Disease-specific cross-reactivity between mimicking peptides of heat shock protein of Mycobacterium gordonae and dominant epitope of E2 subunit of pyruvate dehydrogenase is common in Spanish but not British patients with primary biliary cirrhosis.
Previous studies on Spanish patients with Primary Biliary Cirrhosis (PBC) have shown extensive, disease-specific cross-reactivity between the 65-kDa heat shock protein (hsp65) of Mycobacterium gordonae and pyruvate dehydrogenase complex-E2 (PDC-E2), the major target of anti-mitochondrial antibody (AMA). Studies on a British population were unable to substantiate these findings. Having found that there is an excellent and almost unique match between the PDC-E2 autoepitope and a sequence in mycobacterial hsp65s, we tested the corresponding peptides by ELISA for cross-reactivity using sera from 90 PBC patients, 40 Spanish and 50 British, and 84 pathological controls. Reactivity to the MYCGO hsp65(90-104)/human PDC-E2(212-226)pair was present in 19 (47.5%) Spanish PBC patients and in 2 (4%) of the 50 British. Reactivity was not seen in any of the controls. Simultaneous reactivity to mimics was due to cross-reactivity as confirmed by inhibition studies. Three dimensional modelling predicts mycobacterial hsp65(90-104)to be exposed on the surface of the protein. The affinity of anti-hsp65(90-104)antibody was higher than that of anti-PDC-E2(212-226). Hsp65(90-104)is a target of disease-specific cross-reactivity to PDC-E2(212-226). The geographical confinement of this phenomenon is probably the result of complex genetic, environmental and immunological interaction.
Bogdanos
Dimitrios-Petrou
DP
Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
Pares
Albert
A
Baum
Harold
H
Caballeria
Llorenc
L
Rigopoulou
Eirini I
EI
Ma
Yun
Y
Burroughs
Andrew K
AK
Rodes
Juan
J
Vergani
Diego
D
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000235:genetics; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009170:Nontuberculous Mycobacteria / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics / Q000276:immunology*; D013030:Spain; D006113:United Kingdom
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001323:Autoantibodies; D001324:Autoantigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D011768:Pyruvate Dehydrogenase Complex; C074119:heat-shock protein 65, Mycobacterium; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D018833:Chaperonins