Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Abstract:

:Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Graeter S,Schneider C,Verschoor D,von Däniken S,Seibold F,Yawalkar N,Villiger P,Dimitrov JD,Smith DF,Cummings RD,Simon HU,Vassilev T,von Gunten S

doi

10.3389/fimmu.2020.00973

subject

Has Abstract

pub_date

2020-05-19 00:00:00

pages

973

issn

1664-3224

journal_volume

11

pub_type

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