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

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          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 α3 129−150, 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.

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          Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein

          Structural similarity between viral T cell epitopes and self-peptides could lead to the induction of an autoaggressive T cell response. Based on the structural requirements for both MHC class 11 binding and TCR recognition of an immunodominant myelin basic protein (MBP) peptide, criteria for a data base search were developed in which the degeneracy of amino acid side chains required for MHC class 11 binding and the conservation of those required for T cell activation were considered. A panel of 129 peptides that matched the molecular mimicry motif was tested on seven MBP-specific T cell clones from multiple sclerosis patients. Seven viral and one bacterial peptide efficiently activated three of these clones. Only one peptide could have been identified as a molecular mimic by sequence alignment. The observation that a single T cell receptor can recognize quite distinct but structurally related peptides from multiple pathogens has important implications for understanding the pathogenesis of autoimmunity.
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            Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis.

            To examine possible risk factors for relapse, including chronic nasal carriage of Staphylococcus aureus and serial antineutrophil cytoplasmic antibody (ANCA) determinations in patients with Wegener granulomatosis. Observational cohort study. Outpatient clinic at a university-affiliated hospital. Consecutive patients (n = 71) with biopsy-proven Wegener granulomatosis who were seen during follow-up at the outpatient clinic from January 1988 to July 1991. Fourteen patients were ineligible or dropped out; 57 patients were analyzed. Serial ANCA determinations and swab cultures of both anterior nares for S. aureus taken at each visit every 4 to 6 weeks. Occurrence of infections and relapses of Wegener granulomatosis were identified according to strict, predefined criteria. Thirty-six of the 57 patients (63%; 95% CI, 49% to 76%) were found to be chronic nasal carriers of S. aureus (> or = 75% of nasal cultures positive for S. aureus). Proportional-hazards regression analysis identified chronic nasal carriage of S. aureus (adjusted relative risk, 7.16; CI, 1.63 to 31.50), creatinine clearance above 60 mL.min-1 (adjusted relative risk, 2.94; CI, 1.27 to 6.67), and a history of previous relapses of Wegener granulomatosis (adjusted relative risk, 1.33; CI, 0.98 to 1.78) as independent risk factors for relapse. Twenty-two of 33 patients persistently or intermittently positive for ANCA had a relapse as opposed to only 1 of 21 persistently negative patients. Relapses of Wegener granulomatosis were not related to diagnosed infections. Chronic nasal carriage of S. aureus identifies a subgroup of patients with Wegener granulomatosis who are more prone to relapses of the disease, suggesting a role for S. aureus in its pathophysiology and a possible clue for treatment.
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              Molecular mimicry and autoimmune disease.

              M Oldstone (1987)
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 April 2017
                2017
                : 12
                : 4
                : e0174553
                Affiliations
                [1 ]Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
                [2 ]Institute of Nephrology, Peking University, Beijing, China
                [3 ]Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
                [4 ]Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China
                [5 ]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
                [6 ]State Key Laboratory of Membrane Biology, Laboratory of Molecular Biophysics, School of Life Sciences, Peking University, Beijing, China
                [7 ]Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                [8 ]Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China
                [9 ]Peking-Tsinghua Center for Life Sciences, Beijing, China
                Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, MEXICO
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MZ.

                • Data curation: JL.

                • Formal analysis: JL.

                • Funding acquisition: ZC MZ TJ CX.

                • Investigation: JL.

                • Methodology: JL XJ YW.

                • Project administration: JL.

                • Resources: ZC TJ YW.

                • Software: JL YW.

                • Supervision: ZC MZ TJ.

                • Validation: ZC.

                • Visualization: JL ZC MZ.

                • Writing – original draft: JL.

                • Writing – review & editing: JL ZC MZ.

                Article
                PONE-D-16-39818
                10.1371/journal.pone.0174553
                5391914
                28410377
                130013f0-60d5-446e-a317-25d646492603
                © 2017 Li et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 October 2016
                : 10 March 2017
                Page count
                Figures: 3, Tables: 4, Pages: 14
                Funding
                Funded by: National Natural Science Foundation of China (CN)
                Award ID: 81330020,
                Award Recipient :
                Funded by: National Natural Science Foundation of China (CN)
                Award ID: 81400703
                Award Recipient :
                Funded by: Natural Science Fund of China to the Innovation Research Group
                Award ID: 81621092
                Award Recipient :
                Funded by: National Natural Science Fund of China
                Award ID: 81370801
                Award Recipient :
                Funded by: Natural Science Fund of China to the Outstanding Young Scholar
                Award ID: 81622009
                Award Recipient :
                Funded by: National Basic Research Program of China
                Award ID: 2015CB910501
                Award Recipient :
                Funded by: Fundamental Research Funds for the Central Universities
                Award ID: 2015RC310003
                Award Recipient :
                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.
                Categories
                Research Article
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antibodies
                Autoantibodies
                Medicine and Health Sciences
                Physiology
                Immune Physiology
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                Biology and Life Sciences
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                Chemical Synthesis
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                Custom metadata
                Ethical restrictions on data sharing have been imposed by the Ethics Committee of Peking University First Hospital to protect confidential patient information. To request access to these data, please contact the chair of this committee, Professor Yining Huang ( ynhuang1@ 123456126.com ) and Hong Zhang ( hongzh@ 123456bjmu.edu.cn ).

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