PT - JOURNAL ARTICLE AU - Haizhang Chen AU - Andrea Maul-Pavicic AU - Martin Holzer AU - Ulrich Salzer AU - Nina Chevalier AU - Reinhard E. Voll AU - Hartmut Hengel AU - Philipp Kolb TI - FcγR responses to soluble immune complexes of varying size: A scalable cell-based reporter system AID - 10.1101/2020.11.11.378232 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.11.11.378232 4099 - http://biorxiv.org/content/early/2020/11/16/2020.11.11.378232.short 4100 - http://biorxiv.org/content/early/2020/11/16/2020.11.11.378232.full 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.