Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis.
In our previous work, including analysis of more than 10,000 sera from control patients and patients with a variety of liver diseases, we have demonstrated that with the use of recombinant autoantigens, antimitochondrial autoantibodies (AMAs) are only found in primary biliary cirrhosis (PBC) and that a positive AMA is virtually pathognomonic of either PBC or future development of PBC. Although the mechanisms leading to the generation of AMA are enigmatic, we have postulated that xenobiotic-induced and/or oxidative modification of mitochondrial autoantigens is a critical step leading to loss of tolerance. This thesis suggests that a severe liver oxidant injury would lead to AMA production. We analyzed 217 serum samples from 69 patients with acute liver failure (ALF) collected up to 24 months post-ALF, compared with controls, for titer and reactivity with the E2 subunits of pyruvate dehydrogenase, branched chain 2-oxo-acid dehydrogenase, and 2-oxo-glutarate dehydrogenase. AMAs were detected in 28/69 (40.6%) ALF patients with reactivity found against all of the major mitochondrial autoantigens. In addition, and as further controls, sera were analyzed for autoantibodies to gp210, Sp100, centromere, chromatin, soluble liver antigen, tissue transglutaminase, and deaminated gliadin peptides; the most frequently detected nonmitochondrial autoantibody was against tissue transglutaminase (57.1% of ALF patients).


CONCLUSIONS
The strikingly high frequency of AMAs in ALF supports the thesis that oxidative stress-induced liver damage may lead to AMA induction. The rapid disappearance of AMAs in these patients provides further support for the contention that PBC pathogenesis requires additional factors, including genetic susceptibility.
Division of Rheumatology/Allergy, University of California, Davis Medical Center, Sacramento, CA, USA.
Patrick S C
PS
Leung
Lorenzo
L
Rossaro
Paul A
PA
Davis
Ogyi
O
Park
Atsushi
A
Tanaka
Kentaro
K
Kikuchi
Hiroshi
H
Miyakawa
Gary L
GL
Norman
William
W
Lee
M Eric
ME
Gershwin
D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015151:Immunoblotting; D008105:Liver Cirrhosis, Biliary / Q000453:epidemiology / Q000209:etiology / Q000276:immunology*; D017114:Liver Failure, Acute / Q000097:blood / Q000150:complications / Q000276:immunology*; D008297:Male; D008928:Mitochondria / Q000276:immunology*; D015995:Prevalence; D012737:Sex Factors; D013997:Time Factors
D001323:Autoantibodies