Lenzi M, Frisoni M, Mantovani V, Ricci P, Muratori L, Francesconi R, Cuccia M, Ferri S, Bianchi F B
Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Istituto di Ematologia, Universita di Bologna, Policlinico S. Orsola, Bologna, Italia.
Blood. 1998 Mar 15;91(6):2062-6.
Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10. 1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected = .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.
我们的目的是研究宿主遗传因素是否参与丙型肝炎病毒（HCV）相关混合性冷球蛋白血症（MC）的发病。我们通过体格检查、血液化学检查、冷球蛋白及其成分评估、非器官特异性自身抗体、抗HCV抗体、血清HCV RNA和HLA多态性研究了25例呈现典型MC临床表现的连续患者。部分患者还进行了肝脏、骨髓和小唾液腺活检。将HLA结果与正常对照以及无MC且自身免疫现象阴性的慢性HCV感染患者（病理对照）的结果进行比较。25例患者中有14例（56%）为II型MC，其余11例（44%）为III型MC。所有患者的抗HCV抗体和/或血清HCV RNA均为阳性。25例患者中有40%（10例）检测到HLA - B8，而正常对照中这一比例为10.1%（377例中的38例）（P = .00003，校正后P = .0005，相对危险度[RR] 5.9），病理对照中为6.7%（30例中的2例）（P = .007，校正后P无显著性差异）。至于II类HLA分子，只有DR3在MC患者中（40%，25例中的10例）比正常对照（15.1%，377例中的57例）显著更常见（P = .003，校正后P = .03，RR 3.7）。对B8和/或DR3阳性患者发生MC的风险计算比值比（OR），在同时拥有两者的个体中观察到最高的OR（8.2）。结果表明，HCV相关MC的发生与HLA - B8和DR3标记物有关。
