AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED.
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).


METHODS
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.
Cervato
Sara
S
Department of Medical and Surgical Sciences Blood Transfusion Center, Azienda Ospedaliera-Università di Padova, Padova, Italy.
Morlin
Luca
L
Albergoni
Maria Paola
MP
Masiero
Stefano
S
Greggio
Nella
N
Meossi
Cristiano
C
Chen
Shu
S
del Pilar Larosa
Maria
M
Furmaniak
Jadwiga
J
Rees Smith
Bernard
B
Alimohammadi
Mohammad
M
Kämpe
Olle
O
Valenzise
Mariella
M
Betterle
Corrado
C
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006680:HLA Antigens / Q000097:blood; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics* / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
D001323:Autoantibodies; D006680:HLA Antigens; D007370:Interferon Type I; D014157:Transcription Factors; D000096927:AIRE Protein; C063743:interferon omega 1