There are two categories of autoantibodies to specific enzymes: immuno
globulin-complexed enzymes and circulating autoantibodies directed to
enzymes in tissue or tissues. Immunoglobulin-complexed enzymes may res
ult in elevated serum enzyme activity. They are found more frequently
in elderly patients and have limited clinical significance. Immunoglob
ulin association with the enzyme must be demonstrated to distinguish t
his macroenzyme from other high molecular weight enzyme complexes. Aut
oantibodies to specific enzymes or regulators of enzyme activity do po
ssess specific disease associations. The titers or presence of these a
utoantibodies may predict morbidity or response to therapy. These auto
antibodies may be detected by Western blotting, enzyme-linked immunoso
rbent assays, tissue immunofluorescence, radioimmunoassay, immunopreci
pitation 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 s
uggests that the production of autoantibodies to specific enzymes repr
esents an epiphenomenon secondary to tissue damage rather than a prima
ry event in the pathogenetic pathway.