Mahnaz Jamee1, Majid Zaki-Dizaji2, Bernice Lo3, Hassan Abolhassani4, Fatemeh Aghamahdi5, Mehdi Mosavian5, Zohreh Nademi6, Hamed Mohammadi5, Farhad Jadidi-Niaragh7, Manuel Rojas8, Juan-Manuel Anaya8, Gholamreza Azizi9. 1. Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran; Alborz Office of USERN, Universal Scientific Education and Research Network (USERN), Alborz University of Medical Sciences, Karaj, Iran. 2. Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran. 3. Sidra Medicine, Division of Translational Medicine, Research Branch, Doha, Qatar. 4. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. 5. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. 6. Children's Bone Marrow Transplant Unit, Great North Children's Hospital, Newcastle, United Kingdom. 7. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 8. Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia. 9. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. Electronic address: azizi@abzums.ac.ir.
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 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.
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.
Authors: Brian R Shy; Vivasvan S Vykunta; Alvin Ha; Alexis Talbot; Theodore L Roth; David N Nguyen; Wolfgang G Pfeifer; Yan Yi Chen; Franziska Blaeschke; Eric Shifrut; Shane Vedova; Murad R Mamedov; Jing-Yi Jing Chung; Hong Li; Ruby Yu; David Wu; Jeffrey Wolf; Thomas G Martin; Carlos E Castro; Lumeng Ye; Jonathan H Esensten; Justin Eyquem; Alexander Marson Journal: Nat Biotechnol Date: 2022-08-25 Impact factor: 68.164
Authors: Kelsey L Smith; Darlene Dai; Bhavi P Modi; Rahnuma Sara; Elizabeth Garabedian; Rebecca A Marsh; Jennifer Puck; Elizabeth Secord; Kathleen E Sullivan; Stuart E Turvey; Catherine M Biggs Journal: Front Immunol Date: 2022-02-22 Impact factor: 7.561