Autoantibodies to specific enzymes: a review

There are two categories of autoantibodies to specific enzymes: immunoglobulin-complexed enzymes and circulating autoantibodies directed to enzymes in tissue or tissues. Immunoglobulin-complexed enzymes may result in elevated serum enzyme activity. They are found more frequently in elderly patients and have limited clinical significance. Immunoglobulin association with the enzyme must be demonstrated to distinguish this macroenzyme from other high molecular weight enzyme complexes. Autoantibodies to specific enzymes or regulators of enzyme activity do possess specific disease associations. The titers or presence of these autoantibodies may predict morbidity or response to therapy. These autoantibodies may be detected by Western blotting, enzyme-linked immunosorbent assays, tissue immunofluorescence, radioimmunoassay, immunoprecipitation flow cytometry or inhibition of enzyme activity. For example, anti-pyruvate dehydrogenase inhibits the activity of purified enzyme, but not relatively intact mitochondrial preparations. Most evidence suggests that the production of autoantibodies to specific enzymes represents an epiphenomenon secondary to tissue damage rather than a primary event in the pathogenetic pathway.