title: The hypoparathyroidism of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protective effect of male sex.
abstract: 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 Ca(2+)-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.
authors.affiliation: Department of Bacteriology and Immunology, University of Helsinki, FIN-00014 Helsinki, Finland.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Gylling
authors.forename: Essi
authors.initials: E
authors.lastname: Kääriäinen
authors.forename: Riitta
authors.initials: R
authors.lastname: Väisänen
authors.forename: Laura
authors.initials: L
authors.lastname: Kerosuo
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Solin
authors.forename: Leena
authors.initials: L
authors.lastname: Halme
authors.forename: Seppo
authors.initials: S
authors.lastname: Saari
authors.forename: Maria
authors.initials: M
authors.lastname: Halonen
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.forename: Jaakko
authors.initials: J
authors.lastname: Perheentupa
authors.forename: Aaro
authors.initials: A
authors.lastname: Miettinen
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007011:Hypoparathyroidism / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D015994:Incidence; D008297:Male; D010280:Parathyroid Glands / Q000276:immunology; D010281:Parathyroid Hormone / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000276:immunology; D017678:Sex Distribution; D014157:Transcription Factors / Q000235:genetics; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D000096927:AIRE Protein; C069051:HLA-DQB1 antigen