Mahmood Tavassoli1, Hassan Abolhassani2,3, Reza Yazdani2, Mohsen Ghadami4, Gholamreza Azizi5, Sina Abdolrahim Poor Heravi5, Tannaz Moeini Shad2, Mostafa Kokabee2, Masoud Movahedi6, Hormoz Abdshahzadeh2, Mohammad Gharagozlou6, Nima Rezaei2,7, Hossein Esmaeilzadeh8, Soheila Aleyasin8, Asghar Aghamohammadi1. 1. Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 2. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. 4. Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. 6. Department of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 7. Network for Immunology in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 8. Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Abstract
BACKGROUND: Hyper-IgE syndromes (HIES) are distinct diseases characterized by recurrent cutaneous and lung infections, eczema, and elevated serum IgE level. METHODS: In this study, clinical manifestations, immunologic findings, and genetic studies of all patients with HIES in the Iranian national registry database were evaluated. RESULTS: A total of 129 HIES patients with a median age of 14.0 (9.0-24.0) years were followed up for a total of 307.8 patient-years. Genetic studies showed heterozygous STAT3 mutations in 19 patients and homozygous DOCK8 mutation in 16 patients. The mean of National Institutes of Health score in STAT3-deficient patients was higher than in patients with DOCK8 mutation (P = 0.001). It was shown that the presence of pneumatocele and hematologic complication were significantly frequent in STAT3-deficient cases compared to patients with DOCK8 deficiency (P = 0.001 and P = 0.002, respectively). Moreover, the median IgE serum levels were higher in patients with STAT3 gene mutation than in patients with DOCK8 gene mutation (P = 0.02). The eosinophils' count was enhanced in patients with DOCK8 deficiency than in patients with STAT3 gene defects (P = 0.02). CONCLUSION: Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease. Since HIES showed the highest rate of unsolved combined immunodeficiency, investigation of other genetic and environmental factors could also help in understanding the mechanism of remaining patients as well as providing strategy into therapeutic modalities.
BACKGROUND:Hyper-IgE syndromes (HIES) are distinct diseases characterized by recurrent cutaneous and lung infections, eczema, and elevated serum IgE level. METHODS: In this study, clinical manifestations, immunologic findings, and genetic studies of all patients with HIES in the Iranian national registry database were evaluated. RESULTS: A total of 129 HIESpatients with a median age of 14.0 (9.0-24.0) years were followed up for a total of 307.8 patient-years. Genetic studies showed heterozygous STAT3 mutations in 19 patients and homozygous DOCK8 mutation in 16 patients. The mean of National Institutes of Health score in STAT3-deficientpatients was higher than in patients with DOCK8 mutation (P = 0.001). It was shown that the presence of pneumatocele and hematologic complication were significantly frequent in STAT3-deficient cases compared to patients with DOCK8 deficiency (P = 0.001 and P = 0.002, respectively). Moreover, the median IgE serum levels were higher in patients with STAT3 gene mutation than in patients with DOCK8 gene mutation (P = 0.02). The eosinophils' count was enhanced in patients with DOCK8 deficiency than in patients with STAT3 gene defects (P = 0.02). CONCLUSION: Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease. Since HIES showed the highest rate of unsolved combined immunodeficiency, investigation of other genetic and environmental factors could also help in understanding the mechanism of remaining patients as well as providing strategy into therapeutic modalities.
Authors: Joëlle Khourieh; Peng Zhang; Franck Rapaport; Qian Zhang; Anne Puel; Vivien Béziat; Jean-Laurent Casanova; Bertrand Boisson; Takaki Asano; András N Spaan; Juan Li; Wei-Te Lei; Simon J Pelham; David Hum; Maya Chrabieh; Ji Eun Han; Antoine Guérin; Joseph Mackie; Sudhir Gupta; Biman Saikia; Jamila E I Baghdadi; Ilham Fadil; Aziz Bousfiha; Tanwir Habib; Nico Marr; Luckshman Ganeshanandan; Jane Peake; Luke Droney; Andrew Williams; Fatih Celmeli; Nevin Hatipoglu; Tayfun Ozcelik; Capucine Picard; Laurent Abel; Stuart G Tangye; Stéphanie Boisson-Dupuis Journal: J Exp Med Date: 2021-06-17 Impact factor: 14.307