The impact of von Willebrand factor on factor VIII memory immune responses
被引:11
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作者:
Chen, Juan
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机构:
BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USABloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
Chen, Juan
[1
]
Schroeder, Jocelyn A.
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机构:
BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USABloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
Schroeder, Jocelyn A.
[1
,2
,3
]
Luo, Xiaofeng
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BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USABloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
Luo, Xiaofeng
[1
]
Shi, Qizhen
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机构:
BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USA
MACC Fund Res Ctr, Milwaukee, WI USABloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
Shi, Qizhen
[1
,2
,3
,4
]
机构:
[1] BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
[2] Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
[3] Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USA
Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis were used to study FVIII-primed CD4(+) T cells. When CD4(+) T cells from primed FVIIInull mice were restimulated with recombinant human FVIII (rhF8) plus recombinant human VWF (rhVWF) in vitro, the percentages of daughter CD4(+) T cells were significantly decreased compared with the groups cultured with rhF8 only. Levels of interferon-gamma and interleukin 10 were significantly lower in the rhF8 plus rhVWF groups than in the rhF8 groups. When memory B-cell pools from primed FVIIInull mice were cultured with rhF8 with or without rhVWF to induce differentiation of memory B cells into antibody-secreting cells (ASCs), the number of ASCs was significantly lower in the rhF8 plus VWF group than in the rhF8 group. When memory B-cell pools were transferred into NSGF8KO mice followed by rhF8 immunization with or without rhVWF, the titers of anti-F8 inhibitors and total immunoglobulin G were significantly higher in the rhF8 group than in the rhF8 plus rhVWF group, with an average difference of 2.23- and 2.04-fold. Together, our data demonstrate that VWF attenuates FVIII memory immune responses in HA mice.
机构:
Royal Free Hosp, Haemophilia Ctr, London NW3 2QG, England
Royal Free Hosp, Thrombosis Unit, London NW3 2QG, EnglandRoyal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, England
Huq, F. Y.
Kulkarni, A.
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Royal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, EnglandRoyal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, England
Kulkarni, A.
Bapir, M.
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机构:
Royal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, EnglandRoyal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, England
Bapir, M.
Egbam, E.
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机构:
Royal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, EnglandRoyal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, England
Egbam, E.
Tuddenham, E.
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机构:
Royal Free Hosp, Haemophilia Ctr, London NW3 2QG, England
Royal Free Hosp, Thrombosis Unit, London NW3 2QG, EnglandRoyal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, England
Tuddenham, E.
Kadir, R. A.
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机构:
Royal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, England
Royal Free Hosp, Haemophilia Ctr, London NW3 2QG, England
Royal Free Hosp, Thrombosis Unit, London NW3 2QG, EnglandRoyal Free Hosp, Dept Obstet & Gynaecol, London NW3 2QG, England
机构:
Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Univ Kansas, Med Ctr, Inst Reprod Med & Dev Sci, Kansas City, KS USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Cao, Wenjing
Trask, Aria R.
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机构:
Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Trask, Aria R.
Bignotti, Antonia I.
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机构:
Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Bignotti, Antonia I.
George, Lindsey A.
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机构:
Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
George, Lindsey A.
Doshi, Bhavya S.
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机构:
Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Doshi, Bhavya S.
Sabatino, Denise E.
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机构:
Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Sabatino, Denise E.
Yada, Noritaka
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Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Yada, Noritaka
Zheng, Liang
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机构:
Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Univ Kansas, Med Ctr, Inst Reprod Med & Dev Sci, Kansas City, KS USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Zheng, Liang
Camire, Rodney M.
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机构:
Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Camire, Rodney M.
Zheng, X. Long
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机构:
Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Univ Kansas, Med Ctr, Inst Reprod Med & Dev Sci, Kansas City, KS USA
Univ Kansas, Med Ctr, Dept Pathol & Lab Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USAUniv Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA