Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy
Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy
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DOI：
10.1016/j.biopsych.2005.04.026
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发表时间：
2005-09-15
影响因子：
10.6
通讯作者：
Slocumb, NL
中科院分区：
文献类型：
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作者：
Black, JL;Silber, MH;Slocumb, NL
背景：嗜睡症犬模型具有下丘脑分泌素受体 2 基因突变，前下丘脑泌素原敲除小鼠 V 系表现出嗜睡症样行为。人类发作性睡病伴猝倒与人类白细胞抗原 DQB1*0602 和脑脊液中下丘脑分泌素水平降低有关，表明存在自身免疫素质。我们测试了以下假设：患有猝倒的 DQB1*0602 阳性发作性睡病患者的免疫球蛋白 (Ig)G 对人前下丘脑泌素原及其裂解产物有反应。方法：研究了 41 名患有猝倒的 DQB1*0602 阳性发作性睡病患者和 55 名对照受试者的血清样本，以及 19 名发作性睡病患者和 13 份对照样本的脑脊液。我们使用免疫沉淀试验 (IP)、表达前下丘脑泌素原的中国仓鼠卵巢细胞的免疫荧光显微镜检查 (IF) 和蛋白质印迹，检测了与前下丘脑泌素原及其主要裂解产物（包括下丘脑泌素 1 和 2）反应的 IgG。 结果：通过 IP 测量，没有证据表明发作性睡病受试者的 CSF 中存在 IgG 与前下丘脑泌素原或其裂解产物反应。蛋白质印迹和 IF 虽然通过两种比较方法，CSF 和 C 端肽的 IP 显示出显着差异，但对照受试者的每分钟计数高于发作性睡病受试者，这与我们的假设相反。 结论：不支持 DQB1*0602 阳性发作性睡病受试者猝倒症具有与前下丘脑分泌素或其裂解产物反应的 IgG 的假设。
Background: Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine V lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1*0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products.Methods: Serum samples of 41 DQB1*0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots.Results: There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects bad higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis.Conclusions: The hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.