病毒分子模拟介导多发性硬化发病机制的初步分析

Preliminary study on the relationship between molecular mimicry and the immunopathogenesis of multiple sclerosis

目的研究多发性硬化(MS)患者所具有的与人类疱疹病毒6型(HHV-6)病毒/人类疱疹病毒4型病毒(EBV)和髓鞘碱性蛋白(MBP)发生交叉反应的CD4+/CD8+T细胞,以及MS患者血清和脑脊液中MBP和抗病毒抗体表达状况,探讨MS发病与HHV-6/EBV感染的关系。方法通过氚标记胸腺嘧啶核苷(3H-TdR)掺入实验分析HHV-6/EBV病毒肽和MBP肽段诱导的MS患者CD4+和CD8+T细胞的应答反应,以高灵敏ELISA试剂盒检测MS患者脑脊液和血清中抗HHV-6/EBV抗体水平,并以引物序列特异的PCR(SSP-PCR)技术分析MS患者HLA-Ⅱ类分子DRB1的表达格局。结果 (1)MS患者HLA-Ⅱ类分子DRB1*04基因(41.7%)与健康对照组(18.7%)相比具有较高的检出率,但差异无统计学意义(P>0.05)。(2)MS患者血清中存在高水平抗HHV-6抗体,同时亦可检测出抗EBV壳蛋白抗原(VCA)IgG抗体和EBV核抗原-1(EBNA-1)的IgG抗体。(3)3H-TdR掺入实验结果表明,MS患者的CD4+T细胞或CD8+T细胞对自身MBP肽段及合成的HHV-6/EBV肽段的诱导作用均存在交叉反应。结论 HHV-6/EBV与MS患者MBP自身抗原存在结构上的同源性。该同源性可诱发MS患者自身反应性CD4+/CD8+T细胞活化而导致MS患者免疫损伤,可能是MS的发病机制之一。

Objective To detect the HHV-6/EBV and myelin basic protein （MBP） cross reactive CD4＋/CD8＋ T cell, HHV-6/EBV autoantibodies and MBP in serum and cerebrospinal fluid in multiple sclerosis （MS） patients. To clarify the effects of HHV-6/EBV infection in the pathogenesis of MS. Methods Viral and MBP peptides were used to induce the proliferation of CD4＋ and CD8＋ T cells by the s H-TdR test. HLA-H molecular （DRB1） was detected by SSP-PCR, HHV-6/EBV autoantibodies and MBP were detected by ELISA in the serum and cerebrospinal fluid in MS patients. Results （1） The expression of HLA-DRBl＋ 04 was higher in MS patients （41.7 %） compared with the healthy controls （18.7 %）, but did not reach significant difference （P 〉0.05）. （2） The serum levels of HHV-6, VCA and EBNA-1 IgG autoantibodies increased significantly in the MS patients . （3） A significant cross-reaction between MBP81-gs and MBP83-89/HHV-6/EBV in CD4＋/CD8＋ T cells was found. Conclusions There is structure homology between HHV-6/EBV and MBP in MS patients, which may activate auto-reactive CD4＋/CD8＋ T cells and then contribute to the pathogenesis of MS.