Fig. 2: Immune-targeting autoantibodies in patients with COVID-19 have functional effects.
From: Diverse functional autoantibodies in patients with COVID-19
a, GM-CSF signalling assay performed with IgG from a patient with COVID-19 who was positive for anti-GM-CSF autoantibody (pink circles) and two uninfected healthcare workers (grey squares). Results are averages of technical duplicates from one experiment. b, CXCL1 (left) and CXCL7 (right) signalling assays performed with IgG from patients with COVID-19 who were positive for anti-CXCL1 or anti-CXCL7 autoantibody (AAb) and from healthcare workers (HCWs). Results are averages of three technical replicates or duplicates. RLU, relative luminescence unit. c, Macrophage phagocytosis assay performed with Raji (left) or Jurkat (right) cells, using plasma or IgG from patients with COVID-19 who were positive for anti-CD38 or anti-CD3ε autoantibody, respectively, anti-CD38 or anti-CD3ε monoclonal antibodies (positive controls), and plasma or IgG from healthcare workers, respectively (n = 1 for all groups). Technical replicates are shown. Results in b, c are representative of two independent experiments. d, Longitudinal comparisons of SARS-CoV-2 viral load between patients with (positive) and without (negative) autoantibodies against type I IFNs. Linear regressions (solid lines) and 95% confidence bands (shaded areas) for each group are displayed. d, day. n values include longitudinal samples from the same patient. e–g, Average per cent B cells (e), relative proportions of classical, intermediate and nonclassical monocytes (f) and average per cent CD4+ T cells (g) among peripheral leukocytes in healthcare workers and patients with COVID-19 stratified by disease severity and positive REAP reactivity (autoantibody-positive) (REAP score ≥ 2) against B-cell-displayed proteins (CD38, FcμR and FCRL3) (e), proteins preferentially displayed on classical and intermediate monocytes (CCR2, CCRL2, FFAR4, SYND4 and CPAMD8) (f) and CD3ε (g), respectively. Gating strategies for e–g are shown in Extended Data Fig. 8. Data from e, g are presented as box plots with the first quartile, median, third quartile, whiskers (minimum and maximum values within the first or third quartiles ± 1.5× the interquartile range), and individual data points indicated. Significance was determined using a generalized linear mixed model (d) (Methods) or a two-sided Wilcoxon rank-sum test (e). In b, c, e–g, n values indicate samples from unique patients. All error bars represent s.d.
