title: Clinical heterogeneity of immunodysregulation, polyendocrinopathy, enteropathy, X-linked: pulmonary involvement as a non-classical disease manifestation.
abstract: OBJECTIVE
  IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) is a rare X-linked recessive life-threatening disorder characterized by autoimmunity and early death. Pulmonary complication related with IPEX has not been elucidated exactly. Here, we report 4 IPEX patients, 3 of which died from severe pulmonary disease.
  
  
  METHODS
  Clinical data and laboratory findings including autoantibodies, immunoglobulin levels as well as number of T, B and NK cells were evaluated. FOXP3 expression and T reg activity were analyzed. The FOXP3 gene was sequenced and RNA analysis was performed.
  
  
  RESULTS
  Patient I (PI) presented with nephrotic syndrome at 3 years of age and then developed autoimmune hepatitis without eczema, enteropathy or high IgE and died at 9 years of age due to acute respiratory distress syndrome (ARDS). Two cousins of PI had the same hypomorphic splice site mutation leading to a deletion of 27 amino acids, but normal FOXP3 protein expression and normal suppressive capacity of T reg in a proliferation inhibition assay. However, they exhibited typical symptoms such as eczema, diabetes and enteropathy with eosinophilia at early age (PII, PIII) and were transplanted in infancy. One of them had severe respiratory distress right after birth (PIII). Patient IV from another family presented with chronic diarrhea without autoimmune manifestations and died due to ARDS.
  
  
  CONCLUSIONS
  Lung disease related to IPEX syndrome has not been reported before and this entity could be a critical factor in disease outcome.
authors.affiliation: Division of Pediatric Allergy and Immunology, Marmara Medical Faculty, Istanbul, Turkey, safabaris@hotmail.com.
authors.forename: Safa
authors.initials: S
authors.lastname: Baris
authors.forename: Ilka
authors.initials: I
authors.lastname: Schulze
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozen
authors.forename: Elif
authors.initials: E
authors.lastname: Karakoç Aydıner
authors.forename: Emel
authors.initials: E
authors.lastname: Altuncu
authors.forename: Gulsun Tezcan
authors.initials: GT
authors.lastname: Karasu
authors.forename: Nilufer
authors.initials: N
authors.lastname: Ozturk
authors.forename: Myriam
authors.initials: M
authors.lastname: Lorenz
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Thomas
authors.initials: T
authors.lastname: Vraetz
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
authors.forename: Isil B
authors.initials: IB
authors.lastname: Barlan
mesh_terms: D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000151:congenital; D003967:Diarrhea; D017809:Fatal Outcome; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007154:Immune System Diseases / Q000151:congenital; D007108:Immune Tolerance / Q000235:genetics; D007223:Infant; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D012128:Respiratory Distress Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014421:Turkey
chemical_list: D001323:Autoantibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors