Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: Relationship of levels of autoantibodies to disease progression
✍ Scribed by Michael D. Van Norstrand; Michael Malinchoc; K. D. Lindor; T. M. Therneau; M. E. Gershwin; P. S. Leung; E. R. Dickson; H. A. Homburger
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 206 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
AMAs are detectable by indirect immunofluorescence (IF)
We examined the clinical usefulness of measurements on tissue substrates in 93% to 99% of patients with PBC, but of antimitochondrial autoantibodies (AMA) in prethis method also detects AMAs of differing specificities in dicting disease progression in patients with primary bilother diseases. The mitochondrial antigens recognized by iary cirrhosis (PBC). We determined the relationships AMAs in patients' sera have been classified numerically as between AMA levels measured by indirect immunofluo-M1 through M9, with the M2 antigen complex recognized by rescence (IF) and those measured by quantitative en-AMAs in sera from 95% to 99% of PBC patients. M2 antigen is zyme immunoassays (EIAs) using recombinant 2-oxocomposed of enzyme proteins of the 2-oxo-acid dehydrogenase acid dehydrogenase complex (2-OADC) proteins and the complex (2-OADC) family that are located on inner mitochon-Mayo Risk Score, an established indicator of disease prodrial membranes. Included in this group of autoantigens are gression in primary biliary cirrhosis (PBC). Results of tests for AMA by either method correlated weakly (r Å pyruvate dehydrogenase complex (PDC), branched-chain 2-.24 to .30) with disease progression as indicated by Mayo oxo-acid dehydrogenase complex (BCOADC), and 2-oxo-glu-Risk Scores. The levels of AMA to 2-OADC proteins vartarate dehydrogenase complex (OGDC). The 2-OADC enied by more than 200-fold between patients but rezymes are complex multimers composed of E1, E2, and E3 mained relatively constant over time in individual pasubunits; the E2 subunits contribute immunodominant epitients. Despite being positively correlated with Mayo topes recognized by anti-M2 autoantibodies. 3 Immunoreac-Risk Score results, the levels of AMA to 2-OADC proteins tive epitopes of the E2 subunits of 2-OADC enzymes have were not useful for predicting disease progression in been cloned, and enzyme immunoassays (EIAs) that use reindividual patients with PBC. In addition, we found no combinant PDC-E2 and BCOADC-E2 proteins as capture ansignificant differences in the levels of autoantibodies to tigens detect autoantibodies in sera from more than 95% of 2-OADC proteins among patients with different histologpatients with PBC. 4 Approximately 10% of sera from PBC ical stages of disease. Our results show that measurepatients contain autoantibodies to BCOADC-E2 but not PDCments of AMA by IF or by quantitative EIA methods with E2. Recently, Leung et al. 5 constructed a recombinant hybrid recombinant 2-OADC proteins are not useful parameters molecule that contains the immunodominant epitopes of both for predicting disease progression in patients with PBC. PDC-E2 and BCOADC-E2, and this hybrid molecule is recog-(HEPATOLOGY 1997;25:6-11.)
nized by AMAs specific for either antigen.
No study to date has reported on the levels of AMA to 2-OADC enzyme proteins in sera from a large number of PBC Primary biliary cirrhosis (PBC) is a progressive liver dispatients who have been followed up longitudinally throughease characterized by inflammatory destruction of intraheout the course of the disease. Consequently, the usefulness patic bile ducts. The pathogenic mechanisms of bile duct deof measurements of AMAs specific for 2-OADC proteins as struction in PBC are unknown, but it has been suggested that independent predictors of disease progression in patients autoantibodies to mitochondrial antigens that are present in with PBC is not documented. The Mayo Risk Score is an nearly all patients with PBC may play a role in the inflammaestablished, clinically useful predictor of the current risk of tory process. 1 This concept is supported indirectly by recent mortality in individual patients with PBC, and it has the data suggesting that the titers of antimitochondrial autoantiadvantage of using readily obtainable laboratory data (serum bodies (AMAs) correlate with histological progression of liver bilirubin concentration, serum albumin concentration, and damage in patients with PBC. 2 plasma prothrombin time) and physical findings (edema) without relying on the results of a liver biopsy. 6 However, the Mayo Risk Score does not include measurements of variables Abbreviations: PBC, primary biliary cirrhosis; AMA, antimitochondrial antibody; IF, which might be reflective of the pathogenesis of PBC.
indirect immunofluorescence; 2-OADC, 2-oxo-acid dehydrogenase complex; PDC, pyruvate
In this study, we examined the associations between AMA dehydrogenase complex; BCOADC, branched-chain 2-oxo-acid dehydrogenase complex; levels and disease progression in PBC. We measured AMAs OGDC, 2-oxo-glutarate dehydrogenase complex; EIA, enzyme immunoassay; Ig, immunoglobulin; bp, base pair; cDNA, complementary DNA; PBS, phosphate-buffered saline; CV, by two different methods, conventional IF on tissue substrate coefficient of variation.