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Prevalence and Clinical Associations of 10 Defined Autoantibodies in Autoimmune Polyendocrine Syndrome Type I

Department of Medical Sciences (A.S., O.E., G.G.-M., H.H., E.L., F.R., O.K., T.N.) and Department of Women’s and Children’s Health (J.G.), University Hospital, SE-751 85 Uppsala, Sweden; Department of Bacteriology and Immunology, Haartman Institute, University Hospital and University of Helsinki (A.M., M.G.), FIN-00014 Helsinki, Finland; Department of Human Molecular Genetics, National Public Health Institute, and The Hospital for Children and Adolescents (P.E., M.H., J.P.), University of Helsinki, FIN-00290, Helsinki, Finland; Department of Medicine (T.T.), University Hospital, FIN-00290, Helsinki, Finland; Department of Medicine (E.S.H., A.G.M.), Haukeland University Hospital, N-5021 Bergen, Norway; Department of Pediatrics (A.G.M.), Akershus University Hospital, N-1474 Nordbyhagen, Norway; and Department of Gastroenterology and Hepatology (M.P.M.), Hannover Medical School, D-30625 Hannover, Germany

Address all correspondence and requests for reprints to: Thomas Nilsson, M.D., Ph.D., Department of Medical Sciences, University Hospital, Uppsala University, SE-751 85 Uppsala, Sweden. E-mail: thomas.nilsson{at}medsci.uu.se.

The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17-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.

This work was supported by grants from the Swedish Medical Research Council, the Torsten and Ragnar Söderberg Foundation, the Petrus and Augusta Hedlund Foundation, Tore Nilson Foundation, the Förenade Liv Mutual Group Life Insurance Company, the Swedish Cancer Society, the Aagot Giertsen’s Fund, and the Norwegian Diabetes Association.

Abbreviations: AADC, Aromatic L-amino acid decarboxylase; AIRE, autoimmune regulator; APECED, autoimmune polyendocrinpathy-candidiasis-ectodermal dystrophy; APS I, autoimmune polyendocrine syndrome type I; CaSR, calcium-sensing receptor; CYP1A2, cytochrome P450 1A2; CYP2A6, cytochrome P450 2A6; GAD65, glutamic acid decarboxylase 65; IA-2, protein IA-2; IDDM, insulin-dependent diabetes mellitus; 17-OH, 17-hydroxylase; 21-OH, 21-hydroxylase; OR, odds ratio; SCC, side-chain cleavage enzyme; TH, tyrosine hydroxylase; TPH, tryptophan hydroxylase.

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