Summary
Adrenal P450 enzymes 21-hydroxylase (21 OH), 17α -hydroxylase (170H) and side chain cleavage enzyme (SCC) represent major target antigens in adrenal autoimmunity. To evaluate the diagnostic sensitivity of autoantibodies to recombinant adrenal antigens we established rapid and sensitive radioligand assays and compared the results with adrenocortical autoantibodies (ACA) as detected by the standard immunofluorescence test. A high prevalence of antibodies to 21 OH (210H-A) was observed in patients with isolated Addison's disease (IAD) and patients suffering from autoimmune polyendocrine syndrome type II (APS II). 210H-A were found in 19 of 25 (76%) patients with IAD and in 34 of 40 (85%) patients with APS II. In contrast, antibodies to 170H (170H-A) as well as antibodies to SCC (SCC-A) were detected in 12 (30%) and 13 (33%) patients with APS II whereas only a few sera from patients with IAD had 170H antibodies (n = 3) and SCC-A (n = 1), respectively (p < 0.0001). The majority of patients with 170H-A (83.3%) or SCC-A (76.9%) were also found positive for 210H-A and all three antibody specificities were positively correlated with the presence of ACA. Among 52 sera with ACA 49 (94.2%), 11 (21.2%), and 9 (17.3%) were positive for 210H-A, 170H-A and SCC-A, respectively. By combination of 210H-A with 170H-A all ACA positive individuals were identified.
The availability of recombinant steroid P450 enzymes made it possible to develop radiobinding assays which allow simple, sensitive and quantitative detection of autoantibodies to defined adrenal autoantigens. We here demonstrate that autoantibodies to 21-hydroxylase are sensitive markers for autoimmune Addison's disease with and without polyglandular failure. The presence of 170H-A or SCC-A may suggest the coexistence of or progression towards polyglandular autoimmunity.
Key words
21-hydroxylase - 17α-hydroxylase - side chain cleavage enzyme - Addison's disease - autoimmune polyendocrine syndrome type II
