Autoantibodies against aromatic L-amino acid decarboxylase identifies a subgroup of patients with Addison's disease

Autoantibodies against aromatic L-amino acid decarboxylase (AADC) are prese nt in about 50 percent of sera from patients with autoimmune polyendocrine syndrome type I(APS I) but absent in sera from patients with different orga n-specific autoimmune diseases, such as insulin-dependent diabetes mellitus , Hashimoto's thyroiditis, and Graves' disease. AADC is expressed in the pa ncreatic P-cells, the liver, and the nervous system; and the presence of AA DC antibodies has been shown to correlate to hepatitis and vitiligo in APS I patients. Among 101 investigated patients with autoimmune Addison's disease, 15 had h igh titers of AADC antibodies. According to the clinical characteristics of these patients, only 3 had APS I. The remaining 12 had either isolated Add ison's disease or associated diabetes mellitus, hypothyroidism, vitiligo, a lopecia, gonadal failure, and pernicious anemia. Autoantibodies against 21- hydroxylase were present in 9 of 12, whereas autoantibodies against side-ch ain cleavage enzyme and 17 alpha-hydroxylase were present in 3 of 12. Two p atients had only autoantibodies against AADC. DNA was available from 3 of t hese 12 patients. One of the patients, a woman with Addison's disease, auto immune thyroiditis, and premature menopause was heterozygous for a point mu tation (G1021A, Val301Met) in the first plant homeodomain zinc finger domai n of the autoimmune regulator (AIRE) gene. The presence of AADC autoantibodies identifies patients with APS I and a su bgroup of Addison patients who may have a milder atypical form of APS I or represent a distinct entity. Measurement of autoantibodies against AADC sho uld be included in the evaluation of Addison's disease.