New publication on complexes between drug and antidrug antibodies

Restricted immune activation and internalisation of anti-idiotype complexes between drug and antidrug antibodies

A new publication about therapeutic antibodies which can provoke antidrug antibody (ADA) responses has become available. It was a collaboration between with Sanquin (Amsterdam), LADCR (Leiden) and several groups within the LUMC. ADA formation events are rare, with notable exceptions, including infliximab. The in vitro formation and biological activities of ADA-drug anti-idiotype immune complexes using patient-derived monoclonal anti-infliximab antibodies were investigated. Soluble immune complexes with infliximab can be formed.

Size distribution and conformation of ADA-drug complexes were characterised by size-exclusion chromatography and electron microscopy. Internalisation of and immune activation by complexes was visualised with flow imaging, whole blood cell assay and C4b/c ELISA.

Size and conformation of immune complexes depended on the concentrations and ratio of drug and ADA. Large antibody complexes formed only with high ADA titres and these are efficiently internalised by macrophages, while only dimeric complexes showed up in circulation of patient sera.

ADA-drug complexes generally have limited immune activation capacity. Only very large complexes activated complement. Also antibody conformation influences actiavtion of effector functions, since anti-idiotype hexamers did not activate complement, unlike Fc-linked hexamers.


Restricted immune activation and internalisation of anti-idiotype complexes between drug and antidrug antibodiesvan Schie KA, Kruithof S, Ooijevaar-de Heer P, Derksen NIL, van de Bovenkamp FS, Saris A, Vidarsson G, Bentlage AEH, Jiskoot W, Romeijn S, Koning RI, Bos E, Stork EM, Koeleman CAM, Wuhrer M, Wolbink G, Rispens T. Ann Rheum Dis. 2018 Jun 26. pii: annrheumdis-2018-213299. doi: 10.1136/annrheumdis-2018-213299. [Epub ahead of print]

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