Assessment of autoantibodies is a valuable tool in the diagnostic procedure of autoimmune diseases. The aim of this study was to investigate the prevalence of different autoantibodies and their associations with disease manifestations in patients with Addison's disease and autoimmune polyendocrine syndrome type I (APS I).

Sera from 89 of 101 patients with Addison's disease identified 21-hydroxylase (21-OH) in Western blot and/or in an immunoprecipitation assay. A minority of the patients also had autoantibodies against 17α-hydroxylase and side-chain cleavage enzyme (SCC). A subgroup of 12 patients had high titers of autoantibodies against the APS I-specific autoantigen aromatic L-amino acid decarboxylase (AADC), but lacked other characteristics of APS I, implying a milder atypical form of APS I, or perhaps a distinct disease entity in these patients.

Patients with APS I develop various autoantibodies against intracellular organ-specific key enzymes. Sera from 90 patients with APS I were investigated and in a multivariate logistic regression analysis autoantibodies against 21-OH, SCC, protein tyrosine phosphatase IA-2 (IA-2), tryptophan hydroxylase and glutamic acid decarboxylase 65 (GAD65) were found to be independent predictors for Addison's disease, hypogonadism, insulin-dependent diabetes mellitus, autoimmune hepatitis and intestinal dysfunction.

Down syndrome is associated with an increased incidence of organ-specific autoimmune diseases. The AIRE gene, located on chromosome 21, is mutated in patients with APS I. In an attempt to determine whether a gene-dose effect could contribute to autoimmunity in Down syndrome, sera from 48 patients were investigated. Seven patients had significant autoantibody titers against AADC, cytochrome P4501A2, GAD65, IA-2, or 21-OH. None of the patients had the associated disease manifestation. The presence of APS I-specific autoantibodies in patients with Down syndrome may be partly due to a dysregulation of the AIRE gene.