title: Autoantibodies to villin occur frequently in IPEX, a severe immune dysregulation, syndrome caused by mutation of FOXP3.
abstract: Intractable diarrhea is a major symptom of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome and associated with autoantibodies against enterocytes. Although autoimmune enteropathy (AIE)-related 75 kDa antigen (AIE-75) is a prominent autoantigen involved in the enteropathy associated with IPEX syndrome, some patients with this syndrome demonstrated autoantibody recognizing a 95 kDa protein rather than AIE-75 in the small intestine. We, herewith, identified villin, an actin-binding protein, as the 95 kDa antigen. Four of five sera from patients with IPEX syndrome reacted with a fusion protein of glutathione-S-transferase and full length villin (GST-villin), whereas only three of 98 control sera weakly reacted with GST-villin. Anti-AIE-75 antibody was detected in all five IPEX sera but not in normal or control disease sera. We conclude that both AIE-75 and villin appear to be brush border autoantigens in IPEX syndrome and could be used for the diagnosis of AIE in patients with presumptive IPEX syndrome.
authors: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan. ichikobaya@med.hokudai.ac.jp
authors: Ichiro
authors: I
authors: Kobayashi
authors: Mitsuru
authors: M
authors: Kubota
authors: Masafumi
authors: M
authors: Yamada
authors: Hiroshi
authors: H
authors: Tanaka
authors: Shuichi
authors: S
authors: Itoh
authors: Yoji
authors: Y
authors: Sasahara
authors: Luke
authors: L
authors: Whitesell
authors: Tadashi
authors: T
authors: Ariga
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D017931:DNA Primers / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008840:Microfilament Proteins / Q000276:immunology*; D008871:Microvilli / Q000276:immunology; D008970:Molecular Weight; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013577:Syndrome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; D001324:Autoantigens; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; C118970:USH1C protein, human; C026615:villin