Sima Habibi1, Majid Zaki-Dizaji2, Hosein Rafiemanesh3, Bernice Lo4, Mahnaz Jamee5, Laura Gámez-Díaz6, Fereshte Salami1, Ali N Kamali7, Hamed Mohammadi8, Hassan Abolhassani9, Reza Yazdani1, Asghar Aghamohammadi1, Juan-Manuel Anaya10, Gholamreza Azizi11. 1. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 2. Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran. 3. Student Research Committee, Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Division of Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar. 5. Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran. 6. Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg im Breisgau, Germany. 7. CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran. 8. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 9. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. 10. Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia. 11. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. Electronic address: azizi@abzums.ac.ir.
Abstract
BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency and immune dysregulation syndrome caused by biallelic mutations in the LRBA gene. These mutations usually abrogate the protein expression of LRBA, leading to a broad spectrum of clinical phenotypes including autoimmunity, chronic diarrhea, hypogammaglobulinemia, and recurrent infections. OBJECTIVE: Our aim was to systematically collect all studies reporting on the clinical manifestations, molecular and laboratory findings, and management of patients with LRBA deficiency. METHODS: We searched in PubMed, Web of Science, and Scopus without any restrictions on study design and publication time. A total of 109 LRBA-deficient cases were identified from 45 eligible articles. For all patients, demographic information, clinical records, and immunologic and molecular data were collected. RESULTS: Of the patients with LRBA deficiency, 93 had homozygous and 16 had compound heterozygous mutations in LRBA. The most common clinical manifestations were autoimmunity (82%), enteropathy (63%), splenomegaly (57%), and pneumonia (49%). Reduction in numbers of CD4+ T cells and regulatory T cells as well as IgG levels was recorded for 21.6%, 65.6%, and 54.2% of evaluated patients, respectively. B-cell subpopulation analysis revealed low numbers of switched-memory and increased numbers of CD21low B cells in 73.5% and 77.8% of patients, respectively. Eighteen (16%) patients underwent hematopoietic stem cell transplantation due to the severity of complications and the outcomes improved in 13 of them. CONCLUSIONS: Autoimmune disorders are the main clinical manifestations of LRBA deficiency. Therefore, LRBA deficiency should be included in the list of monogenic autoimmune diseases, and screening for LRBA mutations should be routinely performed for patients with these conditions.
BACKGROUND:LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency and immune dysregulation syndrome caused by biallelic mutations in the LRBA gene. These mutations usually abrogate the protein expression of LRBA, leading to a broad spectrum of clinical phenotypes including autoimmunity, chronic diarrhea, hypogammaglobulinemia, and recurrent infections. OBJECTIVE: Our aim was to systematically collect all studies reporting on the clinical manifestations, molecular and laboratory findings, and management of patients with LRBA deficiency. METHODS: We searched in PubMed, Web of Science, and Scopus without any restrictions on study design and publication time. A total of 109 LRBA-deficient cases were identified from 45 eligible articles. For all patients, demographic information, clinical records, and immunologic and molecular data were collected. RESULTS: Of the patients with LRBA deficiency, 93 had homozygous and 16 had compound heterozygous mutations in LRBA. The most common clinical manifestations were autoimmunity (82%), enteropathy (63%), splenomegaly (57%), and pneumonia (49%). Reduction in numbers of CD4+ T cells and regulatory T cells as well as IgG levels was recorded for 21.6%, 65.6%, and 54.2% of evaluated patients, respectively. B-cell subpopulation analysis revealed low numbers of switched-memory and increased numbers of CD21low B cells in 73.5% and 77.8% of patients, respectively. Eighteen (16%) patients underwent hematopoietic stem cell transplantation due to the severity of complications and the outcomes improved in 13 of them. CONCLUSIONS:Autoimmune disorders are the main clinical manifestations of LRBA deficiency. Therefore, LRBA deficiency should be included in the list of monogenic autoimmune diseases, and screening for LRBA mutations should be routinely performed for patients with these conditions.
Authors: Swati Phalke; Katja Aviszus; Kira Rubtsova; Anatoly Rubtsov; Briana Barkes; Linda Powers; Brenda Warner; James L Crooks; John W Kappler; Evans R Fernández-Pérez; Lisa A Maier; Nabeel Hamzeh; Philippa Marrack Journal: Am J Respir Crit Care Med Date: 2020-10-01 Impact factor: 21.405
Authors: Sarah K Baxter; Tom Walsh; Silvia Casadei; Mary M Eckert; Eric J Allenspach; David Hagin; Gesmar Segundo; Ming K Lee; Suleyman Gulsuner; Brian H Shirts; Kathleen E Sullivan; Michael D Keller; Troy R Torgerson; Mary-Claire King Journal: J Allergy Clin Immunol Date: 2021-04-20 Impact factor: 10.793
Authors: M Jamee; S Hosseinzadeh; N Sharifinejad; M Zaki-Dizaji; M Matloubi; M Hasani; S Baris; M Alsabbagh; B Lo; G Azizi Journal: Clin Exp Immunol Date: 2021-05-03 Impact factor: 5.732