Organ-specific and non-organ-specific autoantibodies in children and young adults 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-candidiasis-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 in 11 APECED patients living in the Salento region of southern Italy. Further measurements included antibodies to cytochrome P450 (CYP) enzymes: cholesterol side-chain cleavage enzyme (CYP11A), 21-hydroxylase (CYP21) and 17alpha-hydroxylase (CYP17); and to glutamic acid decarboxylase 65-kDa isoform (GAD65), tyrosine phosphatase-like protein IA2, thyroglobulin (TG), thyroperoxidase (TPO), thyrotropin receptor, liver CYP enzymes and intrinsic factor.

METHODS

Antibodies to organs and subcellular fractions were detected by immunofluorescence. Radiobinding, immunoradiometric, and immunoblotting assays were used for the other measurements.

RESULTS

AC-A and SC-A were positive in all sera; among antibodies to adrenal 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 Addison's disease of long duration (>15 years), two tested positive for antibodies 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 IC-A and GAD65-A, one for both IC-A and IA2-A, and one for GAD65-A; the fasting C-peptide assay showed no statistical difference between these four subjects 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 euthyroid subjects had positivity for TG-A. Liver-kidney microsomal antibodies reacting against the CYP2A6 were detected in two patients with autoimmune hepatitis. All but one sera contained anti-nuclear antibodies at a titre ranging between 1:20 and 1:80; however, only two patients had a connective tissue disease (Sjögren'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 in APECED-associated Addison's disease and hypothyroidism respectively, while CYP11A-A and CYP17-A correlate with positivity for SC-A. Markers of islet cell autoimmunity are frequent, but prevalence and modalities of progression to overt beta-cell failure have to be clarified. Low-titre non-organ-specific autoantibodies are a feature of autoimmunity in APECED, but their role has yet to be fully explained.