Plasma from patients with anti-glomerular basement membrane disease could recognize microbial peptides.
Plasma from patients with anti-glomerular basement membrane disease could recognize microbial peptides.
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抗肾小球基底膜疾病患者的血浆可以识别微生物肽
DOI：
10.1371/journal.pone.0174553
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhao MH
中科院分区：
文献类型：
--
作者：
Li JN;Jia X;Wang Y;Xie C;Jiang T;Cui Z;Zhao MH
长期以来，感染一直被怀疑是自身免疫性疾病的触发因素，本研究假设了分子模仿机制。根据α3129−150、异亮氨酸137、色氨酸140、甘氨酸142、苯丙氨酸143和苯丙氨酸145的关键氨基酸基序，从Uniprot数据库中检索微生物来源的肽。利用我们的搜索策略共鉴定出23826条微生物肽，其中7条与人类感染有关。采用ELISA法检测76例抗gbm患者血清中抗7种微生物肽的IgG和IgM抗体。4个肽段同时被IgG和IgM抗体识别，1个肽段仅被IgG抗体识别。在抗gbm患者中，拟杆菌、酿酒酵母菌和嗜热双歧杆菌的多肽的识别率最高，分别为IgG的73.7%、61.8%和67.1%，IgM的56.6%、44.7%和67.1%。具有这些微生物肽抗体的患者表现出更严重的肾损伤，包括较高的血清肌酐和较高的新月形成百分比。综上所述，在抗gbm患者的血液循环中发现了针对微生物肽的抗体，这意味着其病因学作用是通过分子模拟引发针对α3(IV)NC1的自身免疫反应。
Infection has long been suspected as a trigger of autoimmune diseases, and molecular mimicry mechanism was hypothesized in this study. Microbe originated peptides were searched from the Uniprot database based on a previous defined critical amino acid motif within α3129−150, isoleucine137, tryptophan140, glycine142, phenylalanine 143 and phenylalanine 145. 23826 microbial peptides were identified using our searching strategy, among which seven were related with human infections. Circulating IgG and IgM antibodies against the seven microbial peptides were detected using ELISA in 76 patients with anti-GBM disease. Four peptides were recognized by both IgG and IgM antibodies, and one peptide was recognized by IgG antibodies only. Peptides from Bacteroides, Saccharomyces cerevisiae, and Bifidobacterium thermophilum possessed the highest recognition frequency with the prevalence of 73.7%, 61.8% and 67.1% for IgG, 56.6%, 44.7% and 67.1% for IgM in anti-GBM patients. Patients with antibodies against these microbial peptides showed more severe kidney injury, including higher serum creatinine and higher percentage of crescent formation. In conclusion, antibodies against microbial peptides were identified in the circulation of anti-GBM patients, implying its etiological role in eliciting autoimmune response against α3(IV)NC1 through molecular mimicry.