PDF(Pubmed)
Abstract：
Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.
摘要：
多发性骨髓瘤（MM）仍然是一种无法治愈的浆细胞恶性肿瘤。虽然它的起源是神秘的，已提示与包括丙型肝炎病毒(HCV)在内的感染性病原体有关.在这里，我们报告了9例具有未知意义的单克隆丙种球蛋白病（MGUS）或先前HCV感染的MM患者，其中6人接受抗病毒治疗。我们研究了丙种球蛋白病的演变过程,根据纯化的单克隆免疫球蛋白的抗-HCV治疗和抗原特异性，使用INNO-LIA™HCV评分测定法确定，斑点印迹分析,和多重感染性抗原微阵列。来自6/9患者的单克隆免疫球蛋白对HCV有反应。这些患者中有4人接受了抗病毒治疗，并且比未经治疗的患者有更好的进化。抗病毒治疗后，1例第三次复发的MM患者获得了完全缓解,且具有微小残留病阴性.对于两名没有接受抗病毒治疗的患者，疾病进展。对于两名单克隆免疫球蛋白对HCV无反应的患者，抗病毒治疗对MGUS或MM疾病无效.我们的结果表明HCV感染与MGUS和MM进展之间存在因果关系。当HCV被消除时，慢性抗原刺激消失，允许克隆浆细胞的控制。这为MGUS和骨髓瘤的治疗开辟了新的可能性。
