Epitope analysis of anti-myeloperoxidase antibodies in propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitisReport as inadecuate




Epitope analysis of anti-myeloperoxidase antibodies in propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitis - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 15:R196

First Online: 20 November 2013Received: 29 March 2013Accepted: 12 November 2013

Abstract

IntroductionIncreasing evidence has suggested that linear epitopes of antineutrophil cytoplasmic antibody ANCA directed to myeloperoxidase MPO might provide clues to the pathogenesis of propylthiouracil PTU-induced ANCA-associated vasculitis AAV. This study mapped epitopes of MPO-ANCA in sera from patients with PTU-induced MPO-ANCA with or without vasculitis and primary AAV, aiming to analyze certain epitopes associated with the development of PTU-induced AAV.

MethodsSix recombinant linear fragments, covering the whole amino acid sequence of a single chain of MPO, were produced from Escherichia coli. Sera from 17 patients with PTU-induced AAV, 17 patients with PTU-induced MPO-ANCA but without clinical evidence of vasculitis, and 64 patients with primary AAV were collected at presentation. Of the 17 patients with PTU-induced AAV, 12 also had sera at remission. The epitope specificities were detected by enzyme-linked immunosorbent assay by using the recombinant fragments as solid-phase ligands.

ResultsCompared with patients with PTU-induced MPO-ANCA but without clinical vasculitis, sera from PTU-induced AAV patients showed significantly higher reactivity against the H1 fragment of MPO optical density values: 0.17 0.10 to 0.35 versus 0.10 0.04 to 0.21, P = 0.038 and could recognize a significantly higher number of fragments two none to four versus one none to two, P = 0.026. Compared with sera from primary AAV patients, sera from PTU-induced AAV patients had significantly higher reactivity to the P fragment and the H4 fragment 47.1% versus 14.1% P < 0.001; 41.2% versus 14.1%, P = 0.034, respectively, and could recognize a significantly higher number of fragments two none to four versus one none to two, P = 0.013. Among the 12 PTU-induced AAV patients with sequential samples, the number of fragments recognized in remission was significantly less than that in initial onset two none to four versus none none to 0.75, P < 0.001.

ConclusionsLinear epitopes of MPO molecules might be associated closely with PTU-induced AAV. In particular, the P and H4 fragments may be important epitopes in PTU-induced AAV.

AbbreviationsAAVANCA-associated vasculitis

AECAAnti-endothelial cell antibodies

ANCAAntineutrophil cytoplasmic antibody

BPIBactericidal-permeability-increasing protein

BVASBirmingham Vasculitis Activity Score

EGPAEosinophilic granulomatosis with polyangiitis

GPAGranulomatosis with polyangiitis

HLEHuman leukocyte elastase

MPAMicroscopic polyangiitis

MPOMyeloperoxidase

PR3proteinase 3

PTUPropylthiouracil.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4386 contains supplementary material, which is available to authorized users.

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Author: Chen Wang - Shen-ju Gou - Peng-cheng Xu - Ming-hui Zhao - Min Chen

Source: https://link.springer.com/







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