Case Report: Atypical Manifestations Associated With FOXP3 Mutations. The “Fil Rouge” of Treg Between IPEX Features and Other Clinical Entities?

Frontiers in Immunology

Lorenzo Nescis¹  Enrico Fiaccadori²  Luca Lanino³  Daniela Fenoglio⁵  Edoardo La Porta⁶  Daniela Verzola⁷  Enrico Verrina⁸  Micaela Gentile⁹  Maurizio Miano^1,10  Paola Terranova^1,10  Maura Faraci^1,11  Filomena Pierri^1,11  Stefano Giardino^1,11  Gianluca Caridi^1,12  Barbara Cafferata^1,13  Gianmarco Ghiggeri^1,14  Enrico Drago^1,14  Andrea Angeletti^1,14  Francesca Lugani^1,14  Alice Grossi^1,15  Isabella Ceccherini^1,15 

[1] 0Unitá Operativa (UO) of Nephrology, Dialysis, and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Martino, Genoa, Italy;1Unitá Operativa (UO) Nefrologia, Azienda Ospedaliera-Universitaria, Parma, Italy;2Department of Oncology and Hematology, Humanitas Clinical and Research Center, Milan, Italy;3Biotherapy Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Martino, Genoa, Italy;4Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, Genoa, Italy;5Department of Internal Medicine, University of Genoa, Genoa, Italy;Department of Internal Medicine and Medical Specialties, University of Genova, Genoa, Italy;Dialysis Unit, Department of Pediatric, IRCCS Istituto Giannina Gaslini,Genoa, Italy;Dipartimento di Medicina e Chirurgia, Università di Parma, Parma, Italy;Hematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy;Hematopoietic Stem Cell Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy;Laboratory on Molecular Nephrology, Division of Nephrology, Dialysis, and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy;Pathology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy;Unitá Operativa (UO) of Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy;Unitá Operativa Semplice Dipartimentale (UOSD) Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy;

关键词: FOXP3;    ALPS;    IPEX;    membranous glomerulopathy;    regulatory T cells;    NGS;   

DOI  :  10.3389/fimmu.2022.854749

来源: DOAJ

【 摘 要 】

IntroductionThe Forkhead box protein P3 (FOXP3) is a transcription factor central to the function of regulatory T cells (Treg). Mutations in the FOXP3 gene lead to a systemic disease called immune dysregulation, polyendocrinopathy, and enteropathy, an X-linked syndrome (IPEX) characterized by the triad of early-onset intractable diarrhea, type 1 diabetes, and eczema. An atypical presentation of IPEX has been reported.MethodWe report rare cases with equivocal clinical associations that included inflammatory, kidney, and hematologic involvements screened with massively parallel sequencing techniques.ResultsTwo patients with hemizygous mutations of FOXP3 [c.779T>A (p.L260Q)] and [c.1087A>G (p.I363V)] presented clinical manifestations not included in typical cases of IPEX: one was a 16-year-old male patient with an initial clinical diagnosis of autoimmune lymphoproliferative syndrome (ALPS) and who developed proteinuria and decreased kidney function due to membranous nephropathy, an autoimmune renal condition characterized by glomerular sub-epithelial antibodies. The second patient was a 2-year-old child with bone marrow failure who developed the same glomerular lesions of membranous nephropathy and received a bone marrow transplantation. High levels of IgG4 in serum, bone marrow, and kidney led to the definition of IgG4-related kidney disease (IgG4 RKD) in this young boy. The circulating Treg levels were normal in the former case and very low in the second.ConclusionTwo atypical associations of functional mutations of FOXP3 that include ALPS and IgG4 RKD are described. Membranous nephropathy leading to renal failure completed in both cases the clinical phenotypes that should be included in the clinical panorama of FOXP3 failure.

【 授权许可】

Unknown