Identification of autoimmune polyendocrine syndrome type 1 in patients with isolated hypoparathyroidism
2016 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 85, no 4, 544-550 p.Article in journal (Refereed) Published
Objective The prevalence of autoimmune polyendocrine syndrome type 1 (APS1) among isolated hypoparathyroidism (HP) or primary adrenal insufficiency (PAI) is not well established. We studied the frequency of APS1 in patients with HP or PAI by measuring interferon-alpha (IFN-alpha) antibody levels, a highly sensitive and specific marker for APS1. Design, patients and measurements In a single-centre cross-sectional study, 37 Indian patients with isolated HP and 40 patients with PAI were tested for IFN-alpha antibody using an indirect ELISA. In patients with elevated IFN-alpha antibody, the autoimmune regulator (AIRE) gene was bidirectionally sequenced. Results Three (8.1%) patients with isolated HP had elevated IFN-alpha antibody levels (range: 367-17382 units; positive titre >56 units). Homozygous or compound heterozygous AIRE mutations were detected in all three patients, including a novel mutation (p.T68P). All three APS1 patients had atypical features. The first patient, diagnosed at 7 years of age, died suddenly 5 months later. The second patient had late-onset HP (at the age of 34 years) and a solitary episode of transient mucocutaneous candidiasis 5 years later. The final patient developed HP at the age of 14 years and premature ovarian insufficiency 14 years later. Interleukin-22 antibodies, as well as most other organ-specific antibodies, were absent in the 3 APS1 patients. All patients with PAI were negative for IFN-alpha antibody. Conclusion Eight percentage of patients with isolated HP had elevated IFN-alpha antibody levels and AIRE mutation-positive APS1. All APS1 patients had atypical clinical features. Testing for IFN-alpha antibody should be considered in patients with idiopathic HP.
Place, publisher, year, edition, pages
2016. Vol. 85, no 4, 544-550 p.
Endocrinology and Diabetes Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-307722DOI: 10.1111/cen.13111ISI: 000385821400005PubMedID: 27219120OAI: oai:DiVA.org:uu-307722DiVA: diva2:1048482
FunderSwedish Research CouncilTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseNovo Nordisk