Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency.

Autor: Abolhassani H; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran; Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden., Chou J; Division of Immunology Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass., Bainter W; Division of Immunology Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass., Platt CD; Division of Immunology Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass., Tavassoli M; Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute of Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran., Momen T; Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute of Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran., Tavakol M; Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran., Eslamian MH; Department of Pediatrics, Hamadan University of Medical Sciences, Hamadan, Iran., Gharagozlou M; Department of Immunology, Asthma and Allergy Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Sciences, Tehran, Iran., Movahedi M; Department of Immunology, Asthma and Allergy Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Sciences, Tehran, Iran., Ghadami M; Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran., Hamidieh AA; Hematology, Oncology and Stem Cell Transplantation Research Centre, Tehran University of Medical Sciences, Tehran, Iran., Azizi G; Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran., Yazdani R; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran; Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran., Afarideh M; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran., Ghajar A; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran., Havaei A; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran., Chavoshzadeh Z; Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Mahdaviani SA; Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran., Cheraghi T; Department of Pediatrics, 17th Shahrivar Children's Hospital, Guilan University of Medical Sciences, Rasht, Iran., Behniafard N; Department of Allergy and Clinical Immunology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran., Amin R; Department of Pediatric Immunology and Allergy, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran., Aleyasin S; Department of Pediatric Immunology and Allergy, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran., Faridhosseini R; Department of Allergy and Clinical Immunology, Mashhad University of Medical Sciences, Mashhad, Iran., Jabbari-Azad F; Department of Allergy and Clinical Immunology, Mashhad University of Medical Sciences, Mashhad, Iran., Nabavi M; Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Bemanian MH; Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Arshi S; Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Molatefi R; Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran; Department of Pediatrics, Bo-Ali children's Hospital of Ardabil University of Medical Sciences, Ardabil, Iran., Sherkat R; Acquired Immunodeficiency Research Center, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran., Mansouri M; Immunology and Allergy Department, Mofid Children's Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran., Mesdaghi M; Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Babaie D; Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Mohammadzadeh I; Noncommunicable Pediatric Diseases Research Center, Amirkola Hospital, Babol University of Medical Sciences, Babol, Iran., Ghaffari J; Department of Pediatrics, Mazandaran University of Medical Sciences, Sari, Iran., Shafiei A; Department of Immunology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran., Kalantari N; Department of Immunology and Allergy, Golestan University of Medical Sciences, Gorgan, Iran., Ahanchian H; Department of Allergy and Clinical Immunology, Mashhad University of Medical Sciences, Mashhad, Iran., Khoshkhui M; Department of Allergy and Clinical Immunology, Mashhad University of Medical Sciences, Mashhad, Iran., Soheili H; Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran., Dabbaghzadeh A; Noncommunicable Pediatric Diseases Research Center, Amirkola Hospital, Babol University of Medical Sciences, Babol, Iran., Shirkani A; Allergy and Clinical Immunology Department, Bushehr University of Medical Science, School of Medicine, Bushehr, Iran., Nasiri Kalmarzi R; Cellular & Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran., Mortazavi SH; Department of Pediatrics, Kermanshah University of Medical Sciences, Kermanshah, Iran., Tafaroji J; Department of Pediatrics, Qom University of Medical Sciences, Qom, Iran., Khalili A; Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran., Mohammadi J; Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran., Negahdari B; School of Advanced Technologies in Medicine, Department of Medical Biotechnology, Tehran University of Medical Sciences, Tehran, Iran., Joghataei MT; Cellular and Molecular Research Center & Department of Anatomy and Neuroscience, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Al-Ramadi BK; Department of Medical Microbiology & Immunology, College of Medicine and Health Sciences, United Arab University, Al-Ain, United Arab Emirates., Picard C; Study Center for Primary Immunodeficiencies, AP-HP, Necker Enfants Malades Hospital, Paris, France., Parvaneh N; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran., Rezaei N; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran; Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran., Chatila TA; Division of Immunology Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass., Massaad MJ; Division of Immunology Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass., Keles S; Division of Immunology Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass., Hammarström L; Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden., Geha RS; Division of Immunology Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address: raif.geha@childrens.harvard.edu., Aghamohammadi A; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran; Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran. Electronic address: aghamohammadi@tums.ac.ir.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2018 Apr; Vol. 141 (4), pp. 1450-1458. Date of Electronic Publication: 2017 Sep 12.
DOI: 10.1016/j.jaci.2017.06.049
Abstrakt: Background: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited.
Objectives: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically.
Methods: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients.
Results: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs.
Conclusions: This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.
(Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)
Databáze: MEDLINE
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