Antibodies against homologous microbial caseinolytic proteases P characterise primary biliary cirrhosis.
OBJECTIVE
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.


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.
Bogdanos
Dimitrios-Petrou
DP
Immunology Group, Institute of Hepatology, University College London Medical School and Hospitals, Harold Samuel House, 69-75 Chenies Mews, London WC1E 6HX, UK.
Baum
Harold
H
Sharma
Umesh C
UC
Grasso
Alessandro
A
Ma
Yun
Y
Burroughs
Andrew K
AK
Vergani
Diego
D
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000368:Aged; D003429:Cross Reactions; D049071:Endopeptidase Clp; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000201:enzymology / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology*
D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases