Proteolytic cleavage of monocyte FcgRIIA inhibits clearance of ICs. (A) Monocytes were incubated with R848 or neutrophil supernatant before addition of RNP-ICs or beads. Phagocytosis was determined by flow cytometry. The experiment was repeated four (beads, RNase, RNP-IC+R848) or seven (PMN sup) times; combined results are shown and compared using paired Student’s t test (RNP-IC, P = 0.0003; Beads, P = 0.0007). (B) ICs were added to PBMCs with or without prior treatment with neutrophil supernatant (A). After phagocytosis for 30 min, remaining cell-free ICs were analyzed for C5a-inducing ability upon addition of 1% normal human serum. The experiment was repeated three times; combined results are shown and compared using paired t test (P = 0.0084). C) C5a serum levels were measured in healthy controls (HC, n = 9) and SLE patients (n = 36) by ELISA. Combined results are shown and analyzed using Mann-Whitney U test (P = 0.047). (D and E) Serum levels of C5a in SLE patients were related to ability of serum to induce shedding of FcgRIIA on healthy control neutrophils. In D, combined results from 35 SLE patients are shown and analyzed using Spearman’s correlation test (r = −0.42; P = 0.011). In E, combined results are shown from SLE patients inducing shedding (n = 15) or not (n = 20), and compared using Mann-Whitney U test (P = 0.0281). *, P < 0.05; **, P < 0.01; ***, P < 0.001.