Abstract
Fcγ-receptor (FcγR) activation by antibody formed soluble immune complexes (sICs) is thought to be a major mechanism of inflammation in certain autoimmune diseases such as systemic lupus erythematosus (SLE). A robust and scalable test system allowing for the detection and quantification of sICs bioactivity is missing. We developed a comprehensive reporter cell panel capable of measuring the sIC-mediated activation of individual human and mouse FcγRs. We show that compared to human FcγRs IIB and III, human FcγRs I and IIA lack sensitivity to sICs. Further, the assay proved to be sensitive to sIC stoichiometry and size enabling us to demonstrate for the first time a complete translation of the Heidelberger-Kendall precipitation curve to FcγR responsiveness. The approach was applied to quantify sICs-mediated FcγR activation using sera from SLE patients and mouse models of lupus and arthritis. Thus, in clinical practice, it might be employed as a test matrix toolbox for FcγR activation evaluating sICs as a biomarker for disease activity in immune-complex mediated diseases.
Summary This study describes a novel cell-based reporter assay enabling the detection and quantification of soluble multimeric IgG immune complexes (sICs). Receptor triggering of sICs is restricted to specific FcγRs and depends on sIC size. The assay identifies sICs in sera from SLE patients and autoimmune-prone mice as a novel biomarker of autoimmune disease.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Added Details in the M&M section. Minor revisions to the text. Updated and added references. Minor adjustments and corrections to the figures.
