Characterization of anti-heart mitochondria autoantibodies produced in dogs following myocardial infarction.

A complement-fixing, heart-reactive serum component that develops in dogs following experimental myocardial infarction was characterized with respect to its immunoglobulin nature and its subcellular membrane and organ specificities. The immunoglobulin nature of the heart-reactive serum factor was established by the following evidence: (1) the factor was not removed from the serum following absorption of up to 90<7( of the first component of dog complement with bovine serum albumin (BSA)-anti-BSA immune precipitates, (2) the serum factor sedimented in the 19S region of sucrose density gradients, and (3) affinity chromatography using a Sepharose column coupled with rabbit anti-dog /x-chain-specific antibody resulted in the removal of nearly all of the heart-reactive substance. The major subcellular autoantigenic locus of the dog heart was determined to be the outer mitochondrial membrane. Serum containing the autoantibody demonstrated a six-fold greater autoantibody titer when outer mitochondrial membrane was used as the test antigen than it did when inner mitochondrial membrane was used. Absorption expei-iments suggested that the autoantigenic determinants residing on inner and outer mitochondrial membranes were unique to the individual membranes. Significant cross-reaction of the anti-heart autoantibody between heart and skeletal muscle mitochondria was observed, but no cross-reaction was seen with dog liver mitochondrial membranes.