Clinical, immunological, and genetic features in patients with Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) and IPEX-like Syndrome.

Abstract

BACKGROUND: Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare inborn error of immunity caused by mutations in the forkhead box P3 (FOXP3) gene.OBJECTIVE: In this study, we conducted a systematic review of IPEX and IPEX-like patients to delineate differences in these two major groups.METHODS: The literature search was performed in PubMed, Web of Science and Scopus databases and demographic, clinical, immunologic, and molecular data were compared between IPEX (n= 312) and IPEX-like (n= 98) groups.RESULTS: A total of 459 patients were reported in 148 eligible articles. Major clinical differences between IPEX and IPEX-like patients were observed in rates of pneumonia (11% vs. 31%, p<0.001), bronchiectasis (0.3% vs. 14%, p<0.001), diarrhea (56% vs. 42%, p=0.020), and organomegaly (10% vs. 23%, p=0.001), respectively. Eosinophilia (95% vs. 100%), low regulatory T cell count (68% vs. 50%), and elevated IgE (87% vs. 61%) were the most prominent laboratory findings in IPEX and IPEX-like patients, respectively. In IPEX group, a lower mortality rate was observed among patients receiving HSCT (24%) compared to other patients (43%), p=0.008, however, in IPEX-like group it was not significant (p=0.189).CONCLUSIONS: Patients with IPEX syndrome generally suffer from enteropathy, autoimmunity, dermatitis, eosinophilia, and elevated serum IgE. Despite similarities in their clinical presentations, patients with IPEX-like syndrome are more likely to present CVID-like phenotype such as respiratory tract infections, bronchiectasis, and organomegaly. HSCT is currently the only curative therapy for both IPEX and IPEX-like syndrome and may result in favorable outcome.