Autoimmune polyendocrine syndrome type 1 in north-western France: AIRE gene mutation specificities and severe forms needing immunosuppressive therapies.
BACKGROUND
Autoimmune polyendocrine syndrome type 1 (APS1) has been poorly evaluated in France. We focused on the north-western part of the country to describe clinical phenotypes, especially severe forms of the disease, and AIRE gene mutations.


METHODS
Clinical and immunological data were collected, and pathological mutations were identified by DNA sequencing.


RESULTS
Nineteen patients were identified with APS1. Clinical manifestations varied greatly, showing 1-10 components. Mucocutaneous candidiasis, adrenal failure, hypoparathyroidism, alopecia and other severe infections were the most frequent components. Four patients had severe forms, needing immunosuppressive therapy: 2 for hepatitis; 1 for severe malabsorption, and 1 for a T cell large granular lymphocytic leukemia. These therapies were very effective but caused general discomfort. One patient died of septicemia. Four different AIRE gene mutations were identified, and a 13-bp deletion in exon 8 (c.967-979del13) was the most prevalent. There was at least one allele correlating with this mutation and alopecia occurrence (p = 0.003). No novel mutation was detected.


CONCLUSIONS
APS1 appears to be rare in north-western France. We identified 4 cases with a severe form needing immunosuppressive therapy. The AIRE gene mutations are more like those found in north-western Europe than those found in Finland.
Proust-Lemoine
E
E
Saugier-Véber
P
P
Lefranc
D
D
Dubucquoi
S
S
Ryndak
A
A
Buob
D
D
Lalau
J D
JD
Desailloud
R
R
Weill
J
J
Prin
L
L
Lefebvre
H
H
Wémeau
J L
JL
D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000453:epidemiology / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005602:France / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000096927:AIRE Protein
D007166:Immunosuppressive Agents; D014157:Transcription Factors; D000096927:AIRE Protein