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Monogenic Primary Immunodeficiency Disorder Associated With Common Variable Immunodeficiency and Autoimmunity Publisher Pubmed



Asgardoon MH1 ; Azizi G2 ; Yazdani R1, 3 ; Sohani M1 ; Pashangzadeh S1 ; Kalantari A4 ; Shariat M5 ; Shafiei A6 ; Salami F1 ; Jamee M2 ; Rasouli SE2 ; Mohammadi J7 ; Hassanpour G8 ; Tavakol M2 Show All Authors
Authors
  1. Asgardoon MH1
  2. Azizi G2
  3. Yazdani R1, 3
  4. Sohani M1
  5. Pashangzadeh S1
  6. Kalantari A4
  7. Shariat M5
  8. Shafiei A6
  9. Salami F1
  10. Jamee M2
  11. Rasouli SE2
  12. Mohammadi J7
  13. Hassanpour G8
  14. Tavakol M2
  15. Chavoshzadeh Z9
  16. Mahdaviani SA10
  17. Momen T11
  18. Behniafard N12
  19. Nabavi M13
  20. Bemanian MH13
  21. Arshi S13
  22. Molatefi R14
  23. Sherkat R15
  24. Shirkani A16
  25. Alyasin S17
  26. Jabbariazad F18
  27. Ghaffari J19
  28. Mesdaghi M20
  29. Ahanchian H18
  30. Khoshkhui M18
  31. Eslamian MH21
  32. Cheraghi T22
  33. Dabbaghzadeh A23
  34. Nasiri Kalmarzi R24
  35. Esmaeilzadeh H17
  36. Tafaroji J25
  37. Khalili A26
  38. Sadeghishabestari M27
  39. Darougar S9
  40. Moghtaderi M17
  41. Ahmadiafshar A28
  42. Shakerian B29
  43. Heidarzadeh M30
  44. Ghalebaghi B22
  45. Fathi SM31
  46. Darabi B32
  47. Fallahpour M13
  48. Mohsenzadeh A33
  49. Ebrahimi S34
  50. Sharafian S34
  51. Vosughimotlagh A34
  52. Tafakoridelbari M34
  53. Rahimi Hajiabadi M34
  54. Ashournia P34
  55. Razaghian A34
  56. Rezaei A1
  57. Delavari S1
  58. Shirmast P1
  59. Babaha F1
  60. Samavat A35
  61. Mamishi S36
  62. Khazaei HA37
  63. Negahdari B38
  64. Rezaei N1
  65. Abolhassani H3, 39, 40
  66. Aghamohammadi A1, 3
Show Affiliations
Authors Affiliations
  1. 1. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, 62 Qarib St., Keshavarz Blvd., Tehran, 14194, Iran
  2. 2. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  3. 3. Iranian Primary Immunodeficiencies Network (IPIN), Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Immunology and Allergy, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Allergy and Clinical Immunology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Immunology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Life Science, Faculty of New Science and Technology, University of Tehran, Tehran, Iran
  8. 8. Center for Research of Endemic Parasites of Iran, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  10. 10. Pediatric Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
  11. 11. Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  12. 12. Department of Allergy and Clinical Immunology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  13. 13. Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
  14. 14. Department of Pediatrics, Bo-Ali Children's Hospital of Ardabil University of Medical Sciences, Ardabil, Iran
  15. 15. Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  16. 16. Allergy and Clinical Immunology Department, Bushehr University of Medical Sciences, School of Medicine, Bushehr, Iran
  17. 17. Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  18. 18. Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  19. 19. Department of Pediatrics, Mazandaran University of Medical Sciences, Sari, Iran
  20. 20. Immunology and Allergy Department, Mofid Children's Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
  21. 21. Department of Pediatrics, Hamedan University of Medical Sciences, Hamedan, Iran
  22. 22. Department of Pediatrics, 17 Shahrivar Children's Hospital, Guilan University of Medical Sciences, Rasht, Iran
  23. 23. Department of Allergy and Clinical Immunology, Pediatrics Infectious Diseases Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  24. 24. Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
  25. 25. Department of Pediatrics, Qom University of Medical Sciences, Qom, Iran
  26. 26. Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  27. 27. Department of Immunology and Allergy, Tabriz University of Medical Sciences, Tabriz, Iran
  28. 28. Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
  29. 29. Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  30. 30. Department of Immunology and Allergy, Kashan University of Medical Sciences, Kashan, Iran
  31. 31. Department of Immunology and Allergy, Qazvin University of Medical Sciences, Qazvin, Iran
  32. 32. Department of Immunology and Allergy, Ilam University of Medical Sciences, Ilam, Iran
  33. 33. Department of Pediatrics, Lorestan University of Medical Sciences, Khorramabad, Iran
  34. 34. Division of Allergy and Clinical Immunology, Department of Pediatrics, Pediatrics Center of Excellences, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  35. 35. Genetics Office, Centers for Disease Control and Prevention (CDC), Ministry of Health of Iran, Tehran, Iran
  36. 36. Pediatric Infectious Diseases Research Center, Tehran University of Medical, Sciences, Tehran, Iran
  37. 37. Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
  38. 38. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  39. 39. Research Center for Primary Immunodeficiency, Iran University of Medical Sciences, Tehran, Iran
  40. 40. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden

Source: International Archives of Allergy and Immunology Published:2020


Abstract

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity. © 2020 S. Karger AG, Basel. All rights reserved.
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