title: Digestive histopathological presentation of IPEX syndrome.
abstract: Immunodysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) syndrome is a well recognized and particularly severe form of autoimmune enteropathy. It has an X-linked recessive transmission, and is caused by mutations in the FOXP3 gene. We studied the intestinal morphological changes characterizing IPEX syndrome in a series of 12 children with a molecularly confirmed diagnosis. Histological examination of duodenal, gastric and colonic biopsies were retrospectively reviewed and compared by two independent experienced pathologists. In parallel, the presence of circulating anti-enterocyte antibodies was analysed using an indirect immunofluorescence technique and a quantitative radioligand assay against the 75-kDa autoantigen. The morphology of the inflammatory gut lesions could be categorized into three different entities, namely graft-vs-host disease-like changes (9/12 patients), a coeliac disease-like pattern (2/12) and an enteropathy with a complete depletion of goblet cells (1/12). Our results do not suggest any phenotype-genotype correlation. Circulating antibodies were detected in all 12 patients, with an anti-brush border pattern (11/12) and anti-goblet cell antibodies (1/12), as well as by a radioligand assay. The histological presentation of autoimmune enteropathy is rather variable. However, a graft-vs-host disease-like pattern associated with positive anti-enterocyte antibodies is the most frequent intestinal presentation of IPEX syndrome, and constitutes a very valuable tool for pathologists to suspect this diagnosis.
authors.affiliation: Department of Pathology, Necker-Enfants Malades, Université René Descartes Paris V, Tumorothèque, Paris, France. natalie.patey.hsj@ssss.gouv.qc.ca
authors.forename: Natacha
authors.initials: N
authors.lastname: Patey-Mariaud de Serre
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Soléne
authors.initials: S
authors.lastname: Ganousse
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
authors.forename: Frank
authors.initials: F
authors.lastname: Ruemmele
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D019084:Fluorescent Antibody Technique, Indirect; D051858:Forkhead Transcription Factors / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000276:immunology / Q000473:pathology; D006801:Humans; D007223:Infant; D007410:Intestinal Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008297:Male; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000276:immunology / Q000473:pathology*; D012189:Retrospective Studies; D013577:Syndrome
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors