Premium
AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED
Author(s) -
Cervato Sara,
Morlin Luca,
Albergoni Maria Paola,
Masiero Stefano,
Greggio Nella,
Meossi Cristiano,
Chen Shu,
Del Pilar Larosa Maria,
Furmaniak Jadwiga,
Rees Smith Bernard,
Alimohammadi Mohammad,
Kämpe Olle,
Valenzise Mariella,
Betterle Corrado
Publication year - 2010
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2010.03862.x
Subject(s) - autoimmune regulator , autoantibody , hypoparathyroidism , medicine , immunology , haplotype , human leukocyte antigen , mutation , autoimmune disease , endocrinology , allele , autoimmunity , gene , biology , antigen , antibody , genetics
Summary Objective To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ‐ or non‐organ‐specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison’s disease (AD) or chronic candidiasis (CC). Design, Patients and Measurements Twenty‐four patients who had CH without AD or CC were included in the study. AIRE gene mutations in all 14 exons were studied using PCR in 24 patients, 105 healthy controls and 15 first‐degree relatives of CH patients with AIRE mutations. Human leucocyte antigens (HLA) were determined for all 24 patients and 105 healthy controls. Autoantibodies to a range of antigens including NACHT leucine‐rich‐repeat protein‐5 (NALP5) and interferon omega (IFNω) were tested in all 24 patients. Results AIRE gene mutations were found in 6 of 24 (25%) patients, all females, and this was significantly higher ( P < 0·001) compared with AIRE mutations found in healthy controls (2/105). Three patients (12·5%) had homozygous AIRE mutations characteristic of Autoimmune‐Poly‐Endocrinopathy‐Candidiasis‐Ectodermal‐Dystrophy and all three were also positive for IFNω‐autoantibodies. Three patients (12·5%) had heterozygous AIRE mutations; two of these were novel mutations. One of the patients with heterozygous AIRE mutations was positive for both NACHT leucine–rich‐repeat protein 5 and IFNω autoantibodies. Heterozygous AIRE mutations were found in 10 of 15 first‐degree relatives of CH patients with AIRE mutations, although none was affected by CH. Class II HLA haplotypes were not statistically different in patients with CH compared to healthy controls. Conclusions Analysis of AIRE gene mutations together with serum autoantibody profile should be helpful in the assessment of patients with CH, in particular young women with associated autoimmune diseases.