Fig. 7
In vivo functions of FHR1. a In AAV, FHR1 attaches to necrotic cells (arrow), surrounding fresh fibrinoid necrotic lesions in the glomerulus (asterisk) but not in healthy tissue (discontinued arrow) (n = 79). Glomeruli derived from ΔFHR1/3 AAV patients (n = 9) lack FHR1 signals. Bars = 20 µm. b FHR1 (red) signal is found on macrophages and damaged smooth muscle cells in atherosclerotic plaques in human heart valve (n = 4, bars = 50 µm) and arteries (n = 6, bars = 200 µm) of AS patients. FHR2 staining is located to the intima of arteries. MGTE = Masson Goldner Trichrome Elastica. c EMR2/FHR1 complexes in kidney biopsies of FHR1/3, but not of ΔFHR1/3 AAV patients as shown by PLA assay. DNA is stained with DAPI. Twelve pictures of 3 FHR1/3 and seven pictures of 2 ΔFHR1/3 were analyzed (unpaired two-tailed t-test). Bar = 10 µm. d Serum IL 1β and e CRP with FHR1/3 compared to ΔFHR1/3 AAV patients (d, e unpaired two-tailed t-test with Welch’s correction and Kruskal–Wallis Test). f FHR1 concentrations in healthy individuals and AAV patients (unpaired two-tailed t-test, Welch’s correction). g Estimated glomerular filtration rate (eGFR) decreases (Spearman correlation) and h percentage of relapses of AAV patients increases with growing FHR1 concentrations. i Addition of F(ab)2 fragments of a FHR1 antibody to NHS reduces monocytic IL-1β to a level comparable to inflammation in ΔFHR1/3 NHS triggered by necrotic cells. j Natural FHR1 monomers bound to FHR1 SCR1–2 and are replaced by FHR2, but k not by dimerization mutant FHR2DM. l FHR1 on necrotic cells in ΔFHR1/3 NHS increases IL-1 β, which is reduced by FHR2 but not m by FHR2DM. Data in a–b show box and whiskers from min to max with mean ± SEM. (Wilcoxon Signed Rank test) and data in i-m represent the mean ± SEM. of three to four independent experiments with different cell donors (unpaired two-tailed t-test). a–m *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001
