Mycoplasma antigens as a possible trigger for the induction of antimitochondrial antibodies in primary biliary cirrhosis.
BACKGROUND
In primary biliary cirrhosis (PBC), autoreactivity mainly targets members of the pyruvate dehydrogenase complex (PDC). Because PDC subunits are expressed on the surface of mycoplasma and molecular mimicry may be one aetiological factor, we analysed the presence of mammalian and mycoplasma PDC-specific antibodies in PBC patients.


METHODS
Antibodies to porcine PDC and Mycoplasma pneumoniae (mp) antigens mpPDH-C (to be designated mpPDC-E2 chain), mpPDH-B (to be designated mpPDC-E1beta chain), mpCARDS TX and mpP1 were investigated in sera from 43 PBC patients, 19 patients with autoimmune hepatitis and 11 healthy controls by an enzyme-linked immunosorbent assay and Western blotting. To study the rate of acute mycoplasma infection, an adhesin P1-specific polymerase chain reaction (PCR) was performed.


RESULTS
Immune reactivity to the mpPDC-E2 antigen was significantly enhanced in PBC patients (83.7%) as compared with controls (overall frequency of 36.7%), while antibodies to the porcine PDC-E2 chain were found only in PBC patients (88%) excluding a simple cross-reactivity of PDC-related antibodies. This observation was confirmed by inhibition studies demonstrating that porcine PDC did not inhibit mycoplasma PDC-specific antibodies and vice versa. The occurrence of antibodies to mpPDC seems to precede the occurrence of antibodies to porcine PDC. Infection with mycoplasma was equally distributed in the groups as evidenced by an antibody frequency comparable to CARDS TX and P1 and PCR reactivity.


CONCLUSIONS
Because PBC patients show a significantly enhanced frequency of mpPDC-E2-related antibodies, besides other factors, molecular mimicry between surface molecules of mycoplasma and epitopes of the autoantigen may play a central role in the aetiopathology of PBC.
Berg
Christoph P
CP
Department of Internal Medicine I, Medical Clinic, Eberhard-Karls-University of Tübingen, Tübingen, Germany.
Kannan
Thirumalai R
TR
Klein
Reinhild
R
Gregor
Michael
M
Baseman
Joel B
JB
Wesselborg
Sebastian
S
Lauber
Kirsten
K
Stein
Gerburg M
GM
D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000097:blood; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005858:Germany; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000276:immunology / Q000378:metabolism*; D018716:Molecular Mimicry / Q000502:physiology*; D009174:Mycoplasma / Q000276:immunology / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology / Q000378:metabolism*; D017634:Self Tolerance / Q000502:physiology*; D034421:Sus scrofa
D000906:Antibodies; D017931:DNA Primers; D024101:Mitochondrial Proteins; D011768:Pyruvate Dehydrogenase Complex