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The Autoimmune Manifestations in Patients With Genetic Defects in the B Cell Development and Differentiation Stages Publisher Pubmed



Azizi G1, 2 ; Hesari MF1 ; Sharifinejad N1 ; Fayyaz F3, 4 ; Chavoshzadeh Z5 ; Mahdaviani SA6 ; Alan MS7 ; Jamee M8 ; Tavakol M1 ; Sadri H1 ; Shahrestanaki E1, 9 ; Nabavi M10 ; Ebrahimi SS11 ; Shirkani A12 Show All Authors
Authors
  1. Azizi G1, 2
  2. Hesari MF1
  3. Sharifinejad N1
  4. Fayyaz F3, 4
  5. Chavoshzadeh Z5
  6. Mahdaviani SA6
  7. Alan MS7
  8. Jamee M8
  9. Tavakol M1
  10. Sadri H1
  11. Shahrestanaki E1, 9
  12. Nabavi M10
  13. Ebrahimi SS11
  14. Shirkani A12
  15. Vosughi Motlagh A13
  16. Delavari S2
  17. Rasouli SE1
  18. Esmaeili M2
  19. Salami F2
  20. Yazdani R2, 14
  21. Rezaei N2, 4, 15
  22. Abolhassani H2, 16
Show Affiliations
Authors Affiliations
  1. 1. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  2. 2. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  5. 5. Pediatric Infections Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6. Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
  8. 8. Pediatric Nephrology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  9. 9. Department of Epidemiology, School of Public Health, Iran University of Medical Science, Tehran, Iran
  10. 10. Department of Allergy and Clinical Immunology, Rasool E Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
  11. 11. Department of Immunology and Allergy, Kerman University of Medical Sciences, Kerman, Iran
  12. 12. Allergy and Clinical Immunology Department, School of Medicine, Bushehr University of Medical Science, Moallem St, Bushehr, Iran
  13. 13. Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd, Iran
  14. 14. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States
  15. 15. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  16. 16. Division of Clinical Immunology, Department of Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital, NEO, Blickagangen 16, Huddinge, Stockholm, 14157, Sweden

Source: Journal of Clinical Immunology Published:2023


Abstract

Purpose: Primary B cell defects manifesting as predominantly antibody deficiencies result from variable inborn errors of the B cell lineage and their development, including impairments in early bone marrow development, class switch recombination (CSR), or terminal B cell differentiation. In this study, we aimed to investigate autoimmunity in monogenic patients with B cell development and differentiation defects. Methods: Patients with known genetic defects in the B cell development and differentiation were recruited from the Iranian inborn errors of immunity registry. Results: A total of 393 patients with a known genetic defect in the B cell development and differentiation (257 males; 65.4%) with a median age of 12 (6–20) years were enrolled in this study. After categorizing patients, 109 patients had intrinsic B cell defects. More than half of the patients had defects in one of the ATM (85 patients), BTK (76 patients), LRBA (34 patients), and DOCK8 (33 patients) genes. Fifteen patients (3.8%) showed autoimmune complications as their first manifestation. During the course of the disease, autoimmunity was reported in 81 (20.6%) patients at a median age of 4 (2–7) years, among which 65 patients had mixed intrinsic and extrinsic and 16 had intrinsic B cell defects. The comparison between patients with the mentioned four main gene defects showed that the patient group with LRBA defect had a significantly higher frequency of autoimmunity compared to those with other gene defects. Based on the B cell defect stage, 13% of patients with early B cell defect, 17% of patients with CSR defect, and 40% of patients who had terminal B cell defect presented at least one type of autoimmunity. Conclusion: Our results demonstrated that gene mutations involved in human B cell terminal stage development mainly LRBA gene defect have the highest association with autoimmunity. © 2023, The Author(s).
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