RT Journal Article SR Electronic T1 The Aryl Hydrocarbon Receptor–Dependent TGF-α/VEGF-B Ratio Correlates With Disease Subtype and Prognosis in Multiple Sclerosis JF Neurology - Neuroimmunology Neuroinflammation JO Neurol Neuroimmunol Neuroinflamm FD Lippincott Williams & Wilkins SP e1043 DO 10.1212/NXI.0000000000001043 VO 8 IS 5 A1 Cirac, Ana A1 Tsaktanis, Thanos A1 Beyer, Tobias A1 Linnerbauer, Mathias A1 Andlauer, Till A1 Grummel, Verena A1 Nirschl, Lucy A1 Loesslein, Lena A1 Quintana, Francisco J. A1 Hemmer, Bernhard A1 Rothhammer, Veit YR 2021 UL http://nn.neurology.org/content/8/5/e1043.abstract AB 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.AHR=aryl hydrocarbon receptor; CIS=clinically isolated syndrome; EDSS=Expanded Disability Status Scale; MS=multiple sclerosis; PPMS=primary progressive MS; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS; TGF-α=transforming growth factor alpha; VEGF-B=vascular endothelial growth factor B