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Clinical, Immunological, and Genetic Features in Patients with Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) and IPEX-like Syndrome

      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 patients with IPEX and IPEX-like syndrome to delineate differences in these 2 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 the IPEX and IPEX-like groups.

      Results

      A total of 459 patients were reported in 148 eligible articles. Major clinical differences between patients with IPEX and IPEX-like syndrome were observed in rates of pneumonia (11% vs 31%, P < .001), bronchiectasis (0.3% vs 14%, P < .001), diarrhea (56% vs 42%, P = .020), and organomegaly (10% vs 23%, P = .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 patients with IPEX and IPEX-like syndrome, respectively. In the IPEX group, a lower mortality rate was observed among patients receiving hematopoietic stem cell transplantation (HSCT) (24%) compared with other patients (43%), P = .008; however, in the IPEX-like group, it was not significant (P = .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 common variable immunodeficiency–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.

      Key words

      Abbreviations used:

      CMCC (Chronic mucocutaneous candidiasis), FOXP3 (Forkhead box P3), GOF (Gain-of-function), HSCT (Hematopoietic stem cell transplantation), IDDM (Insulin-dependent diabetes mellitus), IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked), IQR (Interquartile range), Treg (Regulatory T cell), DOCK8 (Dedicator of cytokinesis 8), LRBA (Lipopolysaccharide (LPS)-responsive and beige-like anchor), MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1), STAT (Signal transducer and activator of transcription)
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