{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:29:50Z","timestamp":1790512190642,"version":"4.1.0"},"reference-count":22,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: 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\u2019s first manifestation generally is mucocutaneous candidiasis presumably related to T cell dysfunction.<\/jats:p>\n               <jats:p>Patient: 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.<\/jats:p>\n               <jats:p>Results: Genetic analysis revealed a large homozygous deletion (g.424_2157del1734), spanning exons 2\u20134, 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).<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1210\/jc.2005-1538","type":"journal-article","created":{"date-parts":[[2006,1,9]],"date-time":"2006-01-09T22:27:51Z","timestamp":1136845671000},"page":"192-195","source":"Crossref","is-referenced-by-count":47,"title":["Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome with Renal Failure: Impact of Posttransplant Immunosuppression on Disease Activity"],"prefix":"10.1210","volume":"91","author":[{"given":"Tim","family":"Ulinski","sequence":"first","affiliation":[{"name":"Departments of Pediatric Nephrology (T.U., L.P., A.B., G.D.), 75571 Paris Cedex 12, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Perrin","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Nephrology (T.U., L.P., A.B., G.D.), 75571 Paris Cedex 12, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics (M.M.), Centre Medical Universitaire, 1121 Gene\u0300ve, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Houang","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology (M.H., S.C.), 75571 Paris Cedex 12, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Cabrol","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology (M.H., S.C.), 75571 Paris Cedex 12, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Grapin","sequence":"additional","affiliation":[{"name":"Pediatric Surgery (C.G.), Ho\u0302pital Trousseau, 75571 Paris Cedex 12, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Chabbert-Buffet","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes (N.C.-B.), Ho\u0302pital Tenon, F-75970 Paris Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Bensman","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Nephrology (T.U., L.P., A.B., G.D.), 75571 Paris Cedex 12, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Desche\u0302nes","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Nephrology (T.U., L.P., A.B., G.D.), 75571 Paris Cedex 12, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Giurgea","sequence":"additional","affiliation":[{"name":"Department of Genetics (I.G.), Ho\u0302pital Henri Mondor, 94010 Cre\u0301teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071616570204100_R1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1399-0004.1985.tb02037.x","article-title":"Autoimmune polyendocrinopathy\u2014candidosis\u2014ectodermal dystrophy (APECED): autosomal recessive inheritance.","volume":"27","author":"Ahonen","year":"1985","journal-title":"Clin Genet"},{"key":"2020071616570204100_R2","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1056\/NEJM199006283222601","article-title":"Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients.","volume":"322","author":"Ahonen","year":"1990","journal-title":"N Engl J Med"},{"key":"2020071616570204100_R3","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s004390050846","article-title":"A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients.","volume":"103","author":"Rosatelli","year":"1998","journal-title":"Hum Genet"},{"key":"2020071616570204100_R4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00109-001-0306-2","article-title":"The genetic background of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and its autoimmune disease components.","volume":"80","author":"Vogel","year":"2002","journal-title":"J Mol Med"},{"key":"2020071616570204100_R5","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng1297-393","article-title":"Positional cloning of the APECED gene.","volume":"17","author":"Nagamine","year":"1997","journal-title":"Nat Genet"},{"key":"2020071616570204100_R6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/07853899708998786","article-title":"Cloning of the APECED gene provides new insight into human autoimmunity.","volume":"31","author":"Aaltonen","year":"1999","journal-title":"Ann Med"},{"key":"2020071616570204100_R7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0968-0004(98)01231-6","article-title":"The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor.","volume":"23","author":"Gibson","year":"1998","journal-title":"Trends Biochem Sci"},{"key":"2020071616570204100_R8","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1006\/bbrc.1999.0223","article-title":"Isolation and characterization of the mouse Aire gene.","volume":"255","author":"Mittaz","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071616570204100_R9","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1093\/hmg\/8.2.277","article-title":"AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered sub-cellular distribution of mutants lacking the PHD zinc fingers.","volume":"8","author":"Rinderle","year":"1999","journal-title":"Hum Mol 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