Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase
Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase
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DOI：
10.1002/ana.21450
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发表时间：
2008-09-01
影响因子：
11.2
通讯作者：
Aeschlimann, Daniel
中科院分区：
文献类型：
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作者：
Hadjivassiliou, Marios;Aeschlimann, Pascale;Aeschlimann, Daniel
目的：面筋敏感通常表现为乳糜泻，一种由自身免疫介导的慢性小肠疾病。在这些患者中，神经系统疾病发生的频率高达10%。然而，神经功能障碍也可能是面筋敏感性的唯一表现特征。针对谷氨酰胺转氨酶基因家族不同成员的自身免疫的发展可以解释面筋敏感表现的多样性。我们鉴定了一种新的神经元转谷氨酰胺酶同工酶，并研究了该酶是否是神经功能障碍患者免疫反应的靶点。方法：利用重组人转谷氨酰胺酶，建立了酶联免疫吸附试验和抑制试验，分析了面筋敏感型胃肠道疾病和神经系统疾病患者的血清标本，以及包括无关遗传或免疫条件的自身抗体的存在和特异性。结果：虽然抗转谷氨酰胺酶2 IgA的发生与胃肠道疾病有关，但抗转谷氨酰胺酶6的抗体和IgA反应在面筋蛋白共济失调中普遍存在，与肠道受累无关。这种抗体在有明确遗传来源的共济失调或健康的个体中是不存在的。抑制研究表明，在那些共济失调和肠病患者中，不同的抗体群体与两种不同的转谷氨酰胺酶同工酶反应。此外，对脑组织的尸检分析显示，小脑中有含有转谷氨酰胺酶6的IgA沉积。解释：除了检测人类白细胞抗原类型以及检测抗醇溶蛋白和抗转谷氨酰胺酶2抗体外，转谷氨酰胺酶6抗体还可以作为标记，以确定可能有患神经疾病风险的面筋敏感型患者的亚群。
Objective: Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity. Development of autoimmunity directed toward different members of the transglutaminase gene family could offer an explanation for the diversity in manifestations of gluten sensitivity. We have identified a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.Methods: Using recombinant human transglutaminases, we developed enzyme-linked immunosorbent assays and inhibition assays to analyze serum samples of patients with gluten-sensitive gastrointestinal and neurological disorders, and various control groups including unrelated inherited or immune conditions for the presence and specificity of autoantibodies.Results: Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement. Such antibodies are absent in ataxia of defined genetic origin or in healthy individuals. Inhibition studies showed that in those patients with ataxia and enteropathy, separate antibody populations react with the two different transglutaminase isozymes. Furthermore, postmortem analysis of brain tissue showed cerebellar IgA deposits that contained transglutaminase 6.Interpretation: Antibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and detection of anti-gliadin and anti-transglutaminase 2 antibodies to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease.