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 present in about 50 percent of sera from patients with autoimmune polyendocrine syndrome type I (APS I) but absent in sera from patients with different organ-specific autoimmune diseases, such as insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and Graves' disease. AADC is expressed in the pancreatic beta-cells, the liver, and the nervous system; and the presence of AADC 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 high titers of AADC antibodies. According to the clinical characteristics of these patients, only 3 had APS I. The remaining 12 had either isolated Addison's disease or associated diabetes mellitus, hypothyroidism, vitiligo, alopecia, gonadal failure, and pernicious anemia. Autoantibodies against 21-hydroxylase were present in 9 of 12, whereas autoantibodies against side-chain cleavage enzyme and 17alpha-hydroxylase were present in 3 of 12. Two patients had only autoantibodies against AADC. DNA was available from 3 of these 12 patients. One of the patients, a woman with Addison's disease, autoimmune thyroiditis, and premature menopause was heterozygous for a point mutation (G1021A, Val301Met) in the first plant homeodomain zinc finger domain of the autoimmune regulator (AIRE) gene. The presence of AADC autoantibodies identifies patients with APS I and a subgroup of Addison patients who may have a milder atypical form of APS I or represent a distinct entity. Measurement of autoantibodies against AADC should be included in the evaluation of Addison's disease.
Söderbergh
A
A
Department of Clinical Sciences, University Hospital, Uppsala, Sweden. annika.soderbergh@medicin.uu.se
Rorsman
F
F
Halonen
M
M
Ekwall
O
O
Björses
P
P
Kämpe
O
O
Husebye
E S
ES
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000224:Addison Disease / Q000175:diagnosis* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism
D001323:Autoantibodies; D015415:Biomarkers; D015067:17-Hydroxysteroid Dehydrogenases; D013255:Steroid 21-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D001142:Aromatic-L-Amino-Acid Decarboxylases