Antibodies against homologous microbial caseinolytic proteases P characterise primary biliary cirrhosis

被引:62
作者
Bogdanos, DP
Baum, H
Sharma, UC
Grasso, A
Ma, Y
Burroughs, AK
Vergani, D
机构
[1] UCL, Sch Med & Hosp, Inst Hepatol, Immunol Grp, London WC1E 6HX, England
[2] Kings Coll London, Div Life Sci, London WC2R 2LS, England
[3] Royal Free Hosp, Liver Transplantat & Hepatobilliary Med, London NW3 2QG, England
关键词
autoimmunity; cross-reactivity; infection; mimicry;
D O I
10.1016/S0168-8278(01)00252-5
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Antibodies to caseinolytic protease P(177-194) (ClpP(177-194)) of the proteolytic subunit of the Clp complex of Escherichia coli (E. coli) are uniquely present in primary biliary cirrhosis (PBC). Molecular mimicry between the regulatory subunit ClpX and the principal T-cell epitope of pyruvate dehydrogenase complex ( PDC-E2) in PBC, has been proposed to account for this. Since ClpP is highly conserved among bacteria we investigated whether the micro-organisms triggering these antibodies may be other than E. coli. Methods/Results: E. Coli ClpP(177-194) is homologous with ClpP peptides of Yersinia enterocolitica (YEREN) and Haemophilus influenzae (HAEIN). Enzyme linked immunosorbent assay (ELISA) reactivity to these peptides was tested in 45 patients with PBC, 44 pathological and 32 healthy controls. Reactivity to at least one of the ClpP peptides was observed in 21 (47%) PBC patients, 5.8% pathological and 3.1% healthy controls (P < 0.01 for all). Among these 21 seropositive PBC patients, 15 (71%) reacted to ECOLI ClpP(177-194), alone or in association with YEREN and/or HAEIN peptides, compared to three (14.2%) reactive with YEREN, two (9.5%) with YEREN/HAEIN and one (4.7%) with HAEIN peptide. Simultaneous reactivity to homologous sequences was due to cross-reactivity as confirmed by competition ELISAs. Conclusions: The PBC-specificity of anti-microbial ClpP reactivity is confirmed: the questions as to primary trigger(s) and relevance to PBC pathogenesis remain open. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.
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页码:14 / 21
页数:8
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