The Aryl Hydrocarbon Receptor–Dependent TGF-α/VEGF-B Ratio Correlates With Disease Subtype and Prognosis in Multiple Sclerosis. Issue 5 (September 2021)

• Record Type: Journal Article
• Authors: Cirac, Ana; Tsaktanis, Thanos; Beyer, Tobias; Linnerbauer, Mathias; Andlauer, Till; Grummel, Verena; Nirschl, Lucy; Loesslein, Lena; Quintana, Francisco J.; Hemmer, Bernhard; Rothhammer, Veit
• Is Part Of: Neurology. Volume 8:Issue 5(2021)
• Publication Date: 2021-09
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000001043
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : Objective: To evaluate the aryl hydrocarbon receptor (AHR)-dependent transforming growth factor alpha (TGF-α)/vascular endothelial growth factor B (VEGF-B) ratio, which regulates the effects of metabolic, dietary, and microbial factors on acute and chronic CNS inflammation, as a potential marker in multiple sclerosis (MS). Methods: TGF-α, VEGF-B, and AHR agonistic activity were determined in serum of 252 patients with relapsing-remitting (RR) MS, primary and secondary progressive MS, as well as during active disease (clinically isolated syndrome [CIS] and RRMS relapse). Results: The TGF-α/VEGF-B ratio and AHR agonistic activity were decreased in all MS subgroups with a stable disease course as compared to controls. During active CNS inflammation in CIS and RRMS relapse, the TGF-α/VEGF-B ratio and AHR agonistic activity were increased. Conversely, in patients with minimal clinical impairment despite long-standing disease, the TGF-α/VEGF-B ratio and AHR agonistic activity were unaltered. Finally, the TGF-α/VEGF-B ratio and AHR agonistic activity correlated with neurologic impairment and time to conversion from CIS to MS. Conclusions: The AHR-dependent TGF-α/VEGF-B ratio is altered in a subtype, severity, and disease activity–specific manner and correlates with time to conversion from CIS to MS. It may thus represent a novel marker and serve as additive guideline for immunomodulatory strategies in MS. Classification of Evidence: This study provides Class III evidence that serum levels of AHR, TGF-α, and VEGF-B distinguish subtypes of MS and predict the severity and disease activity of MS.