Organ-specific and non-organ-specific autoantibodies in children and youngadults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy(APECED)

Objective: The aim of the study was to assess the complex of autoantibodies which can be detected in patients with autoimmune polyendocrinopathy-candi diasis-ectodermal dystrophy (APECED), a rare autosomal recessive disease in which the extent of autoimmunity is still unknown. Design: Antibodies (A) to parathyroid glands, adrenal cortex (AC-A), ovary and testis (steroid cell antibodies, SC-A), pancreatic islet cells (IC-A), gastric parietal cells, and non-organ-specific antigens were investigated i n 11 APECED patients living in the Salento region of southern Italy. Furthe r measurements included antibodies to cytochrome P450 (CYP) enzymes: choles terol side-chain cleavage enzyme (CYP11A), 21-hydroxylase (CYP21) and 17 al pha-hydroxylase (CYP17); and to glutamic acid decarboxylase 65-kDa isoform (GAD65), tyrosine phosphatase-like protein IA2, thyroglobulin (TG), thyrope roxidase (TPO), thyrotropin receptor, liver CYP enzymes and intrinsic facto r. Methods: Antibodies to organs and subcellular fractions were detected by im munofluorescence. Radiobinding, immunoradiometric, and immunoblotting assay s were used for the other measurements. Results: AC-A and SC-A were positive in all sera; among antibodies to adren al CYP enzymes, only CYP21-A were present in all the patients with Addison' s disease of short-medium duration (<15 years). Of three patients with Addi son's disease of long duration (>15 years), two tested positive for antibod ies to all three CYP enzymes, and the other for only CYP11A-A. In all sera CYP11A-A and/or CYP17-A were found. Two patients tested positive for both I C-A and GAD65-A, one for both IC-A and IA2-A, and one for GAD65-A: the fast ing C-peptide assay showed no statistical difference between these four sub jects and the others. All four hypothyroid patients were positive for TPO-A , while two of them were positive and two were negative for TG-A; two euthy roid subjects had positivity for TG-A. Liver-kidney microsomal antibodies r eacting against the CYP2A6 were detected in two patients with autoimmune he patitis. All but one sera contained anti-nuclear antibodies at a titre rang ing between 1:20 and 1:80; however only two patients had a connective tissu e disease (Sjogren's syndrome). Conclusions: Several autoantibodies may be detected in any APECED patient. Our data confirm that CYP21-A and TPO-A are major autoantibodies involved i n APECED-associated Addison's disease and hypothyroidism respectively, whil e CYP11A-A and CYP17-A correlate with positivity for SC-A. Markers of islet cell autoimmunity are frequent. but prevalence and modalities of progressi on to overt P-cell failure have to be clarified. Low-titre non-organ-specif ic autoantibodies are a feature of autoimmunity in APECED, but their role h as yet to be fully explained.