Autoantibodies to adrenal cytochrome P450 antigens in isolated Addison's disease and autoimmune polyendocrine syndrome type II

Exp Clin Endocrinol Diabetes. 1999;107(3):208-13. doi: 10.1055/s-0029-1212100.


Adrenal P450 enzymes 21-hydroxylase (21OH), 17alpha-hydroxylase (17OH) 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 21OH (21OH-A) was observed in patients with isolated Addison's disease (IAD) and patients suffering from autoimmune polyendocrine syndrome type II (APS II). 21OH-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 17OH (17OH-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 17OH antibodies (n = 3) and SCC-A (n = 1), respectively (p < 0.0001). The majority of patients with 17OH-A (83.3%) or SCC-A (76.9%) were also found positive for 21OH-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 21OH-A, 17OH-A and SCC-A, respectively. By combination of 21OH-A with 17OH-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 17OH-A or SCC-A may suggest the coexistence of or progression towards polyglandular autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / blood
  • Addison Disease / immunology*
  • Adolescent
  • Adrenal Cortex / enzymology
  • Adrenal Cortex / immunology
  • Adrenal Glands / enzymology*
  • Adrenal Glands / immunology
  • Adult
  • Anemia, Pernicious / blood
  • Anemia, Pernicious / immunology
  • Autoantibodies / blood*
  • Child
  • Cholesterol Side-Chain Cleavage Enzyme / immunology
  • Cytochrome P-450 Enzyme System / immunology*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Male
  • Middle Aged
  • Polyendocrinopathies, Autoimmune / blood
  • Polyendocrinopathies, Autoimmune / immunology*
  • Reference Values
  • Steroid 17-alpha-Hydroxylase / immunology
  • Steroid 21-Hydroxylase / immunology
  • Syndrome
  • Thyroid Diseases / blood
  • Thyroid Diseases / immunology


  • Autoantibodies
  • Cytochrome P-450 Enzyme System
  • Steroid 21-Hydroxylase
  • Steroid 17-alpha-Hydroxylase
  • Cholesterol Side-Chain Cleavage Enzyme