Human muscle carbonic anhydrase III (CA-III). Purification, immunohistochemical localization in the human skeletal muscle and its clinical application to the neuromuscular disease.

The aim of the present work was to investigate histological localization of newly found human muscle CA-III and its diagnostic value in neuromuscular diseases. The following results were obtained. CA-III was purified as a single band from human skeletal muscle nd specific anti-CA-III antiserum was raised in the rabbits. By the direct immunoperoxidase method in human biceps muscle, CA-III was localized mainly in Type I fibers (red muscle type). A radioimmunoassay was developed for CA-III which can detect 5 ng/ml of sample. Among several human tissues, CA-III was found virtually specific to the skeletal muscles with a level of 5 mg/gm wet tissue. Normal serum CA-III level (n = 20) was 22.5 +/- 15.3 (SD) ng/ml. Among 140 cases of various diseases, elevated serum CA-III levels were found in 29 cases, all of which were only from neuromuscular diseases including 17 various muscular dystrophies, 5 polymyositis, 2 other myopathies and 5 ALS. In acute myocardial infarction with highly elevated CPK, serum CA-III remained normal. In 60 cases of various neuromuscular diseases, serum CA-III, CPK and aldolase were measured. Order of sensitivity (% frequency of elevated serum level) was CPK greater than CA-III greater than aldolase, however, CA-III was most frequently elevated in myotonic dystrophy which predominantly affects Type I fibers. In 15 ALS, raised CA-III was found in 5 cases, which were all in relatively early stages showing rapidly progressive clinical courses. This result raises a possibility to use serum CA-III for evaluation of the prognosis in ALS. It is concluded that CA-III is clinically applicable as a new diagnostic marker for muscle diseases, and probably reflects Type-I fiber abnormalities more sensitively than CPK and aldolase.