Journal: Cell Reports Medicine
Article Title: Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets
doi: 10.1016/j.xcrm.2022.100894
Figure Lengend Snippet: Neutralizing anti-IFN-Abs in patients with SLE inversely correlate with circulating IFNα (A) Heatmap showing levels (arbitrary units [a.u.]) of anti-cytokine autoantibodies (IFNα pool, IFNω, IFNλ pool, IFNβ1, Th17 pool, IFNγ, IL-pool, and TNF) in 474 patients with SLE and 312 controls measured by luciferase immunoprecipitation system (LIPS) assay. (B and C) Levels of (B) anti-IFNα (positive cutoff 1.7 a.u.) and (C) anti-IFNω autoantibodies (positive cut-off 2.3 a.u.) in sera from 474 patients with SLE and 312 controls. (D) Correlation between serum titers of anti-IFNα and anti-IFNω-autoantibodies in autoantibody-positive patients. (E) IgG subclasses of anti-IFN-Abs represented as luciferase units (LUs) for patients with SLE (n = 59) and controls (n = 6). (F) Serum IFNα concentration of patients with SLE with high (>100 a.u.), low (<100 a.u.), or negative (<1.9 a.u.) titers of anti-IFN-Abs and controls. (G) Correlation between IC50 and titer of neutralizing anti-IFN-Abs. (H) Correlation between serum IFNα concentrations (measured by Simoa assay) and anti-IFNα-autoAb titers for patients with SLE grouped according to neutralization capacity (neutralizing IC50 > 100, non-neutralizing IC50 < 100). (I) Interferon score of PBMCs isolated ex vivo from patients with neutralizing (n = 8) or non-neutralizing (n = 16) anti-IFN-Abs, anti-IFN-Ab-negative patients with SLE (n = 54), and controls (n = 17). Data represented are a cumulative score of the expression of ISGs MX1 , MCL1 , IRF9 , and STAT1 measured by qRT-PCR and relative to GAPDH . (J) Representative graph showing the titers of neutralizing anti-IFN-Abs against IFNα subtypes longitudinally in one patient with SLE. ∗p < 0.05, ∗∗p = 0.01, ∗∗∗∗p < 0.0001 by (D) unpaired Student’s t test with Welch’s correction, (E and F) Kruskal-Wallis test with Dunn’s multiple comparison, (G) two-tailed Spearman correlation, and (I) Mann-Whitney test. Error bars are shown as mean ± SEM.
Article Snippet: Multi-IFN-Alpha subtype quantification Digital ELISA kit (Simoa) , Quanterix , Beta-version.
Techniques: Luciferase, Immunoprecipitation, Lips Assay, Concentration Assay, Neutralization, Isolation, Ex Vivo, Expressing, Quantitative RT-PCR, Comparison, Two Tailed Test, MANN-WHITNEY
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![Neutralizing anti-IFN-Abs in patients with SLE inversely correlate with circulating IFNα (A) Heatmap showing levels (arbitrary units [a.u.]) of anti-cytokine autoantibodies (IFNα pool, IFNω, IFNλ pool, IFNβ1, Th17 pool, IFNγ, IL-pool, and TNF) in 474 patients with SLE and 312 controls measured by luciferase immunoprecipitation system (LIPS) assay. (B and C) Levels of (B) anti-IFNα (positive cutoff 1.7 a.u.) and (C) anti-IFNω autoantibodies (positive cut-off 2.3 a.u.) in sera from 474 patients with SLE and 312 controls. (D) Correlation between serum titers of anti-IFNα and anti-IFNω-autoantibodies in autoantibody-positive patients. (E) IgG subclasses of anti-IFN-Abs represented as luciferase units (LUs) for patients with SLE (n = 59) and controls (n = 6). (F) Serum IFNα concentration of patients with SLE with high (>100 a.u.), low (<100 a.u.), or negative (<1.9 a.u.) titers of anti-IFN-Abs and controls. (G) Correlation between IC50 and titer of neutralizing anti-IFN-Abs. (H) Correlation between serum IFNα concentrations (measured by <t>Simoa</t> assay) and anti-IFNα-autoAb titers for patients with SLE grouped according to neutralization capacity (neutralizing IC50 > 100, non-neutralizing IC50 < 100). (I) Interferon score of PBMCs isolated ex vivo from patients with neutralizing (n = 8) or non-neutralizing (n = 16) anti-IFN-Abs, anti-IFN-Ab-negative patients with SLE (n = 54), and controls (n = 17). Data represented are a cumulative score of the expression of ISGs MX1 , MCL1 , IRF9 , and STAT1 measured by qRT-PCR and relative to GAPDH . (J) Representative graph showing the titers of neutralizing anti-IFN-Abs against IFNα subtypes longitudinally in one patient with SLE. ∗p < 0.05, ∗∗p = 0.01, ∗∗∗∗p < 0.0001 by (D) unpaired Student’s t test with Welch’s correction, (E and F) Kruskal-Wallis test with Dunn’s multiple comparison, (G) two-tailed Spearman correlation, and (I) Mann-Whitney test. Error bars are shown as mean ± SEM.](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_3953/pmc09873953/pmc09873953__gr1.jpg)
