The major advancements of this reporter system include (i) a high accuracy and resolution regarding FcγR type‐specific activation compared to traditional indirect assessment via affinity measurements, (ii) a scalable and quantifiable assay providing flexible high‐throughput readouts in the nanomolar range, (iii) a reporter system sensitive to sIC size, (iv) a comprehensive panel including all human FcγRs, and (v) its putative suitability as a new clinical biomarker in SLE patients and, prospectively, further patients with autoimmune diseases. Here, FCGR2A is linked to systemic lupus erythematosus.