Abstract
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.
Highlights
The frequencies and levels of antibodies against the seven microbial peptides are shown in Fig 1 and Table 3. 90.8% (69/76) of the anti-glomerular basement membrane (GBM) patients had circulating IgG against at least one peptide, and 82.9% (63/76) had IgM
The present study demonstrated that microbe-derived peptides with critical motif on α3(IV) NC1 could be recognized by the majority of anti-GBM patients
Their antibodies showed cross-reaction with those against P14 and α3(IV)NC1. These findings implicate that molecular mimicry might be a link between infection and autoimmunity in human anti-GBM disease
Summary
81330020, Mr Ming-hui Zhao; National Natural Science Foundation of China (CN) 81400703, Ms Xiaoyu Jia; Natural Science Fund of China to the Innovation Research Group 81621092, Mr Minghui Zhao; National Natural Science Fund of China 81370801, Mrs Zhao Cui; Natural Science Fund of China to the Outstanding Young Scholar 81622009, Mrs Zhao Cui; National Basic Research Program of China 2015CB910501, Mr Taijiao Jiang, Fundamental Research Funds for the Central Universities 2015RC310003, Mr Taijiao Jiang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
