Cacoub P, Musset L, Amoura Z, Guilani P, Chabre H, Lunel F, Poynard T, Opolon P, Piette J C
Department of Internal Medicine, Hôpital La Pitié-Salpêtrière, Paris, France.
J Rheumatol. 1997 Nov;24(11):2139-44.
To investigate anticardiolipin antibodies (aCL), anti-beta2-glycoprotein I (anti-beta2GPI), and antinucleosome antibodies in patients with hepatitis C virus (HCV) with or without mixed cryoglobulinemia. aCL can appear in infectious diseases, but are not then associated with thrombotic events. Antibodies directed to beta2GPI, a co-factor of aCL, have been said to be associated with the presence of "autoimmune" aCL. About 50% of cases of essential mixed cryoglobulinemia are associated with HCV infection. High prevalence of autoantibodies directed to nuclear antigens has been found in HCV infection but the prevalence of antibody to nucleosome has not yet been reported.
Group 1: 29 patients with chronic HCV infection and mixed cryoglobulinemia. Group 2: 17 patients with chronic HCV infection but without mixed cryoglobulinemia. To analyze the possible effect of mixed cryoglobulinemia itself on aCL production, we also studied 22 patients with essential mixed cryoglobulinemia and no HCV infection (Group 3). In addition, 96 healthy blood donors were used as a control group (Group 4). Mixed cryoglobulinemia was detected by immunofixation. Anti-HCV antibodies were detected by 3rd generation tests, aCL, anti-beta2GPI, and antinucleosorne antibodies were detected by ELISA. In patients with mixed cryoglobulinemia, we also looked for aCL separately in cryoprecipitate and in serum after extraction of mixed cryoglobulins to investigate a possible "capture" of aCL in the cryoprecipitate.
IgG aCL were more frequently found in patients with HCV than in controls [9/46 (20%) vs 2/96 (2%); p < 0.001]. The prevalence of aCL was similar in patients with HCV with or without mixed cryoglobulinemia (6/29 vs 3/17; p = NS). No patient with positive aCL had anti-beta2GPI, antinucleosome antibodies, thrombotic events, or thrombocytopenia. IgG aCL were more frequent in patients with mixed cryoglobulinemia, whatever their status for HCV infection, than in subjects without mixed cryoglobulinemia [8/51 (16%) vs 5/113 (4%); p < 0.02]. The prevalence of aCL was similar in patients with type II or type III mixed cryoglobulinemia. When we looked for aCL separately in serum and in cryoprecipitate, we did not find aCL in cryoprecipitate. In patients with HCV, the prevalence of aCL was not different whether patients were treated or not with interferon alpha.
IgG aCL are frequently found in patients with HCV regardless of status for mixed cryoglobulinemia. These aCL have the characteristics of infection related aCL: low titer, absence of thrombotic events, and absence of anti-beta2GPI. The high proportion of aCL in patients with mixed cryoglobulinemia compared to those without, and the absence of antinucleosome antibodies, suggest that these aCL may be secondary to endothelial damage induced by mixed cryoglobulinemia or HCV itself, rather than to nonspecific polyclonal lymphocyte activation.
研究丙型肝炎病毒（HCV）感染患者无论有无混合性冷球蛋白血症时的抗心磷脂抗体（aCL）、抗β2糖蛋白I（抗β2GPI）及抗核小体抗体。aCL可出现在感染性疾病中，但此时与血栓形成事件无关。针对aCL的辅助因子β2GPI的抗体被认为与“自身免疫性”aCL的存在有关。约50%的原发性混合性冷球蛋白血症病例与HCV感染有关。在HCV感染中已发现针对核抗原的自身抗体患病率较高，但抗核小体抗体的患病率尚未见报道。
第1组：29例慢性HCV感染合并混合性冷球蛋白血症患者。第2组：17例慢性HCV感染但无混合性冷球蛋白血症患者。为分析混合性冷球蛋白血症本身对aCL产生的可能影响，我们还研究了22例原发性混合性冷球蛋白血症且无HCV感染的患者（第3组）。此外，96名健康献血者作为对照组（第4组）。通过免疫固定法检测混合性冷球蛋白血症。采用第三代检测法检测抗HCV抗体，通过ELISA检测aCL、抗β2GPI及抗核小体抗体。在混合性冷球蛋白血症患者中，我们还分别在冷沉淀物及提取混合性冷球蛋白后的血清中查找aCL，以研究冷沉淀物中是否可能“捕获”aCL。
HCV感染患者中IgG aCL的检出率高于对照组[9/46（20%）对2/96（2%）；p<0.001]。有无混合性冷球蛋白血症的HCV感染患者中aCL的患病率相似（6/29对3/17；p=无统计学意义）。aCL阳性的患者均无抗β2GPI、抗核小体抗体、血栓形成事件或血小板减少症。无论HCV感染状态如何，混合性冷球蛋白血症患者中IgG aCL的检出率均高于无混合性冷球蛋白血症的患者[8/51（16%）对5/113（4%）；p<0.02]。II型或III型混合性冷球蛋白血症患者中aCL的患病率相似。当我们分别在血清和冷沉淀物中查找aCL时，在冷沉淀物中未发现aCL。在HCV感染患者中，无论是否接受干扰素α治疗，aCL的患病率无差异。
无论混合性冷球蛋白血症状态如何，HCV感染患者中常可发现IgG aCL。这些aCL具有感染相关aCL的特征：低滴度、无血栓形成事件且无抗β2GPI。与无混合性冷球蛋白血症的患者相比，混合性冷球蛋白血症患者中aCL比例较高且无抗核小体抗体，提示这些aCL可能继发于混合性冷球蛋白血症或HCV本身诱导的内皮损伤，而非非特异性多克隆淋巴细胞激活。
