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Generation of two high affinity anti-mouse FcRn antibodies: Inhibition of IgG recycling in wild type mice and effect in a mouse model of immune thrombocytopenia.

Abstract：

:Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by pathogenic immunoglobulin G (IgG) autoantibodies that bind to platelets, causing their phagocytic removal and leading to reductions in platelet number. The neonatal Fc receptor (FcRn) selectively salvages and recycles IgG, including pathogenic IgG, thereby extending the half-life of IgG in plasma. Two anti-mouse FcRn monoclonal antibodies (mAb) (4470 and 4464) were generated to evaluate the effect of inhibiting IgG recycling. Statistically significant reductions in plasma IgG concentration were observed upon administration of 4470 (10, 30 and 100 mg/kg) in wild-type mice. In a passive mouse model of ITP, 4464 alleviated the reduction in platelet number and/or preserved newly produced platelets when dosed prophylactically as well as in a therapeutic dosing regimen once platelet numbers had already been reduced. These results support the investigation of anti-FcRn therapy as a potential treatment for ITP.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Smith B,Christodoulou L,Clargo A,Eddleston A,Greenslade K,Lightwood D,Shock A,Tyson K,Brennan FR

doi

10.1016/j.intimp.2018.11.040

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

362-365

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)31233-5

journal_volume

66

pub_type

杂志文章

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