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- Söderbergh, Annika
(author)
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Organ-specific autoantibodies in Addison's disease and autoimmune polyendocrine syndrome type I
- 2000
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 2. |
- Söderbergh, Annika, et al.
(author)
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Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I
- 2004
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:2, s. 557-562
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Journal article (peer-reviewed)abstract
- The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17 alpha-hydroxylase, glutamic acid decarboxylase 65, aromatic L-amino acid decarboxylase, tyrosine phosphatase-like protein IA-2, tryptophan hydroxylase (TPH), tyrosine hydroxylase, cytochrome P450 1A2, and against the extracellular calcium-sensing receptor, was assessed in 90 patients with autoimmune polyendocrine syndrome type I. A multivariate logistic regression analysis was performed for the presence of autoantibodies as independent predictors for different disease manifestations. Reactivities against 21-hydroxylase and SCC were associated with Addison's disease with odds ratios (ORs) of 7.8 and 6.8, respectively. Hypogonadism was exclusively associated with autoantibodies against SCC with an OR of 12.5. Autoantibodies against tyrosine phosphatase-like protein IA-2 were associated with insulin-dependent diabetes mellitus with an OR of 14.9, but with low sensitivity. Reactivities against TPH and, surprisingly, glutamic acid decarboxylase 65, were associated with intestinal dysfunction, with ORs of 3.9 and 6.7, respectively. TPH reactivity was the best predictor for autoimmune hepatitis, with an OR of 27.0. Hypoparathyroidism was not associated with reactivity against any of the autoantigens tested. No reactivity against the calcium-sensing receptor was found. Analysis of autoantibodies in autoimmune polyendocrine syndrome type I patients is a useful tool for establishing autoimmune manifestations of the disease as well as providing diagnosis in patients with suspected disease.
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