Fig 1: TGF-a/VEGF-B Ratio and AHR Agonistic Activity Are Decreased in Patients With MSTGF-a (A, B) and VEGF-B (C, D) levels as well as AHR agonistic activity (G, H) in serum samples of patients with RRMS in remission (n = 98), SPMS (n = 44), PPMS (n = 36), and their respective controls (A, C, E, G: n = 43; B, D, F, H: n = 16) were assessed. TGF-a and VEGF-B levels were measured in pg/mL using a human TGF-a or VEGF-B ELISA. TGF-a/VEGF-B ratio (E, F) was determined by dividing TGF-a levels by VEGF-B levels. An AHR ligand–sensitive luciferase assay was used. Relative activity was calculated by dividing firefly luciferase activity (pGud-Luc) by Renilla luciferase activity (pTK-Renilla). Values are means of duplicate measurements. Lines represent median and interquartile range. Significance levels were derived using nonparametric tests (Mann-Whitney test and Kruskal-Wallis test with the Dunn multiple comparison test correcting for multiple comparisons). ****p < 0.0001, ***p < 0.001, **p < 0.001, *p < 0.01, and ns = nonsignificant. AHR = aryl hydrocarbon receptor; MS = multiple sclerosis; PPMS = primary progressive MS; RRMS = relapsing-remitting MS; SPMS = secondary progressive MS; TGF-a = transforming growth factor alpha; VEGF-B = vascular endothelial growth factor B.
Fig 2: TGF-a/VEGF-B Ratio and AHR Agonistic Activity Correlate With the EDSS in RRMSTGF-a/VEGF-B ratio (A) and AHR agonistic activity (B) in serum samples of patients with RRMS in remission (n = 98) were assessed. TGF-a and VEGF-B levels were measured in pg/mL using a human TGF-a or VEGF-B ELISA. TGF-a/VEGF-B ratio was determined by dividing TGF-a levels by VEGF-B levels. An AHR ligand–sensitive luciferase assay was used. Relative activity was calculated by dividing firefly luciferase activity (pGud-Luc) by Renilla luciferase activity (pTK-Renilla). Values are presented as means of duplicate measurements. Line shows linear regression of the TGF-a/VEGF-B ratio or AHR agonistic activity and patients' EDSS. Significance levels were derived using Spearman correlation analysis (A: Spearman r = -0.2427; R2 = 0.059; B: Spearman r = -0.2433; R2 = 0.059). AHR = aryl hydrocarbon receptor; EDSS = Expanded Disability Status Scale; RRMS = relapsing-remitting multiple sclerosis; TGF-a = transforming growth factor alpha; VEGF-B = vascular endothelial growth factor B.
Fig 3: TGF-a/VEGF-B Ratio and AHR Agonistic Activity Are Upregulated in RRMS During Relapse Compared With RRMS in RemissionTGF-a (A) and VEGF-B (B) levels as well as AHR agonistic activity (D) were assessed in serum samples of patients with RRMS in remission (n = 98), RRMS during relapse (n = 54), and controls (n = 44). TGF-a and VEGF-B levels were measured in pg/mL using a human TGF-a or VEGF-B ELISA. TGF-a/VEGF-B ratio (C) was determined by dividing TGF-a levels by VEGF-B levels. An AHR ligand–sensitive luciferase assay was used. Relative activity was calculated by dividing firefly luciferase activity (pGud-Luc) by Renilla luciferase activity (pTK-Renilla). Values are means of duplicate measurements. Lines represent median and interquartile range. Significance levels were derived using the nonparametric Kruskal-Wallis test with the Dunn multiple comparison test correcting for multiple comparisons. ****p < 0.0001, ***p < 0.001, **p < 0.001, *p < 0.01, and ns = nonsignificant. AHR = aryl hydrocarbon receptor; RRMS = relapsing-remitting multiple sclerosis; TGF-a = transforming growth factor alpha; VEGF-B = vascular endothelial growth factor B.
Fig 4: TGF-a/VEGF-B Ratio and AHR Agonistic Activity Are Upregulated in Clinically Isolated Syndrome Compared With RRMS in RemissionTGF-a (A) and VEGF-B (B) levels as well as AHR agonistic activity (D) were assessed in serum samples of patients with RRMS in remission (n = 98), CIS (n = 20), and controls (n = 44). TGF-a and VEGF-B levels were measured in pg/mL using a human TGF-a or VEGF-B ELISA. TGF-a/VEGF-B ratio (C) was determined by dividing TGF-a levels by VEGF-B levels. An AHR ligand–sensitive luciferase assay was used. Relative activity was calculated by dividing firefly luciferase activity (pGud-Luc) by Renilla luciferase activity (pTK-Renilla). Values are means of duplicate measurements. Lines represent median and interquartile range. Significance levels were derived using the nonparametric Kruskal-Wallis test with the Dunn multiple comparison test correcting for multiple comparisons. ****p < 0.0001, ***p < 0.001, **p < 0.001, *p < 0.01, and ns = nonsignificant. AHR = aryl hydrocarbon receptor; CIS = clinically isolated syndrome; RRMS = relapsing-remitting multiple sclerosis; TGF-a = transforming growth factor alpha; VEGF-B = vascular endothelial growth factor B.
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