von Willebrand factor neutralizing and non-neutralizing alloantibodies in 213 subjects with type 3 von Willebrand disease enrolled in 3WINTERS-IPS

被引：8

作者：

Pagliari, Maria Teresa ^{[1
]}

Budde, Ulrich ^{[2
]}

Baronciani, Luciano ^{[1
]}

Eshghi, Peyman ^{[3
]}

Ahmadinejad, Minoo ^{[3
,4
]}

Badiee, Zahra ^{[5
]}

Baghaipour, Mohammad-Reza ^{[6
]}

Hidalgo, Olga Benitez ^{[7
]}

Biguzzi, Eugenia ^{[1
]}

Bodo, Imre ^{[8
]}

Castaman, Giancarlo ^{[9
]}

Goudemand, Jenny ^{[10
]}

Karimi, Mehran ^{[11
]}

Keikhaei, Bijan ^{[12
]}

Lassila, Riitta ^{[13
]}

Leebeek, Frank W. G. ^{[14
]}

Fernandez, Maria Fernanda Lopez ^{[15
]}

Marino, Renato ^{[16
]}

Oldenburg, Johannes ^{[17
]}

Peake, Ian ^{[18
]}

Santoro, Cristina ^{[19
]}

Schneppenheim, Reinhard ^{[20
]}

Tiede, Andreas ^{[21
]}

Toogeh, Gholamreza ^{[22
]}

Tosetto, Alberto ^{[23
]}

Trossaert, Marc ^{[24
]}

Yadegari, Hamideh ^{[17
]}

Zetterberg, Eva M. K. ^{[25
]}

Mannucci, Pier Mannuccio ^{[1
]}

Federici, Augusto B. ^{[26
]}

Eikenboom, Jeroen ^{[27
]}

Peyvandi, Flora ^{[1
,28
,29
,30
]}

机构：

[1] Fdn IRCCS CaGranda Osped Maggiore Policlin, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy

[2] Hemostaseol Medilys Laborgesellschaft mbH, Hamburg, Germany

[3] Shahid Beheshti Univ Med Sci, Pediat Congenital Hematol Disorders Res Ctr, Tehran, Iran

[4] High Inst Res & Educ Transfus Med, Blood Transfus Res Ctr, Tehran, Iran

[5] Mashhad Univ Med Sci, Hemophilia Thalassemia Ctr, Mashhad, Iran

[6] Iranian Hemophilia Comprehens Treatment Ctr, Tehran, Iran

[7] Hosp Univ Vall dHebron, Hematol Dept, Hemophilia Unit, Barcelona, Spain

[8] Hematol Semmelweis Univ, Dept Internal Med, Budapest, Hungary

[9] Careggi Univ Hosp, Ctr Bleeding Disorders & Coagulat, Florence, Italy

[10] Univ Lille, Dept Hematol & Transfus, CHU Lille, Lille, France

[11] Shiraz Univ Med Sci, Nemazee Hosp, Hematol Res Ctr, Shiraz, Iran

[12] Ahvaz Jundishapur Univ Med Sci, Hlth Res Inst, Thalassemia & Hemoglobinopathy Res Ctr, Ahvaz, Iran

[13] Univ Helsinki, Helsinki Univ Cent Hosp, Res Program Unit Oncol, Coagulat Disorders, Helsinki, Finland

[14] Univ Med Ctr Rotterdam, Dept Hematol, Erasmus MC, Rotterdam, Netherlands

[15] Complejo Hosp Univ A Coruna, Serv Hematol & Hemoterapia, La Coruna, Spain

[16] Univ Hosp Policlin, Hemophilia & Thrombosis Ctr, Bari, Italy

[17] Univ Hosp Bonn, Inst Expt Haematol & Transfus Med, Bonn, Germany

[18] Univ Sheffield, Fac Med Dent & Hlth, Sheffield, England

[19] Univ Hosp Policlin Umberto I, Hematol Hemophilia & Thrombosis Ctr, Rome, Italy

[20] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[21] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany

[22] Univ Tehran Med Sci, Thrombosis Hemostasis Res Ctr, Tehran, Iran

[23] San Bortolo Hosp, Hemophilia & Thrombosis Ctr, Hematol Dept, Vicenza, Italy

[24] Ctr Reg Traitement lHemophilie, Lab dHematol, Nantes, France

[25] Skane Univ Hosp, Malmo, Sweden

[26] Univ Milan, L Sacco Univ Hosp, Dept Oncol & Oncohematol Hematol & Transfus Med, Milan, Italy

[27] Leiden Univ Med Ctr, Dept Internal Med, Div Thrombosis & Hemostasis, Leiden, Netherlands

[28] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy

[29] Fdn IRCCS CaGranda Osped Maggiore Policlin, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy

[30] Univ Milan, Dept Pathophysiol & Transplantat, Via Pace, I-20122 Milan, Italy

来源：

JOURNAL OF THROMBOSIS AND HAEMOSTASIS | 2023年 / 21卷 / 04期

关键词：

anaphylaxis; antibodies neutralizing; diagnosis; von Willebrand disease; von Willebrand factor; PRECIPITATING ANTIBODIES; QUANTITATIVE-ANALYSIS; FACTOR PROPEPTIDE; GENE; VWF; PATHOPHYSIOLOGY; CLASSIFICATION; GUIDELINES; MANAGEMENT; DIAGNOSIS;

D O I：

10.1016/j.jtha.2023.01.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 al-loantibodies 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), ho-mozygous 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 epi-topes, their detection is dependent on the assay used.

引用

页码：787 / 799

页数：13

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