Elucidation of complement cold activation and cryoglobulin formation associated with HCV infection.

自20世纪70年代中期S以来，经典补体途径的低温体外激活被认为是补体的冷激活(CA)(1)。我们已经证明这种激活与丙型肝炎病毒感染密切相关(2)。补体可能被低温下形成的免疫复合体激活，这可能与冷冻球蛋白有关。丙型肝炎病毒抗体阳性组的RF阳性例数高于无抗体组(3)。此外，有冷激活的病例中RF阳性的发生率高于无冷激活的病例(3)。丙型肝炎病毒抗体阳性和冷激活阳性的血清在低温保存过程中RF升高的发生率较高(4)，但添加豚鼠血清作为补体或在较高离子强度的缓冲液中可抑制这种升高。在存在丙型肝炎病毒感染的情况下，一个(或多个)B淋巴细胞亚群增殖，一个(或多个)B细胞克隆(或克隆)分泌特定类型的RF。据报道，在非霍奇金淋巴瘤(NHL)患者中，丙型肝炎病毒感染的发生率很高，而且NHL患者血清中可溶性白细胞介素2受体(sIL-2R)水平升高，并与肿瘤负担有关。另据报道，丙型肝炎病毒相关的非霍奇金淋巴瘤合并混合性冷球蛋白血症代表了特定患者的亚群，其中也可能涉及特定的遗传和/或环境因素。对44例非霍奇金淋巴瘤患者和5例成人T细胞白血病患者进行了sIL-2R和丙型肝炎病毒检测。丙型肝炎病毒抗体和(或)丙型肝炎病毒核糖核酸阳性者占330%。令人惊讶的是，与丙型肝炎病毒阴性患者相比，丙型肝炎病毒阳性患者的sIL-2R水平显著降低。丙型肝炎病毒感染可能导致特定克隆淋巴细胞的扩张和肿瘤性转化。

Since the mid 1970's the in vitro activation of the classical complement pathway at a low temperature has been accepted as cold activation (CA) of the complement (1). We have proved that this activation is strongly associated with HCV infection (2). The complement may be activated by an immune complex formed at a low temperature and this may be related to cryoglobulin. The incidence of positive cases for RF among patients with HCV antibody was higher than among cases without HCV antibody (3). In addition, the incidence of RF positivity among cases showing cold activation was higher than among those with no cold activation (3). Sera of HCV antibody positive and cold activation positive showed a high incidence of elevation of RF during storage at low temperature (4) but the elevation was suppressed by addition of guinea pig serum as a complement source or in a buffer with a higher ionic strength. In the presence of HCV infection, a subset (or subsets) of B-lymphocytes proliferates and a clone (or clones) of B-cells excreting a particular type of RF may expand.It has been reported that the incidence of HCV infection is high in a group with non-Hodgkin's lymphoma (NHL) and serum levels of soluble interleukin-2 receptors (slL-2R) are increased in NHL patients and relate to the tumor burden. It has also been reported that HCV-related NHL complicating mixed cryoglobulinaemia represents a particular patient's subset in which particular genetic and / or environmental factors can also be involved. We measured slL-2R, and HCV in 44 NHL and 5 adult T cell leukemia patients. HCV antibody and/or HCV-RNA were positive in 330% cases. Surprisingly, the levels of slL-2R in HCV positive cases were significantly low when compared to those in HCV negative cases. HCV infection may cause expansion and neoplastic transformation of a particular clone of lymphocytes.