Gholamreza Azizi1,2,3, Hassan Abolhassani2,3,4, Seyed Alireza Mahdaviani5, Zahra Chavoshzadeh6, Peyman Eshghi7, Reza Yazdani2,8, Fatemeh Kiaee2,3, Mohammadreza Shaghaghi2,9, Javad Mohammadi10, Nima Rezaei2,9, Lennart Hammarström4, Asghar Aghamohammadi2,3. 1. Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran. 2. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 4. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. 5. Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 6. Pediatric Infections Research Center, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 7. Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8. Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 9. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 10. Department of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran.
Abstract
BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity, and enteropathy. METHODS: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. For all patients, demographic information, clinical records, laboratory, and molecular data were collected. RESULT: Hypogammaglobulinemia was reported in 14 (82.4%), CD4+ T-cell deficiency in five (29.4%), NK cell deficiency in three (21.4%), and CD19+ B-cell deficiency in 11 (64.7%) patients. All patients had history of infectious complications; pneumonia was the most common (76.5%) occurring infection. A history of lymphoproliferative disorders was observed in 14 (82.3%), enteropathy in 13 (76.5%), allergic symptoms in six (35.5%), neurologic problems in four (23.5), and autoimmunity (mostly autoimmune cytopenia) in 13 (76.5%) patients. Sirolimus treatment improved enteropathy of patients with remarkable success. The 20-year overall survival rate declined to 70.6%. CONCLUSION: LRBA deficiency has a very broad and variable phenotype and should be considered, especially in children with early-onset hypogammaglobulinemia, severe autoimmune manifestations, enteropathy, lymphoproliferation, and recurrent respiratory tract infections.
BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity, and enteropathy. METHODS: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. For all patients, demographic information, clinical records, laboratory, and molecular data were collected. RESULT: Hypogammaglobulinemia was reported in 14 (82.4%), CD4+ T-cell deficiency in five (29.4%), NK cell deficiency in three (21.4%), and CD19+ B-cell deficiency in 11 (64.7%) patients. All patients had history of infectious complications; pneumonia was the most common (76.5%) occurring infection. A history of lymphoproliferative disorders was observed in 14 (82.3%), enteropathy in 13 (76.5%), allergic symptoms in six (35.5%), neurologic problems in four (23.5), and autoimmunity (mostly autoimmune cytopenia) in 13 (76.5%) patients. Sirolimus treatment improved enteropathy of patients with remarkable success. The 20-year overall survival rate declined to 70.6%. CONCLUSION:LRBA deficiency has a very broad and variable phenotype and should be considered, especially in children with early-onset hypogammaglobulinemia, severe autoimmune manifestations, enteropathy, lymphoproliferation, and recurrent respiratory tract infections.
Authors: Svetlana O Sharapova; Emma Haapaniemi; Inga S Sakovich; Jessica Rojas; Laura Gámez-Díaz; Yuliya E Mareika; Irina E Guryanova; Alexandr A Migas; Taisiya M Mikhaleuskaya; Bodo Grimbacher; Olga V Aleinikova Journal: J Clin Immunol Date: 2018-05-26 Impact factor: 8.317