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Updated: Oct 27, 2025
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Published on: August 3, 2018
The Aryl Hydrocarbon Receptor-Dependent TGF-α/VEGF-B Ratio Correlates With Disease Subtype and Prognosis in Multiple
Ana Cirac1, Thanos Tsaktanis1, Tobias Beyer1
1From the Department of Neurology (A.C., T.T., T.B., M.L., T.A., V.G., L.N., B.H., V.R.), Klinikum Rechts der Isar, Technical University of Munich Department of Neurology (T.T., M.L., L.L., V.R.), University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg, Germany; Ann Romney Center for Neurologic Diseases (F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Germany.
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.
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