriad of skin changes. The pathogenesis is poorly understood, but monoclonal plasma cells are.-restricted and these immunoglobulin. light chain variable (IGLV) region genes are derived from only two germlines, either IGLV1-44 or 1-40. Here we analyzed the clonal IGLV gene rearrangements of genomic DNA samples of bone marrow mononuclear cells using next-generation sequencing (NGS) to understand the clonal composition of IGLV genes in patients with POEMS syndrome (n = 30). The dominant IGLV gene rearrangement of POEMS syndrome-specific germline sequences were significantly increased in 11 POEMS patients (36.7%; IGLV1-44: n = 9, IGLV1-40: n = 2). In some cases, IGLV gene rearrangement clone was not detected as significant increase but was detected using cDNA samples by heteroduplex (HD) analysis and Sanger sequencing, suggesting that the quite small number of monoclonal plasma cells may produce large quantity of mRNA of monoclonal proteins. However, significant increase of dominant clone sizes was not directly linked to the initial disease status. On the other hand, in cases with significantly increased dominant clones, they decreased and increased accompanying with disease remission and relapse. These data demonstrate that monoclonal plasma cells are related to the pathogenesis of POEMS syndrome.