IMMUNE RESPONSES IN PATIENTS WITH GBS AND CIDP

急性格林-巴利综合征(GBS)和慢性炎症性脱髓鞘多神经病(CIDP)是人类获得性脱髓鞘疾病，病因和发病机制不明。许多证据表明，在这些疾病中，组织损伤的免疫学机制通常是由GBS的感染触发的。血浆置换在GBS和CIDP中确立的治疗效果表明，自身抗体或循环免疫因子在这些疾病的发病机制中起着至关重要的作用。最近的证据表明，GM1、LM1、GD1a和GT1b等主要酸性糖脂是大约一半的GBS患者的重要抗原。然而，大多数其他GBS患者的抗原特异性仍不清楚。我们发现，部分GBS患者对GT1b有反应，GT1b是一种轻微的神经节苷脂。我们假设GBS患者中的抗原与主要神经节苷脂不起反应，是次要的，至今还没有很好地表征糖脂或蛋白质/糖蛋白。这项研究的具体目的是鉴定和表征GBS患者中没有表现出针对主要神经节苷脂抗原的自身抗体的糖脂和蛋白质抗原。我们建议检测大量格林-巴利综合征、慢性阻塞性肺疾病和正常人的血清，以检测蛋白质和少量糖脂抗原的自身抗体，并提纯和鉴定可能的蛋白质或糖脂抗原(S)。PAGE-Western印迹、酶联免疫吸附试验(ELISA)和薄层层析免疫染色将用于检测抗神经抗体。将对GBS和CIDP患者的早期和系列血清样本进行检测，以确定自身抗体效价是否与疾病严重程度相关。

Acute Guillain-Barr syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are acquired human demyelinating diseases of the unknown etiology and pathogenesis. Much evidence points to immunological mechanisms of tissue injury in these diseases often following an infectious trigger in GBS. The established therapeutic efficacy of plasmapheresis in GBS and CIDP suggests that autoantibodies or circulating immune factors are paramount in the pathogenesis of these disorders. Recent evidence indicates that major acidic glycolipids such as GM1, LM1, GD1a and GT1b are important antigens in about half of the patients with GBS. However, the antigenic specificity in most of the other GBS patients remains unknown. We have found that a proportion of patients with GBS react with GT1b, a minor ganglioside. We hypothesize that the antigens in the GBS patients not reactive with major gangliosides, are minor as yet not well characterized glycolipids or proteins/glycoproteins. The specific aim of this study is identify and characterize glycolipid and protein antigens in GBS patients that do not exhibit autoantibodies against major ganglioside antigens. We propose to test sera from a large number of patients with GBS, CIDP and controls, for autoantibodies to proteins and minor glycolipid antigens, and to purify and characterize the putative protein or glycolipid antigen(s). PAGE-Western blotting, enzyme linked immunosorbent assay (ELISA) and thin-layer chromatogram-immunostaining will be used to test for antineural antibodies. Early and serial serum specimens from GBS and CIDP patients will be examined to see whether autoantibody titers correlate with disease severity.