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

自20世纪70年代中期以来，经典补体途径在低温下的体外活化已被接受为补体的冷活化（CA）（1）。我们已经证明这种激活与HCV感染密切相关（2）。补体可被低温下形成的免疫复合物激活，这可能与cryoclavulin有关。在有HCV抗体的患者中，RF阳性病例的发生率高于无HCV抗体的病例（3）。此外，显示冷激活的病例中RF阳性的发生率高于无冷激活的病例（3）。HCV抗体阳性和冷活化阳性的血清在低温储存期间显示RF升高的发生率较高（4），但通过添加豚鼠血清作为补体来源或在具有较高离子强度的缓冲液中抑制升高。在HCV感染的存在下，B淋巴细胞的一个亚群（或多个亚群）增殖，并且分泌特定类型RF的B细胞的一个克隆（或多个克隆）可以扩增。已经报道，在患有非霍奇金淋巴瘤（NHL）的组中HCV感染的发生率高，并且在NHL患者中可溶性白细胞介素-2受体（sIL-2 R）的血清水平升高，并且与肿瘤负荷相关。据报道，HCV相关的NHL并发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。我们检测了44例NHL和5例成人T细胞白血病患者的sIL-2 R和HCV。HCV抗体和/或HCV-RNA阳性率为33.0%。令人惊讶的是，与HCV阴性病例中的sIL-2 R水平相比，HCV阳性病例中的sIL-2 R水平显著低。HCV感染可引起特定淋巴细胞克隆的扩增和肿瘤转化。

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.