Novel immune response to gluten in individuals with schizophrenia.
Novel immune response to gluten in individuals with schizophrenia.
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DOI：
10.1016/j.schres.2009.08.009
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发表时间：
2010-05
影响因子：
4.5
通讯作者：
Alaedini, Armin
中科院分区：
文献类型：
--
作者：
Samaroo, Diana;Dickerson, Faith;Kasarda, Donald D.;Green, Peter H. R.;Briani, Chiara;Yolken, Robert H.;Alaedini, Armin
乳糜泻和精神分裂症之间的联系已经被假设了几年，主要是基于患者中醇溶蛋白抗体水平升高的报道。我们试图通过表征精神分裂症患者亚群中抗醇溶蛋白免疫反应的分子特异性和机制来检验精神分裂症和乳糜泻之间的拟议联系。对精神分裂症和抗醇溶蛋白抗体效价升高的患者的血液样本进行了乳糜泻相关生物标志物的检测，包括转谷氨酰胺酶2(TG2)酶和去胺化醇溶蛋白多肽的抗体，以及人类白细胞抗原-DQ2和-DQ8 MHC基因。通过检测对层析分离的面筋蛋白的反应性，进一步表征了抗醇溶蛋白抗体的反应。通过肽质量图谱鉴定目的蛋白。与乳糜泻患者相比，精神分裂症患者的抗醇溶蛋白免疫反应与抗TG2抗体或HLA-DQ2和-DQ8标志物之间没有发现关联。此外，大多数患有精神分裂症和抗醇溶蛋白抗体的人对去胺化的醇溶蛋白多肽没有抗体反应性。对抗体特异性的进一步鉴定表明，在精神分裂症和乳糜泻患者中，抗体对不同的面筋蛋白具有优先反应性。这些结果表明，精神分裂症患者的抗醇溶蛋白免疫反应具有不同于乳糜泻患者的抗原性，且与谷氨酰胺转氨酶和人类白细胞抗原DQ2/DQ8的作用无关。与此同时，特定面筋蛋白抗体水平的升高表明，精神分裂症患者的一部分患者存在共同的免疫异常。进一步表征和了解精神分裂症患者对面筋的免疫反应可能为特定疾病表型的发病机制提供新的见解。
A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antiboy did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes.
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