This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gylling, M. Articles by Miettinen, A. Search for Related Content PubMed PubMed Citation Articles by Gylling, M. Articles by Miettinen, A.

The Hypoparathyroidism of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Protective Effect of Male Sex

Department of Bacteriology and Immunology (M.G., E.K., L.K., A.M.), University of Helsinki, FIN-00014 Helsinki, Finland; Department of Immunology (M.G., R.V., L.K., M.-L.S., A.M.), Helsinki University Central Hospital Laboratory Diagnostics, FIN-00290 Helsinki, Finland; Department of Surgery (L.H.), Helsinki University Hospital, FIN-00014 Helsinki, Finland; National Veterinary and Food Research Institute (S.S.), FIN-00581 Helsinki, Finland; Department of Molecular Medicine (M.H.), National Public Health Institute, FIN-00300 Helsinki, Finland; Department of Medical Science (O.K.), University Hospital, SE-75185, Uppsala, Sweden; and The Hospital for Children and Adolescents (M.H., J.P.), University of Helsinki, FIN-00290 Helsinki, Finland

Address all correspondence and requests for reprints to: Aaro Miettinen, M.D., Ph.D., Department of Bacteriology and Immunology, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), FIN-00014 University of Helsinki, Finland. E-mail: aaro.miettinen{at}helsinki.fi.

In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, hypoparathyroidism (HP) is the most common endocrine component. It occurs in most (but not all) patients. Determinants of its occurrence are unknown, and there is no proof for its autoimmune nature. Recently, the Ca²⁺-sensing receptor (CaSR) was reported to be an autoantigen in HP. With our group of 90 patients, we aimed at identifying the determinants and pathomechanism of HP. For the determinants, we evaluated gender and the HLA class II. For the pathomechanism, we searched for parathyroid autoantibodies, including antibodies against CaSR and PTH. Also, we studied whether AIRE is expressed in the human parathyroid, because its absence could be a pathogenetic factor. We found a clear gender linkage with lower and later incidence in males. Of the 14 patients who had escaped HP, 13 were males. This was associated with adrenal failure, which was the first or only endocrinopathy in 47% of males vs. 7% of females. In contrast, we found no linkage to the HLA class II. By immunofluorescence, 19% of the patients had antibodies to parathyroid epithelia. By immunoblotting, these recognized several parathyroid proteins. No antibodies were observed against the CaSR or PTH. By RT-PCR, AIRE mRNA was not found in the parathyroid.

This work was supported by grants from Sigrid Jusélius Foundation, Finska Läkarsällskapet, Päivikki and Sakari Sohlberg Foundation, and The Helsinki University Hospital.

Abbreviations: AF, Adrenocortical failure; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; CaSR, Ca²⁺-sensing receptor; FITC, fluorescein isothiocyanate; HP, hypoparathyroidism; IF, immunofluorescence; IHP, idiopathic HP; PBS-T, Tween 20 in PBS; PG, parathyroid gland.

This article has been cited by other articles:

				M. Alimohammadi, P. Bjorklund, A. Hallgren, N. Pontynen, G. Szinnai, N. Shikama, M. P. Keller, O. Ekwall, S. A. Kinkel, E. S. Husebye, et al. Autoimmune Polyendocrine Syndrome Type 1 and NALP5, a Parathyroid Autoantigen N. Engl. J. Med., March 6, 2008; 358(10): 1018 - 1028. [Abstract] [Full Text] [PDF]

				N. G. Gavalas, E. H. Kemp, K. J. E. Krohn, E. M. Brown, P. F. Watson, and A. P. Weetman The Calcium-Sensing Receptor Is a Target of Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1 J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2107 - 2114. [Abstract] [Full Text] [PDF]

				R. Goswami, R. K. Marwaha, D. Goswami, N. Gupta, D. Ray, N. Tomar, and S. Singh Prevalence of Thyroid Autoimmunity in Sporadic Idiopathic Hypoparathyroidism in Comparison to Type 1 Diabetes and Premature Ovarian Failure J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4256 - 4259. [Abstract] [Full Text] [PDF]

				S. Hassler, C. Ramsey, M. C. Karlsson, D. Larsson, B. Herrmann, B. Rozell, M. Backheden, L. Peltonen, O. Kampe, and O. Winqvist Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma Blood, September 15, 2006; 108(6): 1941 - 1948. [Abstract] [Full Text] [PDF]

				J. Perheentupa Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2843 - 2850. [Abstract] [Full Text] [PDF]

				J J Corrales, M Almeida, R Burgo, M T Mories, J M Miralles, and A Orfao Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency. J. Endocrinol., June 1, 2006; 189(3): 595 - 604. [Abstract] [Full Text] [PDF]