RT Journal Article
SR Electronic
T1 FcγR responses to soluble immune complexes of varying size: A scalable cell-based reporter system
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.11.378232
DO 10.1101/2020.11.11.378232
A1 Haizhang Chen
A1 Andrea Maul-Pavicic
A1 Martin Holzer
A1 Ulrich Salzer
A1 Nina Chevalier
A1 Reinhard E. Voll
A1 Hartmut Hengel
A1 Philipp Kolb
YR 2020
UL http://biorxiv.org/content/early/2020/11/16/2020.11.11.378232.abstract
AB Fcγ-receptor (FcγR) activation by antibody derived soluble immune complexes (sICs) is a major contributor to inflammation in autoimmune diseases such as systemic lupus erythematosus (SLE). A robust and scalable test system allowing for the detection and quantification of sICs with regard to receptor activation is missing. We developed a comprehensive cell-based reporter system capable of measuring the sIC-mediated activation of human and mouse FcγRs individually. We show that compared to human FcγRs IIB and III, human FcγRs I and IIA lack sensitivity to sICs. The assay enables measurement of FcγR activation in response to sIC size and demonstrates a complete translation of the Heidelberger-Kendall precipitation curve to FcγR responsiveness. The assay also proved useful to quantify sICs-mediated FcγR activation using sera from SLE patients and mouse models of lupus and arthritis. Thus, in clinical practice, our assay might be employed as a diagnostic tool to measure FcγR activation as a biomarker for disease activity in immune-complex mediated disease.Competing Interest StatementThe authors have declared no competing interest.