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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/9035

Title: Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange
Authors: Kolfschoten, Marijn van der Neut
Schuurman, Janine
Losen, Mario
Bleeker, Wim K.
Martinez-Martinez, Pilar
den Bleker, Tamara H.
Wiegman, Luus
Vink, Tom
Aarden, Lucien A.
De Baets, Marc H.
van De Winkel, Jan G. J.
Aalberse, Rob C.
Parren, Paul W. H. I.
Issue Date: 2007
Citation: SCIENCE, 317(5844). p. 1554-1557
Abstract: Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half-molecule) with a heavy-light chain pair from another molecule, which results in bispecific antibodies. Mutagenesis studies revealed that the third constant domain is critical for this activity. The impact of IgG4 Fab arm exchange was confirmed in vivo in a rhesus monkey model with experimental autoimmune myasthenia gravis. IgG4 Fab arm exchange is suggested to be an important biological mechanism that provides the basis for the anti-inflammatory activity attributed to IgG4 antibodies.
Notes: Genmab, NL-3584 CM Utrecht, Netherlands. Sanquin Res, AMC Landsteiner Lab, Dept Immunopathol, NL-1066 CX Amsterdam, Netherlands. Univ Maastricht, Dept Neurosci, Inst Mental Hlth & Neurosci, Maastricht, Netherlands. Hasselt Univ, Neuroimmunol Grp, Biomed Res Inst, Diepenbeek, Belgium. Univ Med Ctr, Dept Immunol, Immunotherapy Lab, Utrecht, Netherlands.
URI: http://hdl.handle.net/1942/9035
ISI #: 000249467900043
ISSN: 0036-8075
Category: A1
Type: Journal Contribution
Validation: ecoom, 2008
Appears in Collections: Research publications

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