Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients.

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Keywords :

Adult; Antigen-Antibody Complex/genetics/immunology; Blood Platelets/drug effects/immunology; Crohn Disease/blood/drug therapy/genetics/immunology; Endothelial Cells/drug effects/immunology; Female; Flow Cytometry; Humans; Immunoglobulin G/genetics/immunology; Infliximab/administration & dosage/pharmacokinetics; Male; Platelet Activation/drug effects; Platelet Count; Polymorphism, Genetic/genetics; Receptors, IgG/genetics; FcγRIIA; Fc–Fc receptor interaction; IgG subclasses; clearance; immunotherapy; monoclonal antibodies; platelets; polymorphism

Abstract :

[en] The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn's disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 10(9)/L, respectively, to ≈13 days (both HR and RR) at 350 × 10(9)/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.

Disciplines :

Gastroenterology & hepatology

Author, co-author :

Thibault, Gilles

Paintaud, Gilles

Sung, Hsueh Cheng

Lajoie, Laurie

Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie

The Getaid

Desvignes, Celine

Watier, Hervé

Gouilleux-Gruart, Valérie

Ternant, David

Language :

English

Title :

Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients.

Publication date :

2021

Journal title :

International Journal of Molecular Sciences

ISSN :

1661-6596

eISSN :

1422-0067

Publisher :

Multidisciplinary Digital Publishing Institute (MDPI), Switzerland

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://doi.org/10.3390/ijms22116051

Commentary :

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Available on ORBi :

since 15 December 2021

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