The Aryl Hydrocarbon Receptor-Dependent TGF-α/VEGF-B Ratio Correlates With Disease Subtype and Prognosis in Multiple Sclerosis

Cirac, Ana; Tsaktanis, Thanos; Beyer, Tobias; Linnerbauer, Mathias; Andlauer, Till; Grummel, Verena; Nirschl, Lucy; Loesslein, Lena; Quintana, Francisco J.; Hemmer, Bernhard und Rothhammer, Veit (2021): The Aryl Hydrocarbon Receptor-Dependent TGF-α/VEGF-B Ratio Correlates With Disease Subtype and Prognosis in Multiple Sclerosis. In: Neurology-Neuroimmunology & Neuroinflammation, Bd. 8, Nr. 5, e1043

Abstract

Objective To evaluate the aryl hydrocarbon receptor (AHR)-dependent transforming growth factor alpha (TGF-alpha)/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-alpha, 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-alpha/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-alpha/VEGF-B ratio and AHR agonistic activity were increased. Conversely, in patients with minimal clinical impairment despite long-standing disease, the TGF-alpha/VEGF-B ratio and AHR agonistic activity were unaltered. Finally, the TGF-alpha/VEGF-B ratio and AHR agonistic activity correlated with neurologic impairment and time to conversion from CIS to MS. Conclusions The AHR-dependent TGF-alpha/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-alpha, and VEGF-B distinguish subtypes of MS and predict the severity and disease activity of MS.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198