Fattovich G, Vinante F, Giustina G, Morosato L, Alberti A, Ruol A, Pizzolo G
Istituto di Semeiotica e Nefrologia Medica, University of Verona, Italy.
Clin Exp Immunol. 1996 Jan;103(1):105-10. doi: 10.1046/j.1365-2249.1996.915607.x.
There is evidence that both cellular and humoral components of the immune response are required for viral clearance to occur in chronic hepatitis B. Recent studies demonstrated that CD30 molecule, a member of the tumour necrosis factor superfamily of membrane cytokine receptors, is expressed on, and released as a soluble molecule (sCD30) by activated T cells producing T helper 2 (Th2) cytokines, which modulate antibody responses. To better characterize the immunoregulatory mechanisms in chronic hepatitis B virus (HBV) infection, sCD30 values were evaluated by an ELISA in 90 hepatitis B surface (HBsAg)-positive patients with chronic hepatitis, selected on the basis of active viral replication and biochemical activity. At presentation abnormal levels (> 20 U/ml) of sCD30 were detected in 57 (63%) out of 90 patients with chronic hepatitis B, and median value was significantly higher in this group of patients compared with that of healthy HBsAg carriers (26.7 versus 10.5 U/ml, P < 0.000 05) and with normal controls (26.7 versus 3 U/ml P < 0.000 01). Sequential studies of chronic hepatitis B did confirm the association of raised sCD30 levels with the active phase of the illness. On the other hand, a significant decrease was noted when sCD30 levels at diagnosis and after termination of HBV replication and biochemical remission of hepatitis were compared in 10 untreated patients (median, 28 U/ml at entry versus 8 U/ml at remission, P < 0.01) and in six patients responding to interferon-alpha therapy (median, 29.5 U/ml at entry versus 6 U/ml at remission, P < 0.05). The high serum sCD30 levels reported during the active phase of HBsAg-positive chronic hepatitis suggest a certain degree of immune competence of these patients, at least with respect to a Th2-type response. These data are in agreement with recent serologic surveys showing that most chronic hepatitis B patients do demonstrate ongoing humoral immune response to HBV antigens, using novel immunoassays designed to detect antibody in the presence of excess serum viral antigen. Th2 functions that mainly promote humoral immunity to HBV antigens may be critical, in association with a competent virus-specific cytotoxicity, for efficient termination of HBV replication in chronic hepatitis B.
有证据表明，慢性乙型肝炎病毒清除需要免疫反应的细胞和体液成分共同参与。最近的研究表明，CD30分子是膜细胞因子受体肿瘤坏死因子超家族的成员，由产生辅助性T细胞2（Th2）细胞因子的活化T细胞表达并作为可溶性分子（sCD30）释放，这些细胞因子可调节抗体反应。为了更好地描述慢性乙型肝炎病毒（HBV）感染中的免疫调节机制，采用酶联免疫吸附测定（ELISA）对90例慢性乙型肝炎表面抗原（HBsAg）阳性患者的sCD30值进行了评估，这些患者是根据病毒活跃复制和生化活性挑选出来的。就诊时，90例慢性乙型肝炎患者中有57例（63%）检测到sCD30水平异常（>20 U/ml），与健康HBsAg携带者组（26.7对10.5 U/ml，P<0.000 05）及正常对照组（26.7对3 U/ml，P<0.000 01）相比，该组患者的中位数水平显著更高。对慢性乙型肝炎的系列研究确实证实了sCD30水平升高与疾病的活动期相关。另一方面，在10例未经治疗的患者（中位数，入组时28 U/ml，缓解时8 U/ml，P<0.01）和6例对α干扰素治疗有反应的患者（中位数，入组时29.5 U/ml，缓解时6 U/ml，P<0.05）中，比较诊断时及HBV复制终止和肝炎生化缓解后的sCD30水平，发现有显著下降。HBsAg阳性慢性肝炎活动期报告的高血清sCD30水平表明这些患者具有一定程度的免疫能力，至少在Th2型反应方面如此。这些数据与最近的血清学调查结果一致，这些调查表明，使用旨在在存在过量血清病毒抗原的情况下检测抗体的新型免疫测定法，大多数慢性乙型肝炎患者确实表现出对HBV抗原持续的体液免疫反应。主要促进对HBV抗原体液免疫的Th2功能，与有效的病毒特异性细胞毒性相关，可能对慢性乙型肝炎中HBV复制的有效终止至关重要。
