Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome with renal failure: impact of posttransplant immunosuppression on disease activity.
BACKGROUND
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the gene AIRE (autoimmune regulator). APECED affects mainly endocrine organs resulting in hypoparathyroidism, adrenocortical failure, diabetes mellitus, hypogonadism, and hypothyroidism. Nonendocrine organ manifestations are autoimmune hepatitis, vitiligo, pernicious anemia, exocrine pancreatic insufficiency, and alopecia. APECED's first manifestation generally is mucocutaneous candidiasis presumably related to T cell dysfunction.


METHODS
A 5-yr-old Iranian girl presented first with pernicious anemia, exocrine pancreatic insufficiency, and nail candidiasis. She had renal dysfunction due to chronic interstitial nephritis (CIN), which progressed to end-stage renal failure. She was transplanted 1 yr later. Common causes of CIN were excluded. APECED was suspected first because she developed progressively hypoparathyroidism, adrenocortical failure, glucose intolerance, and hypothyroidism.


RESULTS
Genetic analysis revealed a large homozygous deletion (g.424_2157del1734), spanning exons 2-4, in the AIRE gene. The predicted protein, if it is produced, has only 44 amino acids (exon 1) in common with the wild-type protein. Immunosuppression after the first renal transplant included prednisone, azathioprine, and cyclosporine A. Multiple acute rejection episodes occurred. Chronic rejection resulted in lost graft and she was retransplanted 2 yr later. Surprisingly, all APECED-related symptoms including candidiasis and autoantibody levels decreased, presumably due to the reinforced immunosuppression (tacrolimus, mycophenolate mofetil, prednisone).


CONCLUSIONS
This is the first report of an APECED patient with CIN resulting in end-stage renal failure. Clinical and biological improvement was observed under posttransplant multidrug immunosuppression including tacrolimus and mycophenolate mofetil.
Ulinski
Tim
T
Department of Pediatric Nephrology, Hôpital Trousseau, 75571 Paris Cedex 12, France. tim.ulinski@trs.aphp.fr
Perrin
Laurence
L
Morris
Michael
M
Houang
Muriel
M
Cabrol
Sylvie
S
Grapin
Christine
C
Chabbert-Buffet
Nathalie
N
Bensman
Albert
A
Deschênes
Georges
G
Giurgea
Irina
I
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000601:surgery*; D016030:Kidney Transplantation; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications* / Q000235:genetics / Q000601:surgery*; D012640:Seizures / Q000150:complications / Q000188:drug therapy; D013601:T-Lymphocytes / Q000276:immunology
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents