Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens
Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens
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DOI：
10.1172/jci.insight.95367
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发表时间：
2017-10-05
期刊：
影响因子：
8
通讯作者：
Hermouet, Sylvie
中科院分区：
文献类型：
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作者：
Bosseboeuf, Adrien;Feron, Delphine;Hermouet, Sylvie
成熟B细胞肿瘤的亚群与细胞内病原体如EB病毒（EBV）、丙型肝炎病毒（HCV）或幽门螺杆菌感染有关。然而，感染和免疫球蛋白分泌（Ig分泌）B增殖性疾病之间的关联在很大程度上仍未得到解决。我们研究了诊断为意义不明的单克隆丙种球蛋白病（MGUS）或多发性骨髓瘤（MM）的患者产生的单克隆IgG（mc IgG）是否针对感染性病原体。使用多重感染性抗原阵列（MIAA）测定来自大型患者队列（n = 244）的纯化mc IgG的抗原特异性，该阵列筛选与9种病原体的纯化抗原或裂解物的反应性。23.4%的患者（57/244）的纯化mc IgG特异性识别MIAA中的1种病原体。EBV是最常见的靶点（15.6%），38个mc IgG中有36个识别EBV核抗原-1（EBNA-1）。与其他郁积型骨髓瘤/MM患者相比，EBNA-1特异性mc IgG（14.0%）MM患者的骨髓浆细胞浸润显著更大，β 2-微球蛋白和炎症/感染相关细胞因子水平更高。mcIgG检测的其他5种病原体为单纯疱疹病毒1型（2.9%）、水痘带状疱疹病毒（1.6%）、巨细胞病毒（0.8%）、丙型肝炎病毒（1.2%）和H. pylori（1.2%）。我们的结论是，对感染的免疫反应失调可能是患者亚群MGUS和MM疾病发作和/或进展的基础。
Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1-specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher beta(2)-microglobulin and inflammation/infection-linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients.