Clinical Pathology Laboratory, Ospedale Madre Giuseppina Vannini, Rome, Italy.
Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):6057-6062. doi: 10.26355/eurrev_201809_15943.
Mixed Cryoglobulinemia is the most well-known Hepatitis C Virus (HCV)-associated extrahepatic manifestation. MC is both an autoimmune and B-lymphoproliferative disorder. Cryoglobulins (CGs) are classified into three groups according to immunoglobulin (Ig) composition: type I is composed of one isotype or Ig class. Type II and type III mixed CGs are immune complexes composed of polyclonal IgGs acting as autoantigens and mono, polyclonal or oligoclonal IgM with rheumatoid factor activity. IgG1 and IgG3 are the predominant subclasses involved. This study shows the simultaneous presence of IgG-RF and IgG3, supporting the hypothesis of an involvement of this subclass in the initiation of early stages of CGs.
We describe a case series of six HCV-positive patients, all of whom had peripheral neuropathy and transient ischemic attacks, presenting cryoprecipitates formed by IgG3 and IgG1. Cryoprecipitate IgG subclass research was carried out by immunofixation electrophoresis by using antisera against IgG1, IgG2, IgG3, and IgG4.
Our six patients presented with an immunochemical pattern characterized by the mere presence of IgG1 and IgG3 subclasses with probable RF activity and one of these six patients exhibited monoclonal IgG3 in his cerebrospinal fluid.
We can hypothesize that the IgG passage through the blood-brain barrier could have contributed to the cause of TIAs, through a mechanism involving the precipitation of circulating immune complexes formed by the two subclasses in the intrathecal vessels.
混合性冷球蛋白血症是丙型肝炎病毒(HCV)相关性肝外表现中最常见的一种。MC 既是一种自身免疫性疾病,也是一种 B 细胞增殖性疾病。冷球蛋白根据免疫球蛋白(Ig)组成可分为三类:I 型由一种同种型或 Ig 类组成。II 型和 III 型混合冷球蛋白是由多克隆 IgG 作为自身抗原和具有类风湿因子活性的单克隆、多克隆或寡克隆 IgM 组成的免疫复合物。IgG1 和 IgG3 是主要涉及的亚类。本研究显示 IgG-RF 和 IgG3 的同时存在,支持了该亚类参与 CGs 早期阶段启动的假说。
我们描述了 6 例 HCV 阳性患者的病例系列,所有患者均有周围神经病和短暂性脑缺血发作,表现为由 IgG3 和 IgG1 形成的冷沉淀。通过免疫固定电泳用针对 IgG1、IgG2、IgG3 和 IgG4 的抗血清对冷沉淀 IgG 亚类进行研究。
我们的 6 名患者表现出免疫化学模式特征,仅存在可能具有 RF 活性的 IgG1 和 IgG3 亚类,其中 6 名患者中的 1 名在其脑脊液中表现出单克隆 IgG3。
我们可以假设 IgG 通过血脑屏障的转移可能通过涉及两种亚类在鞘内血管中形成的循环免疫复合物沉淀的机制导致 TIA 的发生。