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Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review

 Jae Hyon Park  ;  Keum Hwa Lee  ;  Bokyoung Jeon  ;  Hans D Ochs  ;  Joon Suk Lee  ;  Heon Yung Gee  ;  Seeun Seo  ;  Dongil Geum  ;  Ciriaco A Piccirillo  ;  Michael Eisenhut  ;  Hans J van der Vliet  ;  Jiwon M Lee  ;  Andreas Kronbichler  ;  Younhee Ko  ;  Jae Il Shin 
 AUTOIMMUNITY REVIEWS, Vol.19(6) : 102526, 2020-06 
Journal Title
Issue Date
Forkhead Transcription Factors / genetics ; Genetic Diseases, X-Linked* / immunology ; Genetic Diseases, X-Linked* / pathology ; Humans ; Immune System Diseases* / immunology ; Immune System Diseases* / pathology ; Intestinal Diseases* / immunology ; Intestinal Diseases* / pathology ; Mutation ; Polyendocrinopathies, Autoimmune* / immunology ; Polyendocrinopathies, Autoimmune* / pathology ; Syndrome ; T-Lymphocytes, Regulatory / immunology
Enteropathy ; FOXP3 mutation ; Genotype-phenotype correlation ; Immune dysregulation ; Polyendocrinopathy ; Systematic review ; X-linked (IPEX) syndrome
Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder characterized by early onset fatal multi-system autoimmunity due to loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor which is crucial for the development, maturation, and maintenance of CD4+ regulatory T (T-reg) cells. Various autoimmune phenomena such as enteropathy, endocrinopathies, cytopenias, renal disease, and skin manifestations are characteristic findings in patients affected by IPEX syndrome. Objectives: In this systematic review, we focus on both clinical and demographic characteristics of IPEX patients, highlighting possible genotype-phenotype correlations and address prognostic factors for disease outcome. Methods: We performed a literature search to systematically investigate the case reports of IPEX which were published before August 7th, 2017. Results: A total of 75 articles (195 patients) were identified. All IPEX patients included had FOXP3 mutations which were most frequently located in the forkhead domain (n = 68, 34.9%) followed by the leucine-zipper domain (n = 30, 15.4%) and repressor domain (n = 36, 18.4%). Clinical manifestations were as follows: enteropathy (n = 191, 97.9%), skin manifestations (n = 121, 62.1%), endocrinopathy (n = 104, 53.3%), hematologic abnormalities (n = 75, 38.5%), infections (n = 78, 40.0%), other immune-related complications (n = 43, 22.1%), and renal involvement (n = 32, 16.4%). Enteropathic presentations (P = 0.017), eczema (P = 0.030), autoimmune hemolytic anemia (P = 0.022) and food allergy (P = 0.009) were associated with better survival, while thrombocytopenia (P = 0.034), septic shock (P = 0.045) and mutations affecting the repressor domain (P = 0.021), intron 7 (P = 0.033) or poly A sequence (P = 0.025) were associated with increased risk of death. Immunosuppressive therapy alone was significantly associated with increased cumulative survival compared to patients who received no treatment (P = 0.041). Conclusions: We report the most comprehensive summary of demographic and clinical profiles derived from a total of 195 IPEX patients with deleterious mutations in FOXP3. Analysis of our findings provides new insights into genotype/phenotype correlations, and clinical and genetic factors associated with increased risk of death and response to treatment strategies.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
Lee, Keum Hwa(이금화) ORCID logo https://orcid.org/0000-0002-1511-9587
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
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