Sansonno D, Lauletta G, Nisi L, Gatti P, Pesola F, Pansini N, Dammacco F
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
Clin Exp Immunol. 2003 Aug;133(2):275-82. doi: 10.1046/j.1365-2249.2003.02204.x.
Hepatitis C virus (HCV) infection has been detected in a large proportion of patients with mixed cryoglobulinaemia (MC). Circulating 'free' non-enveloped HCV core protein has been demonstrated in HCV-infected patients, and this suggests its possible involvement in the formation of cryoprecipitable immune complexes (ICs). Thirty-two anti-HCV, HCV RNA-positive patients with type II MC were evaluated. Non-enveloped HCV core protein, HCV RNA sequences, total IgM, rheumatoid factor (RF) activity, IgG and IgG subclasses, C3 and C4 fractions, C1q protein and C1q binding activity were assessed in both cryoprecipitates and supernatants. Non-enveloped HCV core protein was demonstrated in 30 of 32 (93.7%) type II MC patients. After separation of cold-precipitable material, the protein was removed completely from supernatant in 12 patients (40%), whereas it was enriched in the cryoprecipitates of the remaining 18. In addition, HCV RNA and IgM molecules with RF activity were concentrated selectively in the cryoprecipitates. Differential precipitation was found for both total IgG and IgG subclasses, as they were less represented in the cryoglobulins and no selective enrichment was noted. Immunological characterization of HCV core protein-containing cryoprecipitating ICs after chromatographic fractionation showed that the IgM monoclonal component had RF activity, whereas anti-HCV core reactivity was confined to the IgG fraction. C1q enrichment in addition to high avidity of ICs for C1q binding in the cryoprecipitates suggest that complement activation may occur through the C1q protein pathway. The present data demonstrate that non-enveloped HCV core protein is a constitutive component of cryoprecipitable ICs in type II MC patients.
在大部分混合性冷球蛋白血症（MC）患者中已检测到丙型肝炎病毒（HCV）感染。在HCV感染患者中已证实存在循环“游离”非包膜HCV核心蛋白，这表明其可能参与可冷沉淀免疫复合物（ICs）的形成。对32例抗HCV、HCV RNA阳性的II型MC患者进行了评估。在冷沉淀物和上清液中评估了非包膜HCV核心蛋白、HCV RNA序列、总IgM、类风湿因子（RF）活性、IgG和IgG亚类、C3和C4组分、C1q蛋白及C1q结合活性。32例II型MC患者中有30例（93.7%）检测到非包膜HCV核心蛋白。分离冷可沉淀物质后，12例患者（40%）的上清液中该蛋白被完全去除，而其余18例患者的冷沉淀物中该蛋白富集。此外，具有RF活性的HCV RNA和IgM分子选择性地集中在冷沉淀物中。总IgG和IgG亚类均存在差异沉淀，因为它们在冷球蛋白中的含量较少，且未观察到选择性富集。对经色谱分离的含HCV核心蛋白的冷沉淀ICs进行免疫表征显示，IgM单克隆成分具有RF活性，而抗HCV核心反应性局限于IgG组分。冷沉淀物中除了ICs对C1q结合具有高亲和力外，C1q也有富集，这表明补体激活可能通过C1q蛋白途径发生。目前的数据表明，非包膜HCV核心蛋白是II型MC患者可冷沉淀ICs的组成成分。
