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Autoimmune Manifestations Among 461 Patients With Monogenic Inborn Errors of Immunity Publisher Pubmed



Azizi G1 ; Tavakol M1 ; Yazdani R2, 3 ; Delavari S2 ; Moeini Shad T2 ; Rasouli SE1 ; Jamee M1 ; Pashangzadeh S2 ; Kalantari A4 ; Shariat M5 ; Shafiei A6 ; Mohammadi J7 ; Hassanpour G8 ; Chavoshzadeh Z9 Show All Authors
Authors
  1. Azizi G1
  2. Tavakol M1
  3. Yazdani R2, 3
  4. Delavari S2
  5. Moeini Shad T2
  6. Rasouli SE1
  7. Jamee M1
  8. Pashangzadeh S2
  9. Kalantari A4
  10. Shariat M5
  11. Shafiei A6
  12. Mohammadi J7
  13. Hassanpour G8
  14. Chavoshzadeh Z9
  15. Mahdaviani SA10
  16. Momen T11
  17. Behniafard N12
  18. Nabavi M13
  19. Bemanian MH13
  20. Arshi S13
  21. Molatefi R14
  22. Sherkat R15
  23. Shirkani A16
  24. Alyasin S17
  25. Jabbariazad F18
  26. Ghaffari J19
  27. Mesdaghi M20
  28. Ahanchian H18
  29. Khoshkhui M18
  30. Eslamian MH21
  31. Cheraghi T22
  32. Dabbaghzadeh A23
  33. Nasiri Kalmarzi R24
  34. Esmaeilzadeh H17
  35. Tafaroji J25
  36. Khalili A26
  37. Sadeghishabestari M27
  38. Darougar S9
  39. Moghtaderi M17
  40. Ahmadiafshar A28
  41. Shakerian B29
  42. Heidarzadeh M30
  43. Ghalebaghi B22
  44. Fathi SM31
  45. Darabi B32
  46. Fallahpour M13
  47. Mohsenzadeh A33
  48. Ebrahimi S34
  49. Sharafian S9
  50. Vosughimotlagh A35
  51. Tafakoridelbari M34
  52. Rahimi Hajiabadi M34
  53. Ashournia P34
  54. Razaghian A34
  55. Rezaei A2
  56. Salami F2
  57. Shirmast P3
  58. Bazargan N36
  59. Mamishi S37
  60. Khazaei HA38
  61. Negahdari B39
  62. Shokri S13
  63. Nabavizadeh SH17
  64. Bazregari S40
  65. Ghasemi R29
  66. Bayat S41
  67. Eshaghi H36
  68. Rezaei N2
  69. Abolhassani H2, 42
  70. Aghamohammadi A2, 3

Source: Pediatric Allergy and Immunology Published:2021


Abstract

Background: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. Methods: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. Results: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. Conclusions: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease. © 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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