Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations.
We herein report on two Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1). The brother, who expressed a characteristic phenotype of APS-1, had developed severe mucocutaneous candidiasis in early infancy and thereafter developed hypoparathyroidism and Addison's disease, along with a severe deterioration of his immunologic function. In contrast, the 44-year-old sister, who showed a noncharacteristic phenotype of APS-1, developed insulin-dependent diabetes with high anti-glutamic acid decarboxylase antibody, mild nail candidiasis, and autoimmune hepatitis with intact immunoreactivity. She had three susceptible human leukocyte antigen (HLA) loci for type 1 autoimmune diabetes. The expression of T cell receptor (TCR)V beta 5.1 increased in both patients, while the brother showed a widely suppressed expression of many TCRV beta families. Both individuals possessed compound heterozygous novel autoimmune regulator (AIRE) gene mutations (L29P and IVS9-1G > C). The same AIRE gene mutations can thus be associated with characteristic and noncharacteristic phenotypes of APS-1, and HLA may possibly influence the phenotype of APS-1.
Kogawa
Kazuhiko
K
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Japan.
Kudoh
Jun
J
Nagafuchi
Seiho
S
Ohga
Shouichi
S
Katsuta
Hitoshi
H
Ishibashi
Hiromi
H
Harada
Mine
M
Hara
Toshiro
T
Shimizu
Nobuyoshi
N
D000224:Addison Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000328:Adult; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007564:Japan; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein