Amoroso A, Berrino M, Canale L, Cornaglia M, Guarrera S, Mazzola G, Savoldi S, Scolari F, Sällberg M, Clementi M, Gabrielli A
Servizio di Genetica, IRCCS Burlo Garofolo and Università di Trieste, Italy.
J Hepatol. 1998 Jul;29(1):36-44. doi: 10.1016/s0168-8278(98)80176-1.
BACKGROUND/AIMS: Hepatitis C virus infection is known to play an important role in the pathogenesis of essential mixed cryoglobulinemia type II. Progression of hepatitis C virus infection to mixed cryoglobulinemia may be influenced by host immune response. To analyze the immunogenetic background of mixed cryoglobulinemia, we studied HLA-DR, DQ loci and the switch regions of immunoglobulin heavy chain gamma1 and gamma4 constant genes.
HLA typing was performed in 84 hepatitis C virus-infected patients (46 with cryoglobulins and 38 without), and 109 healthy controls, through analysis of restriction fragment length polymorphisms, supplemented with other techniques. Immunoglobulin heavy chain gamma1 and gamma4 polymorphisms, detected by restriction fragment length polymorphisms, were studied in 41 patients with mixed cryoglobulinemia and 51 controls.
The gene frequency of DRB111 was significantly higher in patients with mixed cryoglobulinemia than in controls (0.36 and 0.20, respectively; p= 0.0035). However, DRB111 was also increased in the subgroup of patients without mixed cryoglobulinemia who did not develop severe liver disease, while it was decreased in those with severe liver damage (0.50 and 0.13; p=0.0035). The frequency of 5.4 kb allele of the immunoglobulin heavy chain gamma1 switch region was higher in patients with mixed cryoglobulinemia than in controls (0.47 and 0.22; pc=0.002), while the frequency of 5.5 kb allele was lower (0.51 and 0.78; pc= 0.001).
Susceptibility to develop cryoglobulins after hepatitis C virus infection was not associated with HLA-DR or DQ. HLA-DRB1*11-positive individuals were protected from serious chronic liver disease after hepatitis C virus infection. Immunoglobulin heavy chain constant gamma1 switch region restriction fragment length polymorphisms were associated with mixed cryoglobulinemia.
背景/目的：已知丙型肝炎病毒感染在II型原发性混合性冷球蛋白血症的发病机制中起重要作用。丙型肝炎病毒感染进展为混合性冷球蛋白血症可能受宿主免疫反应影响。为分析混合性冷球蛋白血症的免疫遗传背景，我们研究了HLA - DR、DQ基因座以及免疫球蛋白重链γ1和γ4恒定基因的转换区。
通过限制性片段长度多态性分析并辅以其他技术，对84例丙型肝炎病毒感染患者（46例有冷球蛋白血症，38例无）和109例健康对照进行HLA分型。通过限制性片段长度多态性检测免疫球蛋白重链γ1和γ4多态性，对41例混合性冷球蛋白血症患者和51例对照进行研究。
混合性冷球蛋白血症患者中DRB111的基因频率显著高于对照组（分别为0.36和0.20；p = 0.0035）。然而，在未发生混合性冷球蛋白血症且未发展为严重肝病的患者亚组中DRB111也增加，而在有严重肝损伤的患者中则降低（0.50和0.13；p = 0.0035）。免疫球蛋白重链γ1转换区5.4 kb等位基因的频率在混合性冷球蛋白血症患者中高于对照组（0.47和0.22；pc = 0.002），而5.5 kb等位基因的频率较低（0.51和0.78；pc = 0.001）。
丙型肝炎病毒感染后发生冷球蛋白血症的易感性与HLA - DR或DQ无关。HLA - DRB1*11阳性个体在丙型肝炎病毒感染后可免受严重慢性肝病影响。免疫球蛋白重链恒定γ1转换区限制性片段长度多态性与混合性冷球蛋白血症相关。
