Demonstration of "naturally occurring mitochondrial antibodies" in family members of patients with primary biliary cirrhosis.

Sera from 81 healthy family members (including husbands) of 13 patients with primary biliary cirrhosis were tested by Western blotting against the antigen fractions M9 and M2 derived respectively from rat liver and beef heart mitochondria. Fifty-eight (70%) were positive and recognized four major (molecular weights 98 kD, 65 kD, 61 kD, 58 kD) and eight minor determinants (85 kD, 81 kD, 78 kD, 54 kD, 48 kD, 45 kD, 40 kD, 30 kD) labeled alpha-my. Each of the 58 sera recognized at least one of the four major polypeptides. In contrast, only 6% of 80 primary biliary cirrhosis patients had antibodies against one of these epitopes. Sera from 25 patients with different infectious disorders previously shown to react with submitochondrial particles by enzyme-linked immunosorbent assay also recognized at least one of the four major determinants. From these findings it was concluded that these antibodies may belong to the family of natural autoantibodies. Since they reacted with submitochondrial fractions, they were defined as "naturally occurring mitochondrial antibodies". The high incidence of "naturally occurring mitochondrial antibodies" in primary biliary cirrhosis-contact persons may be taken as indirect evidence for a contagious immunogenic agent circulating in the blood of primary biliary cirrhosis-patients. In contrast, the absence of "naturally occurring mitochondrial antibodies" in primary biliary cirrhosis-patients themselves implies that an underlying B-cell defect is responsible for this lack of antibody production. Considering the protective role of naturally occurring antibodies in general, this postulated B-cell defect could be a major factor in the etiopathogenesis of primary biliary cirrhosis.