Abstract
Autoantibodies to enterocyte antigens harmonin (75 kDa USH1C protein) and villin (actin-binding 95 kDa protein) are associated with the Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome. In this study we evaluated the diagnostic value of harmonin and villin autoantibodies in IPEX and IPEX-like syndromes. Harmonin and villin autoantibodies were measured by a novel Luminescent-Immuno-Precipitation-System (LIPS) quantitative assay, in patients with IPEX, IPEX-like syndrome, Primary Immunodeficiencies (PID) with enteropathy, all diagnosed by sequencing of the FOXP3 gene, and in type 1 diabetes (T1D), celiac disease and healthy blood donors as control groups. Harmonin and villin autoantibodies were detected in 12 (92%) and 6 (46%) of 13 IPEX patients, and in none of the IPEX-like, PID, T1D, celiac patients, respectively. All IPEX patients, including one case with late and atypical clinical presentation, had either harmonin and/or villin autoantibodies and tested positive for enterocyte antibodies by indirect immunofluorescence. When measured in IPEX patients in remission after immunosuppressive therapy or hematopoietic stem cell transplantation, harmonin and villin autoantibodies became undetectable or persisted at low titers in all cases but one in whom harmonin autoantibodies remained constantly high. In one patient, a peak of harmonin antibodies paralleled a relapse phase of enteropathy. Our study demonstrates that harmonin and villin autoantibodies, measured by LIPS, are sensitive and specific markers of IPEX, differentiate IPEX, including atypical cases, from other early childhood disorders associated with enteropathy, and are useful for screening and clinical monitoring of affected children.
Highlights
Immune dysregulation, Polyendocrinopathy, Enteropathy, Xlinked (IPEX) syndrome is a monogenic autoimmune disease characterized by severe enteropathy, type 1 diabetes (T1D) and eczema [1,2]
We investigated 5 patients with primary immunodeficiencies (PID) of different origin [two with CD25 deficiency, two with Wiskott Aldrich Syndrome (WAS) and one with adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID), all conditions characterized by early onset enteropathy], 123 with T1D, 70 with celiac disease and 123 healthy blood donors
Patients with T1D were all recent onset cases, with diagnosis based on the American Diabetes Association criteria [21]; patients with celiac disease were all studied at the time of diagnosis based on jejunal biopsy
Summary
Polyendocrinopathy, Enteropathy, Xlinked (IPEX) syndrome is a monogenic autoimmune disease characterized by severe enteropathy, type 1 diabetes (T1D) and eczema [1,2]. Circulating enterocyte autoantibodies, detected by indirect immunofluorescence, were described in the past in association with a variety of enteropathies, including those eventually identified as IPEX syndrome [7], but the molecular targets of these serological markers have long been unknown. The actin-binding 95 kDa protein denominated villin, involved in the organization of actin cytoskeleton in the brush border of epithelial cells [15], was described as an additional target of autoantibodies in a proportion of patients with IPEX [16]. To our knowledge, no information has been reported either on HAA, or villin autoantibodies (VAA) in IPEX-like syndromes, primary immunodeficiencies (PID) with enteropathy or in disorders frequently associated to IPEX, such as T1D and autoimmune enteropathies of different origin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
