Cacoub P, Bourlière M, Hausfater P, Charlotte F, Khiri H, Toci S, Piette J C, Poynard T, Halfon P
Service de médecine interne, Hopital La Pitié-Salpêtrière, Bd de l'Hôpital, Paris Cedex, France.
J Viral Hepat. 2003 Jan;10(1):10-5. doi: 10.1046/j.1365-2893.2003.00380.x.
Chronic hepatitis C virus (HCV) infection is frequently associated with type II mixed cryoglobulinaemia (MC), a benign lymphoproliferative disease (LPD). More recently, HCV has been implicated as a possible aetiologic factor of B-cell non-Hodgkin lymphoma (B-NHL). CD81, a B-cell surface receptor, has been proposed as a receptor for HCV binding and entry in circulating B cells. The stimulation of CD81 complex enables B cells to respond to lower concentrations of antigen and finally induces B-cell proliferation. We studied the phenotypic expression of CD81, CD19 and CD5 on circulating B cells in HCV patients LPD-positive or LPD-negative. Sixty-two patients were anti-HCV antibody positive. Among HCV positive patients, 44 were HCV RNA positive with an histologically proven chronic active hepatitis of whom 10 had a B-NHL, 14 an MC and 24 no extrahepatic manifestation. Eighteen patients were HCV RNA negative with evidence of resolved infection. A control group included 40 healthy subjects. Peripheral blood mononuclear cells (PBMC) were stained for surface expression of CD81, CD19 and CD5 using monoclonal antibodies, and were analyzed by flow cytometry. The percentage of PBMC expressing CD81, CD19 and CD5 receptors were compared between the groups by univariate analysis. Logistic regression model variables were then evaluated to correlate the presence of an LPD with HCV infection characteristics (i.e. age, gender, genotype, duration of infection, HCV RNA positivity, liver histological lesions), or phenotypic expression of CD81, CD19 and CD5 receptors on PBMC. HCV antibody-positive compared with HCV-negative subjects had a higher expression of CD19 receptor (23 +/- 13 vs 13 +/- 1%, P = 0.003). Among HCV RNA positive-patients, LPD+ compared with LPD- patients had a lower expression of CD81 (58 +/- 28 vs 82 +/- 18%, P = 0.001) and CD5 receptor (66 +/- 16 vs 74 +/- 13%, P = 0.04). In multivariate analysis, the expression of CD81 receptor was a negative (OR = 0.15, 95% CI = 0.04-0.64, P = 0.01) and CD19 receptor a positive (OR = 4.81, 95% CI =1.29-17.88, P = 0.02) predictive factor for an LPD. We found two negative predictive factors for HCV RNA positivity, i.e. age (OR = 0.23, 95% CI. = 0.08-0.62, P = 0.003) and the expression of CD81 receptor (OR = 0.34, 95% CI = 0.13-0.89, P = 0.02). In patients with a chronic active HCV infection, the presence of a lymphoproliferative disease, either MC or B-NHL, is associated with lower expression of CD81 and higher expression of CD19 receptor on peripheral B cells.
慢性丙型肝炎病毒（HCV）感染常与II型混合性冷球蛋白血症（MC）相关，后者是一种良性淋巴增殖性疾病（LPD）。最近，HCV被认为可能是B细胞非霍奇金淋巴瘤（B-NHL）的病因。CD81是一种B细胞表面受体，已被提出作为HCV在循环B细胞中结合和进入的受体。CD81复合物的刺激使B细胞能够对较低浓度的抗原作出反应，并最终诱导B细胞增殖。我们研究了HCV患者（LPD阳性或LPD阴性）循环B细胞上CD81、CD19和CD5的表型表达。62例患者抗HCV抗体呈阳性。在HCV阳性患者中，44例HCV RNA阳性，经组织学证实为慢性活动性肝炎，其中10例患有B-NHL，14例患有MC，24例无肝外表现。18例患者HCV RNA阴性，有感染已清除的证据。一个对照组包括40名健康受试者。使用单克隆抗体对外周血单个核细胞（PBMC）进行CD81、CD19和CD5表面表达染色，并通过流式细胞术进行分析。通过单因素分析比较各组中表达CD81、CD19和CD5受体的PBMC百分比。然后评估逻辑回归模型变量，以将LPD的存在与HCV感染特征（即年龄、性别、基因型、感染持续时间、HCV RNA阳性、肝脏组织学病变）或PBMC上CD81、CD19和CD5受体的表型表达相关联。与HCV阴性受试者相比，HCV抗体阳性者CD19受体表达更高（23±13%对13±1%，P = 0.003）。在HCV RNA阳性患者中，LPD+患者与LPD-患者相比，CD81表达较低（58±28%对82±18%，P = 0.001），CD5受体表达较低（66±16%对74±13%，P = 0.04）。在多因素分析中，CD81受体的表达是LPD的负性预测因素（OR = 0.15，95%CI = 0.04 - 0.64，P = 0.01），而CD19受体是正性预测因素（OR = 4.81，95%CI = 1.29 - 17.88，P = 0.02）。我们发现了两个HCV RNA阳性的负性预测因素，即年龄（OR = 0.23，95%CI = 0.08 - 0.62，P = 0.003）和CD81受体的表达（OR = 0.34，95%CI = 0.13 - 0.89，P = 0.02）。在慢性活动性HCV感染患者中，淋巴增殖性疾病（MC或B-NHL）的存在与外周B细胞上CD81表达降低和CD19受体表达升高相关。
