Novel sequence variation of AIRE and detection of interferon-omega antibodies in early infancy.
OBJECTIVE
Autoimmune polyendocrine syndrome type I (APS I) is a rare primary immunodeficiency disorder characterized by chronic mucocutaneous candidiasis, multi-organ autoimmunity and ectodermal dysplasia. Autoantibodies to parathyroid and adrenal glands and type I interferons (IFN) are hallmarks of APS I, which results from mutations in the autoimmune regulator (AIRE) gene. We wished to study clinical, immunological and genetic features of APS I in Hungarian patients, and to correlate anti-IFN-omega serum concentration with APS I and other multi-organ autoimmune diseases.


METHODS
Detailed analysis of patients with APS I and multi-organ autoimmune diseases.


METHODS
Seven patients with APS I and 11 patients with multi-organ autoimmune diseases were studied.


METHODS
Mutational analysis was performed by bidirectional sequencing of AIRE. Antibodies against IFN-omega and endocrine organ-specific autoantigens were studied with radioimmunoassay. RFLP was performed by digestion of DNA with Hin6I restriction enzyme.


RESULTS
AIRE sequence analysis revealed homozygous c.769C>T mutations in three patients and compound heterozygous sequence variants (c.769C>T/c.44_66dup26bp; c.769C>T/c.965_977del13bp; c.769C>T/c.1344delC) in four patients with APS I. All the six live patients tested had markedly elevated IFN-omega antibodies, which were not found in heterozygous siblings or parents. One of the identified patients was negative for antibodies against IFN-omega at 6 weeks of age, but became positive at 7 months. At age 1, he is still without symptoms of the disease. In contrast to patients with APS I, no AIRE mutation or elevation of IFN-omega antibodies were detected in patients with multi-organ autoimmune diseases.


CONCLUSIONS
This is the first overview of patients diagnosed with APS I in Hungary. A novel c.1344delC mutation in AIRE was detected. Anti-IFN-omega antibodies seem to appear very early in life and are helpful to differentiate APS I from other multi-organ autoimmune diseases.
Department of Infectious and Pediatric Immunology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Beáta
B
Tóth
Anette S B
AS
Wolff
Zita
Z
Halász
Attila
A
Tar
Péter
P
Szüts
István
I
Ilyés
Melinda
M
Erdos
Gyula
G
Szegedi
Eystein S
ES
Husebye
Margit
M
Zeher
László
L
Maródi
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D007370:Interferon Type I / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011863:Radioimmunoassay; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000096927:AIRE Protein
D001323:Autoantibodies; D007370:Interferon Type I; D014157:Transcription Factors; D000096927:AIRE Protein; C063743:interferon omega 1