Epitope analysis of anti-myeloperoxidase antibodies in patients with ANCA-associated vasculitis

• Published in: PloS one Vol. 8; no. 4; p. e60530
• Main Authors: Gou, Shen-Ju, Xu, Peng-Cheng, Chen, Min, Zhao, Ming-Hui
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.04.2013; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino acid sequence; Analysis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - blood; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - pathology; Antibodies; Antibodies - blood; Antibodies - immunology; Antigenic determinants; Antigens; Antineutrophil cytoplasmic antibodies; Arthritis; Binding; Biology; Biopsy; Care and treatment; Chains; Creatinine; Cross Reactions; Disease prevention; E coli; Education; Enzyme-linked immunosorbent assay; Enzymes; Epitope Mapping; Epitopes; Female; Fragmentation; Fragments; Hospitals; Humans; Immunoglobulins; Immunology; Kidney diseases; Laboratories; Male; Medicine; Middle Aged; N-Terminus; Nephrology; Neutrophils; Patients; Peptide Fragments - immunology; Peroxidase; Peroxidase - genetics; Peroxidase - immunology; Peroxidase - isolation & purification; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - isolation & purification; Recurrence; Rheumatology; Sequence Deletion; Studies; Vasculitis; Young Adult; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060530

Increasing evidences have suggested the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCA) directing myeloperoxidase (MPO) in ANCA-associated vasculitis (AAV). The current study aimed to analyze the association between the linear epitopes of MPO-ANCA and clinicopathological features of patients with AAV. Six recombinant linear fragments, covering the whole length amino acid sequence of a single chain of MPO, were produced from E.coli. Sera from 77 patients with AAV were collected at presentation. 13 out of the 77 patients had co-existence of serum anti-GBM antibodies. Ten patients also had sequential sera during follow up. The epitope specificities were detected by enzyme-linked immunosorbent assay using the recombinant fragments as solid phase ligands. Sera from 45 of the 77 (58.4%) patients with AAV showed a positive reaction to one or more linear fragments of the MPO chain. The Birmingham Vasculitis Activity Scores and the sera creatinine were significantly higher in patients with positive binding to the light chain fragment than that in patients without the binding. The epitopes recognized by MPO-ANCA from patients with co-existence of serum anti-GBM antibodies were mainly located in the N-terminus of the heavy chain. In 5 out of the 6 patients, whose sera in relapse recognize linear fragments, the reactivity to linear fragments in relapse was similar to that of initial onset. The epitope specificities of MPO-ANCA were associated with disease activity and some clinicopathological features in patients with ANCA-associated vasculitis.