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. 2023 Jun 7;14:3280. doi: 10.1038/s41467-023-38383-y

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Overview of the VEBIOS ER discovery cohort. 756 HPA antibodies, targeting 408 candidate proteins, were used to analyse plasma samples using affinity proteomics. Log fold changes in antibody MFI (median fluorescent intensity) signal were calculated between VTE cases (n = 48) and controls (n = 48) in (b) citrate or (c) EDTA anticoagulated plasma; coloured circles indicate antibodies that generated signals significantly associated with VTE in both. MFI signals generated by these antibodies for controls (n = 48) and cases (n = 48) in (d) citrate plasma and (e) EDTA plasma. f Immunocapture-mass spectrometry identification of protein targets of HPA059937 (n = 3 of independent biological replicates). g Dual binder assays were developed using an anti-CFHR5 detection antibody, combined with HPA059937 (raised against SULF1), anti-CFHR5 HPA073894 or anti-CFHR5 HPA072446 as capture antibodies. Monoclonal anti-CFHR5 (MAB3845) was applied as detection antibody in the three combinations. CFHR5 levels in the citrated plasma samples were re-analysed, using the respective dual binder assays, to determine levels (MFI) in controls (n = 48) vs. cases (n = 48) and the correlation between the signal and those generated by the original single binder assay using HPA059937 [all p < 1E-04]. Dual binder assay using capture antibody HPA072446 with a recombinant protein standard and MAB3845 as detection antibody, was used for absolute quantification of CFHR5 in samples from: (h) VEBIOS ER and (i) VEBIOS Coagulation (controls = 135, cases = 142). CFHR5 concentration was measured in controls and cases, with associated OR (odds ratio per 1 standard deviation increase [h and i, left]) or used to determine the correlation with C-reactive protein (CRP), or D-dimer concentration [h and i, right panels]. All data in dot plots (1 d–i) are represented as median value with 95% CI (confidence interval). Case and control groups was compared using a linear model adjusting for age and sex in d, e, g, h and i.*****p < 0.00001, ****p < 0.0001, ***p < 0.001, **p < 0.01. Two-sided Spearman´s correlation analysis for h and i. For summary statistics see Supplementary data 1 [Tab_2, Panel A]. Source data are provided as a Source Data file (b–i).