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首页> 外文期刊>International journal of immunopathology and pharmacology. >Allelic frequencies of 3' Ig heavy chain locus enhancer HS1,2-A associated with Ig levels in patients with schizophrenia
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Allelic frequencies of 3' Ig heavy chain locus enhancer HS1,2-A associated with Ig levels in patients with schizophrenia

机译：精神分裂症患者3'Ig重链基因座增强子HS1,2-A的等位基因频率与Ig水平相关

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摘要

Infectious and autoimmune pathogenic hypotheses of schizophrenia have been proposed, prompting searches for antibodies against viruses or brain structures, and for altered levels of immunoglobulins. Previous experiments have shown that allele frequencies of the Ig heavy chain 3′ enhancer HS1,2*A are associated with several autoimmune diseases, suggesting a possible correlation between HS1,2 alleles and Ig production. To test this, we analyzed levels of serum Igs and HS1,2*A genotypes in two independent cohorts, one of 88 schizophrenic inpatients (24 women) and a second of 133 healthy subjects (59 women). Both groups were similar in the frequency of individuals with altered serum concentration of Ig classes and IgG subclasses (schizophrenia panel-80%; controls-68%). With the possible exception of a stabilizing effect of olanzapine, no psychopharmacological drug consumed during the month prior to serum sampling in the schizophrenia group significantly affected Ig levels. In both patient and control cohorts, an increased frequency of the HS1,2*2A allele corresponded to increased Ig plasma levels, while an increased frequency of the HS1,2*1A affele corresponded to decreased Ig plasma levels. EMSA analysis with nuclear extracts from human B cells showed that the transcription factor SP1 bound to the polymorphic region of both HS1,2*1A and HS1,2*2A while NF-κB bound only to the HS1,2*2A. We predict that differences in transcription factor binding sites in the two allelic variants of the 3′ IgH enhancer HS1,2 may provide a mechanism by which differences in Ig expression are affected.
机译：已经提出了精神分裂症的传染性和自身免疫性病原学假说，促使人们寻找针对病毒或脑结构的抗体，以及改变的免疫球蛋白水平。先前的实验表明，Ig重链3'增强子HS1,2 * A的等位基因频率与几种自身免疫性疾病有关，提示HS1,2等位基因与Ig产生之间可能存在相关性。为了测试这一点，我们分析了两个独立队列中的血清Igs和HS1,2 * A基因型水平，其中一个是88名精神分裂症住院患者（24名女性），另一名是133名健康受试者（59名女性）。两组患者血清Ig类和IgG亚类的浓度改变的频率相似（精神分裂症组为80％;对照组为68％）。除奥氮平具有稳定作用外，精神分裂症患者血清采样前一个月内没有服用任何心理药物会显着影响Ig水平。在患者和对照组中，HS1,2 * 2A等位基因频率的增加对应于Ig血浆水平的升高，而HS1,2 * 1A affele频率的增加对应于Ig血浆水平的降低。用人B细胞核提取物进行的EMSA分析表明，转录因子SP1与HS1,2 * 1A和HS1,2 * 2A的多态性区域结合，而NF-κB仅与HS1,2 * 2A结合。我们预测3'IgH增强子HS1,2的两个等位基因变体中转录因子结合位点的差异可能提供了一种机制，通过该机制可以影响Ig表达的差异。

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