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Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort Publisher Pubmed



Yazdani R1, 2 ; Abolhassani H1, 2, 3 ; Kiaee F1, 2 ; Habibi S1, 2 ; Azizi G4 ; Tavakol M4 ; Chavoshzadeh Z5 ; Mahdaviani SA6 ; Momen T7 ; Gharagozlou M8 ; Movahedi M8 ; Hamidieh AA9 ; Behniafard N10 ; Nabavi M11 Show All Authors
Authors
  1. Yazdani R1, 2
  2. Abolhassani H1, 2, 3
  3. Kiaee F1, 2
  4. Habibi S1, 2
  5. Azizi G4
  6. Tavakol M4
  7. Chavoshzadeh Z5
  8. Mahdaviani SA6
  9. Momen T7
  10. Gharagozlou M8
  11. Movahedi M8
  12. Hamidieh AA9
  13. Behniafard N10
  14. Nabavi M11
  15. Bemanian MH11
  16. Arshi S11
  17. Molatefi R12
  18. Sherkat R13
  19. Shirkani A14
  20. Amin R15
  21. Aleyasin S15
  22. Faridhosseini R16
  23. Jabbariazad F16
  24. Mohammadzadeh I17
  25. Ghaffari J18
  26. Shafiei A19
  27. Kalantari A20
  28. Mansouri M21
  29. Mesdaghi M21
  30. Babaie D4
  31. Ahanchian H16
  32. Khoshkhui M16
  33. Soheili H22
  34. Eslamian MH23
  35. Cheraghi T24
  36. Dabbaghzadeh A17
  37. Tavassoli M25
  38. Kalmarzi RN26
  39. Mortazavi SH27
  40. Kashef S15
  41. Esmaeilzadeh H15
  42. Tafaroji J28
  43. Khalili A29
  44. Zandieh F19
  45. Sadeghishabestari M30
  46. Darougar S5
  47. Behmanesh F15
  48. Akbari H15
  49. Zandkarimi M16
  50. Abolnezhadian F31
  51. Fayezi A32
  52. Moghtaderi M15
  53. Ahmadiafshar A32
  54. Shakerian B25
  55. Sajedi V33
  56. Taghvaei B34
  57. Safari M23
  58. Heidarzadeh M35
  59. Ghalebaghi B24
  60. Fathi SM36
  61. Darabi B37
  62. Bazregari S14
  63. Bazargan N38
  64. Fallahpour M11
  65. Khayatzadeh A39
  66. Javahertrash N11
  67. Bashardoust B5
  68. Zamani M40
  69. Mohsenzadeh A41
  70. Ebrahimi S8
  71. Sharafian S8
  72. Vosughimotlagh A8
  73. Tafakoridelbari M8
  74. Rahim M8
  75. Ashournia P8
  76. Razaghian A8
  77. Rezaei A1, 2
  78. Samavat A42
  79. Mamishi S43
  80. Khazaei HA44
  81. Mohammadi J45
  82. Negahdari B46
  83. Parvaneh N1, 2
  84. Rezaei N1, 2
  85. Lougaris V47
  86. Giliani S48
  87. Plebani A47
  88. Ochs HD49
  89. Hammarstrom L3
  90. Aghamohammadi A1, 2
Show Affiliations
Authors Affiliations
  1. 1. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Iranian Primary Immunodeficiencies Network (IPIN), Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
  4. 4. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, 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 (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  8. 8. Division of Allergy and Clinical Immunology, Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Hematology, Oncology and Stem Cell Transplantation Research Centre, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Department of Allergy and Clinical Immunology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  11. 11. Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
  12. 12. Department of Pediatrics, Bo-Ali Children's Hospital of Ardabil University of Medical Sciences, Ardabil, Iran
  13. 13. Acquired Immunodeficiency Research Center, lsfahan University of Medical Sciences, Isfahan, Iran
  14. 14. Allergy and Clinical Immunology Department, Bushehr University of Medical Science, School of Medicine, Bushehr, Iran
  15. 15. Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  16. 16. Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  17. 17. Department of Allergy and Clinical Immunology, Pediatric Infectious Diseases Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  18. 18. Department of Pediatrics, Mazandaran University of Medical Sciences, Sari, Iran
  19. 19. Department of Immunology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
  20. 20. Department of Immunology and Allergy, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
  21. 21. Immunology and Allergy Department, Mofid Children's Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
  22. 22. Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran
  23. 23. Department of Pediatrics, Hamadan University of Medical Sciences, Hamadan, Iran
  24. 24. Department of Pediatrics, 17th Shahrivar Children's Hospital, Guilan University of Medical Sciences, Rasht, Iran
  25. 25. Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  26. 26. Cellular & Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
  27. 27. Department of Pediatrics, Kermanshah University of Medical Sciences, Kermanshah, Iran
  28. 28. Department of Pediatrics, Qom University of Medical Sciences, Qom, Iran
  29. 29. Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  30. 30. Department of Immunology and Allergy, Tabriz University of Medical Sciences, Tabriz, Iran
  31. 31. Department of Immunology and Allergy, Ahvaz University of Medical Sciences, Ahvaz, Iran
  32. 32. Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
  33. 33. Department of Immunology and Allergy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  34. 34. Department of Immunology and Allergy, Semnan University of Medical Sciences, Semnan, Iran
  35. 35. Department of Immunology and Allergy, Kashan University of Medical Sciences, Kashan, Iran
  36. 36. Department of Immunology and Allergy, Qazvin University of Medical Sciences, Qazvin, Iran
  37. 37. Department of Immunology and Allergy, Ilam University of Medical Sciences, Ilam, Iran
  38. 38. Department of Immunology and Allergy, Kerman University of Medical Sciences, Kerman, Iran
  39. 39. Department of Allergy and Clinical Immunology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  40. 40. Department of Immunology and Allergy, Shahrekord University of Medical Sciences, Shahrekord, Iran
  41. 41. Department of Pediatrics, Lorestan University of Medical Sciences, Khorramabad, Iran
  42. 42. Genetics Office, Centers for Disease Control and Prevention (CDC), Ministry of Health of Iran, Tehran, Iran
  43. 43. Pediatric Infectious Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
  44. 44. Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
  45. 45. Department of Life Science, Faculty of New Science and Technology, University of Tehran, Tehran, Iran
  46. 46. School of Advanced Technologies in Medicine, Department of Medical Biotechnology, Tehran University of Medical Sciences, Tehran, Iran
  47. 47. Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
  48. 48. Nocivelli Institute for Molecular Medicine and Pediatric Clinic, University of Brescia, Brescia, Italy
  49. 49. Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, Wash, United States

Source: Journal of Allergy and Clinical Immunology: In Practice Published:2019


Abstract

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment. © 2018 American Academy of Allergy, Asthma & Immunology
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