Fig. 3: Identification of AIF-1 as a delimiting soluble marker for the IFN signature in non-responders. | Nature Communications

Fig. 3: Identification of AIF-1 as a delimiting soluble marker for the IFN signature in non-responders.

From: Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis

Fig. 3

a Correlation of ISGhi ncMo proportion with IFN\(\alpha \) score and delta ASDAS. P values were calculated using Pearson correlation (two-sided), shaded bands represent 95% confidence intervals. Left, the black line indicates the overall correlation slope, and the gray lines indicate the NR (steeper slope) and R groups. b Volcano plot comparing ISGhi ncMo and ncMo. Thresholds were set at absolute log2 fold change of 0.25 and adjusted P value of 0.05 (MAST (two-sided, BH adjustment)). c Experimental design to validate AIF-1 as a predictive biomarker of the response to treatment with TNF inhibitor (TNFi). Figure created with BioRender.com. Created in BioRender. https://BioRender.com/q70l192. d Gene expression of AIF1 by qRT-PCR compared between Rs (n = 10) and NRs (n = 8) using PBMCs from TNFi-treated SpA patients in the validation cohort 1 at baseline (Welch two-sample t-test (two-sided)). Data are presented as mean ± standard deviation. e Baseline serum level of AIF-1 measured by ELISA compared between Rs (n = 69) and NRs (n = 48), two-sided Mann-Whitney test. Three different criteria (BASDAI50, ASAS40, and ASAS20) were used to determine the clinical response at week 14. Data are presented as mean ± standard deviation. f, g ROC curve of baseline serum AIF-1 levels for predicting a non-response at week 14 (f), odds ratio analysis of serum AIF-1 levels for TNFi response prediction. The gray diamond represents the unadjusted odds ratio, while the red diamond represents the adjusted odds ratio, accounting for age, initial BASDAI, CRP, and ESR in the logistic regression model. After adjustment, the odds ratio remained significant at 6.96 (95% CI). Error bars indicate 95% confidence intervals, with center points representing odds ratios (unadjusted, gray; adjusted, red) (g). h Validation of baseline serum AIF-1 levels in an independent cohort (Validation cohort 3, n = 58). Data shown as mean ± standard error; statistical significance assessed by Wilcoxon rank sum test. Exact P-value = 3.64e-06. i Change in serum AIF-1 between week 0 (baseline) and week 14 after initiating TNFi (R n = 59, NR n = 39), two-sided t-test. Source data are provided as a Source Data file.

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