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Von Willebrand Factor Neutralizing and Non-Neutralizing Alloantibodies in 213 Subjects With Type 3 Von Willebrand Disease Enrolled in 3Winters-Ips Publisher Pubmed



Pagliari MT1 ; Budde U2 ; Baronciani L1 ; Eshghi P3 ; Ahmadinejad M3, 4 ; Badiee Z5 ; Baghaipour MR6 ; Hidalgo OB7 ; Biguzzi E1 ; Bodo I8 ; Castaman G9 ; Goudemand J10 ; Karimi M11 ; Keikhaei B12 Show All Authors
Authors
  1. Pagliari MT1
  2. Budde U2
  3. Baronciani L1
  4. Eshghi P3
  5. Ahmadinejad M3, 4
  6. Badiee Z5
  7. Baghaipour MR6
  8. Hidalgo OB7
  9. Biguzzi E1
  10. Bodo I8
  11. Castaman G9
  12. Goudemand J10
  13. Karimi M11
  14. Keikhaei B12
  15. Lassila R13
  16. Leebeek FWG14
  17. Lopez Fernandez MF15
  18. Marino R16
  19. Oldenburg J17
  20. Peake I18
  21. Santoro C19
  22. Schneppenheim R20
  23. Tiede A21
  24. Toogeh G22
  25. Tosetto A23
  26. Trossaert M24
  27. Yadegari H17
  28. Zetterberg EMK25
  29. Mannucci PM1
  30. Federici AB26
  31. Eikenboom J27
  32. Peyvandi F1, 28

Source: Journal of Thrombosis and Haemostasis Published:2023


Abstract

Background: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions. Objective: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS. Methods: An indirect in-house enzyme-linked immunosorbent assay has been used to test all the alloantibodies against VWF. Neutralizing antibodies (inhibitors) have been tested with a Bethesda-based method by using a VWF collagen binding (VWF:CB) assay. Samples positive for anti-VWF antibodies were further tested with Bethesda-based methods by using the semiautomated gain-of-function glycoprotein-Ib binding (VWF:GPIbM) and a VWF antigen (VWF:Ag) enzyme-linked immunosorbent assay. Results: In total, 18 of the 213 (8.4%) subjects tested positive for anti-VWF antibodies and 13 of 213 (6%) had VWF:CB inhibitors. These 13 were among the 18 with anti-VWF antibodies. Of the 5 without VWF:CB inhibitors, 3 had non-neutralizing antibodies, 1 only inhibitor against VWF:GPIbM, and one could not be tested further. Ten of the 13 subjects with VWF:CB inhibitors also had VWF:GPIbM inhibitors, 6 of whom also had VWF:Ag inhibitors. Subjects with inhibitors were homozygous for VWF null alleles (11/14), homozygous for a missense variant (1/14), or partially characterized (2/14). Conclusions: Anti-VWF antibodies were found in 8.4% of subjects with type 3 VWD, whereas neutralizing VWF inhibitors were found in 6%, mainly in subjects homozygous for VWF null alleles. Because inhibitors may be directed toward different VWF epitopes, their detection is dependent on the assay used. © 2023 International Society on Thrombosis and Haemostasis