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Activated Phosphoinositide 3-Kinase Δ Syndrome: Update From the Esid Registry and Comparison With Other Autoimmune-Lymphoproliferative Inborn Errors of Immunity Publisher Pubmed



Maccari ME1, 2 ; Wolkewitz M3 ; Schwab C4 ; Lorenzini T1, 10 ; Leiding JW11 ; Aladjdi N12 ; Abolhassani H13, 14 ; Abouchahla W15 ; Aiuti A18, 19 ; Azarnoush S20 ; Baris S38, 39 ; Barlogis V42 ; Barzaghi F18 ; Baumann U44 Show All Authors
Authors
  1. Maccari ME1, 2
  2. Wolkewitz M3
  3. Schwab C4
  4. Lorenzini T1, 10
  5. Leiding JW11
  6. Aladjdi N12
  7. Abolhassani H13, 14
  8. Abouchahla W15
  9. Aiuti A18, 19
  10. Azarnoush S20
  11. Baris S38, 39
  12. Barlogis V42
  13. Barzaghi F18
  14. Baumann U44
  15. Bloomfield M48, 49
  16. Bohynikova N50
  17. Bodet D51
  18. Boutboul D21
  19. Bucciol G52, 53
  20. Buckland MS54, 55
  21. Burns SO56, 59
  22. Cancrini C60, 61
  23. Cathebras P62
  24. Cavazzana M22, 28, 37
  25. Cheminant M22, 29
  26. Chinello M65
  27. Ciznar P66
  28. Coulter TI67
  29. Daveni M68, 69
  30. Ekwall O70, 71
  31. Eric Z73
  32. Eren E74
  33. Fasth A70, 72
  34. Frange P23, 30
  35. Fournier B31
  36. Garciaprat M75
  37. Gardembas M76
  38. Geier C5
  39. Ghosh S78
  40. Goda V79
  41. Hammarstrom L13
  42. Hauck F80
  43. Heeg M1
  44. Heropolitanskapliszka E50
  45. Hilfanova A82
  46. Jolles S83
  47. Karakocaydiner E38, 39, 40
  48. Kindle GR1, 6
  49. Kiykim A41
  50. Klemann C45, 84
  51. Koletsi P85
  52. Koltan S86
  53. Kondratenko I87
  54. Korholz J89
  55. Kruger R90, 91
  56. Jeziorski E92, 93
  57. Levy R31
  58. Le Guenno G94
  59. Lefevre G16, 17
  60. Lougaris V10
  61. Marzollo A96
  62. Mahlaoui N31, 36
  63. Malphettes M21
  64. Meinhardt A97
  65. Merlin E95
  66. Meyts I52, 53
  67. Milota T48, 49
  68. Moreira F59
  69. Moshous D25, 31, 36
  70. Mukhina A88
  71. Neth O98
  72. Neubert J78
  73. Neven B24, 31
  74. Nieters A1, 6
  75. Novejosserand R99
  76. Oksenhendler E21
  77. Ozen A38, 39, 40
  78. Olbrich P98
  79. Perlat A100
  80. Pac M50
  81. Schmid JP101, 102
  82. Pacillo L60, 61
  83. Parramartinez A75
  84. Paschenko O87
  85. Pellier I77
  86. Sefer AP38, 39
  87. Plebani A10
  88. Plantaz D104
  89. Prader S101, 102
  90. Raffray L105, 106
  91. Ritterbusch H1
  92. Riviere JG75
  93. Rivalta B60, 61
  94. Rusch S1
  95. Sakovich I107
  96. Savic S108, 109
  97. Scheible R1, 81
  98. Schleinitz N43
  99. Schuetz C89
  100. Schulz A110
  101. Sediva A48, 49
  102. Semeraro M33, 34
  103. Sharapova SO107
  104. Shcherbina A88
  105. Slatter MA111, 112
  106. Sogkas G46, 47
  107. Solerpalacin P75
  108. Speckmann C1, 2
  109. Stephan JL63, 64
  110. Suarez F22, 29
  111. Tommasini A113, 114
  112. Truck J101, 102
  113. Uhlmann A1, 7
  114. Van Aerde KJ115
  115. Van Montfrans J116
  116. Von Bernuth H90, 91
  117. Warnatz K1, 5, 103
  118. Williams T74
  119. Worth AJJ58
  120. Ip W57, 58
  121. Picard C26, 31, 32, 36
  122. Catherinot E117
  123. Nademi Z111, 112
  124. Grimbacher B1, 5, 8, 9, 47
  125. Forbes Satter LR118, 119
  126. Kracker S27
  127. Chandra A120, 121
  128. Condliffe AM122
  129. Ehl S1

Source: Journal of Allergy and Clinical Immunology Published:2023


Abstract

Background: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS. Methods: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. Results: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. Conclusions: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients. © 2023 American Academy of Allergy, Asthma & Immunology
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