IMMUNE RESPONSES IN PATIENTS WITH GBS AND CIDP

急性格林-巴尔综合征（GBS）和慢性炎症性脱髓鞘多神经病变（CIDP）是病因和发病机制尚不清楚的获得性人类脱髓鞘疾病。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在GBS的感染触发之后。血浆置换治疗GBS和CIDP的疗效表明，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，主要的酸性糖脂如GM1、LM1、GD1a和GT1b是大约一半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然未知。我们发现一部分GBS患者与GT1b（一种次要神经节苷脂）发生反应。我们假设GBS患者的抗原不与主要神经节苷类反应，是次要的，尚未被很好地表征的糖脂或蛋白质/糖蛋白。本研究的具体目的是鉴定和表征GBS患者中不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GBS、CIDP和对照组患者的血清中蛋白质和少量糖脂抗原的自身抗体，并纯化和表征推定的蛋白质或糖脂抗原。使用PAGE-Western blotting，酶联免疫吸附试验（ELISA）和薄层色谱-免疫染色检测抗神经抗体。将对GBS和CIDP患者的早期和连续血清标本进行检查，以确定自身抗体滴度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.