HIGH DIAGNOSTIC-ACCURACY FOR IDIOPATHIC ADDISONS-DISEASE WITH A SENSITIVE RADIOBINDING ASSAY FOR AUTOANTIBODIES AGAINST RECOMBINANT HUMAN 21-HYDROXYLASE

Autoantibodies against 21-hydroxylase (P450c21) are common in idiopath ic autoimmune Addison's disease. In the present work, we have develope d a sensitive radiobinding assay using in vitro translated recombinant human S-35-P450c21. Levels of P450c21 antibodies (P450c21-Ab) were ex pressed as a relative index (P450c21 index) using a P450c21-Ab positiv e Addisonian serum and two antibody-negative healthy sera as positive and negative standards in healthy individuals. The upper level of norm al was the mean + 3 SD. Positivity for P450c21-Ab was confirmed by sod ium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) anal ysis of immunoprecipitated S-35-P450c21. In 38 Addisonian patients, P4 50c21-Ab were found in 24/28 (86%) idiopathic, 0/5 past-tuberculosis, 0/3 adrenoleukodystrophy, and 0/2 post-adrenalectomy sera. Among healt hy individuals, 1/70 (1.4%) were positive. The P450c21 index, as an es timate of P450c21-Ab levels, correlated inversely with the duration of idiopathic Addison's disease (r = -0.527; P = 0.007): 16/16 (100%) po sitive in patients with less than 20 yr and 8/12 (67%) positive in pat ients with more than 20 yr disease duration. The availability of this simple and sensitive radiobinding assay to evaluate levels of P450c21- Ab will permit large clinical studies as well as screening subjects at risk. In addition, the general population can now be screened to eval uate the predictive value of P450c21-Ab for Addison's disease.