Plasma from patients with anti-glomerular basement membrane disease could recognize microbial peptides

PLoS One. 2017 Apr 14;12(4):e0174553. doi: 10.1371/journal.pone.0174553. eCollection 2017.

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.

MeSH terms

  • Acute Kidney Injury / pathology
  • Adult
  • Amino Acid Sequence
  • Anti-Glomerular Basement Membrane Disease / blood*
  • Anti-Glomerular Basement Membrane Disease / pathology
  • Antibodies, Antineutrophil Cytoplasmic / blood
  • Antibodies, Antineutrophil Cytoplasmic / immunology
  • Bacteroides / metabolism*
  • Bifidobacterium / metabolism*
  • Creatinine / blood
  • Databases, Protein
  • Female
  • Genotype
  • HLA-DRB1 Chains / genetics
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Male
  • Middle Aged
  • Peptides / chemistry
  • Peptides / immunology*
  • Saccharomyces cerevisiae / metabolism*
  • Severity of Illness Index
  • Vasculitis / etiology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • HLA-DRB1 Chains
  • HLA-DRB1*11 antigen
  • Immunoglobulin G
  • Immunoglobulin M
  • Peptides
  • Creatinine

Grants and funding

This work was supported by National Natural Science Foundation of China (CN) 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. Ming-hui 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.