Autoantibodies to M2 mitochondrial autoantigens in normal human sera by immunofluorescence and novel assays

Abstract

Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (anti-M2), directed against the E2 subunits of the 2-oxo-acid dehydrogenase complexes (2-OADC), chiefly pyruvate dehydrogenase complex (PDC-E2). We present here a detailed study, based on a large panel of normal sera, of the specificity of tests for anti-M2 by immunofluorescence and for anti-PDC by other assays for the diagnosis of PBC. The assays for anti-PDC included immunoblotting with bovine heart mitochondria, ELISA using recombinant PDC-E2 and an enzyme inhibition assay using purified porcine PDC. The positivity rates for normal sera were 0 (0/170), 2 (4/201), 1.5 (3/198) and 0% (0/186) for immunofluorescence, immunoblotting, ELISA and the enzyme inhibition assay, respectively. The seven positive reactions detected either by immunoblotting (n = 4) or ELISA (n = 3) were negative by the other three assays and in no instance did biochemical indices give any indication of chronic liver disease. Thus, as judged by reactivity with normal sera, the specificity of a positive test for the antibody to the major M2 autoantigen (PDC-E2) is 100% for immunofluorescence and the enzyme inhibition assay, 98% for immunoblotting and 98.5% for ELISA.

Large‐scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis

“…(17)(18)(19) Systematic screening of blood donors and healthy subjects shows AMA-positive results in 0.07%-9.9% of individuals, depending on the techniques and diagnostic thresholds used, as well as on the type, age, and sex structures of the populations screened. (20)(21)(22)(23)(24) The relatively high rate (2.5% of all tests) of AMA positivity observed in our study may be related to the equivocal nature of low titers of AMAs detected by IF, but is more likely to be driven by the population concerned. The proportion of positive results is typically bigger in the female population above 40 years.…”

Prevalence of antimitochondrial antibody in Japanese corporate workers in Kanagawa prefecture

“…We believe that our sample does not represent a true general population, but it is closer to a general population than those examined in previous studies. [17][18][19][20] Mattalia et al 17 and Turchany et al 18 reported that most AMA-positive persons had normal liver function. Mattalia et al 17 detected AMA in 9 (0.5%) in a sample of 1530; all AMA-positive persons had normal liver function.…”

“…[17][18][19][20] Some of these previ- ous studies used an unacceptably large number of blood donors as study subjects, 17,19 or female-dominant samples, 17,19,20 or did not describe the age distribution, 17,19 or the sex ratio of the sample. 19 Blood donors have a self-selection bias, with subjects tending to be younger and healthier. One study selected a too-young sample, with a mean age of 31.7-years.…”

“…16 However, the prevalence of AMA in the general population is reported to range from 0.07% to 9.9%, accounting for 700 to 99 000 per million. [17][18][19][20] This difference between the prevalence of PBC and that of AMA stimulated us to undertake the research presented here.…”

Is anti-pyruvate dehydrogenase complex a predictor of the development of primary biliary cirrhosis?

“…[8][9][10][11][12][13] These studies raised the important question of whether AMA-positive healthy individuals would eventually develop PBC.…”