Epitopes described in "Epitope specificity of myeloperoxidase antibodies: identification of candidate human immunodominant epitopes."

Reference
Article Authors:B F Bruner; E S Vista; D M Wynn; J A James
Article Title:Epitope specificity of myeloperoxidase antibodies: identification of candidate human immunodominant epitopes.
Reference Detail
Reference ID:1022148
Abstract:Anti-neutrophil cytoplasmic autoantibodies (ANCA) are a common feature of systemic vasculitides and have been classified as autoimmune conditions based, in part, on these autoantibodies. ANCA are subdivided further based on their primary target: cytoplasm (c-ANCA) or perinuclear region (p-ANCA). p-ANCAs commonly target myeloperoxidase (MPO), an enzyme with microbicidal and degradative activity. MPO antibodies are non-specific for any single disease and found in a variety of vasculitides, most commonly microscopic polyangiitis. Despite their prevalence, their role in human disease pathogenesis remains undefined. We sought to characterize the sequential antigenic determinants of MPO in vasculitis patients with p-ANCA. Of 68 patients with significant levels of p-ANCA, 12 have significant levels of MPO antibodies and were selected for fine specificity epitope mapping. Sequential antigenic targets, including those containing amino acids (aa) 213-222 (WTPGVKRNGF) and aa 511-522 (RLDNRYQPMEPN), were commonly targeted with a prevalence ranging from 33% to 58%. Subsequent analysis of autoantibody binding to the RLDNRYQPMEPN peptide was assessed using a confirmatory enzyme-linked immunosorbent assay format, with six patients displaying significant binding using this method. Antibodies against this epitope, along with four others (aa 393-402, aa 437-446, aa 479-488 and aa 717-726), were reactive to the heavy chain structure of the MPO protein. One epitope, GSASPMELLS (aa 91-100), was within the pro-peptide structure of MPO. B cell epitope prediction algorithms identified all or part of the seven epitopes defined. These results provide major common human anti-MPO immunodominant antigenic targets which can be used to examine further the potential pathogenic mechanisms for these autoantibodies.
Date:2011
Reference Type:Literature
PubMed ID:21401576
Journal:Clin Exp Immunol
Journal Volume:164
Article Pages:330-6
Journal ISSN:1365-2249
Article Chemical List:Autoantibodies;Epitopes;Immunodominant Epitopes;Peptide Fragments;Peroxidase
Article MeSH List:Aged; Algorithms; Antibody Affinity; Autoantibodies(immunology); Epitope Mapping; Epitopes; Female; Humans; Immunodominant Epitopes(metabolism); Male; Middle Aged; Peptide Fragments(immunology; metabolism); Peroxidase(immunology; metabolism); Protein Binding; Vasculitis(diagnosis; immunology)
Curation Last Updated:2014-04-01 21:11:30