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