McLean R T, Wilson P, St Clair D, Mustard C J, Wei J
Division of Health Research, University of the Highlands and Islands, Centre for Health Science, Inverness, UK.
Centre for Rural Health, University of Aberdeen, Centre for Health Science, Inverness, UK.
Transl Psychiatry. 2017 May 9;7(5):e1121. doi: 10.1038/tp.2017.89.
Gluten consumption has previously been implicated in the development of schizophrenia while an immunological link between gluten and schizophrenia was established by the detection of circulating antibodies against gliadin, a major component of wheat gluten. Several studies have reported an increase in circulating antibodies against native gliadin molecules that are unlikely to survive degradation in the digestive system. In this study, therefore, we measured plasma immunoglobulin G (IgG) and IgA antibodies against indigestible gliadin-derived peptide antigens using an in-house enzyme-linked immunosorbent assay (ELISA) among 169 patients with schizophrenia and 236 control subjects. We also examined the plasma levels of IgG and IgA antibodies against the mixture of native gliadins using commercially available ELISA kits. The results showed that patients with schizophrenia had the increased levels of plasma IgG against the γ-gliadin-derived fragment, namely AAQ6C, but decreased levels of plasma IgG against the α- and γ3-gliadin-derived antigens, as compared with control subjects. This study also demonstrated a uniform decrease in plasma IgA antibodies against gliadin-derived antigens. There was no significant difference in the levels of plasma antibodies against native gliadins between the patient group and the control group. Of eight gliadin-derived antigens tested, four showed a sensitivity of >20% against the specificity of ⩾95% for detection of their corresponding antibodies in plasma. These four tests may thus have a potential to serve as biomarkers for the identification of schizophrenia subgroups that may need an alternative therapy or precision treatment. Further investigation with clinical trials should be carried out to explore this possibility.
先前已有研究表明,食用麸质与精神分裂症的发病有关,同时通过检测针对麦麸主要成分麦醇溶蛋白的循环抗体,建立了麸质与精神分裂症之间的免疫联系。多项研究报告称,针对天然麦醇溶蛋白分子的循环抗体有所增加,而这些分子在消化系统中不太可能在降解后存活。因此,在本研究中,我们使用内部酶联免疫吸附测定法(ELISA),对169例精神分裂症患者和236名对照受试者检测了针对难消化的麦醇溶蛋白衍生肽抗原的血浆免疫球蛋白G(IgG)和IgA抗体。我们还使用市售ELISA试剂盒检测了针对天然麦醇溶蛋白混合物的血浆IgG和IgA抗体水平。结果显示,与对照受试者相比,精神分裂症患者针对γ-麦醇溶蛋白衍生片段(即AAQ6C)的血浆IgG水平升高,但针对α-和γ3-麦醇溶蛋白衍生抗原的血浆IgG水平降低。本研究还表明,针对麦醇溶蛋白衍生抗原的血浆IgA抗体水平普遍下降。患者组和对照组之间针对天然麦醇溶蛋白的血浆抗体水平没有显著差异。在测试的八种麦醇溶蛋白衍生抗原中,有四种在检测血浆中相应抗体时,灵敏度>20%,特异性⩾95%。因此,这四项检测可能有潜力作为生物标志物,用于识别可能需要替代疗法或精准治疗的精神分裂症亚组。应通过临床试验进行进一步研究,以探索这种可能性。
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