Ostkamp, Patrick, Salmen, Anke ORCID: 0000-0002-4751-299X, Pignolet, Beatrice, Goerlich, Dennis, Andlauer, Till F. M., Schulte-Mecklenbeck, Andreas ORCID: 0000-0003-3855-4706, Gonzalez-Escamilla, Gabriel, Bucciarelli, Florence, Gennero, Isabelle ORCID: 0000-0002-8572-7852, Breuer, Johanna, Antony, Gisela, Schneider-Hohendorf, Tilman ORCID: 0000-0002-3717-5176, Mykicki, Nadine, Bayas, Antonios, Bergh, Florian Then, Bittner, Stefan, Hartung, Hans-Peter, Friese, Manuel A., Linker, Ralf A., Luessi, Felix, Lehmann-Horn, Klaus, Muehlau, Mark, Paul, Friedemann, Stangel, Martin, Tackenberg, Bjorn, Tumani, Hayrettin, Warnke, Clemens, Weber, Frank, Wildemann, Brigitte, Zettl, Uwe K., Ziemann, Ulf, Muller-Myhsok, Bertram, Kuempfel, Tania, Klotz, Luisa, Meuth, Sven G., Zipp, Frauke ORCID: 0000-0002-1231-1928, Hemmer, Bernhard ORCID: 0000-0001-5985-6784, Hohlfeld, Reinhard, Brassat, David, Gold, Ralf, Gross, Catharina C., Lukas, Carsten ORCID: 0000-0002-8562-9697, Groppa, Sergiu, Loser, Karin, Wiendl, Heinz and Schwab, Nicholas (2021). Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. Proc. Natl. Acad. Sci. U. S. A., 118 (1). WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Multiple sclerosis (MS) disease risk is associated with reduced sunexposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies (n(NationMS) = 946, n(BIONAT) = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-beta-treated patients. In carriers of MC1R:rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests benefidal effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ostkamp, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salmen, AnkeUNSPECIFIEDorcid.org/0000-0002-4751-299XUNSPECIFIED
Pignolet, BeatriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goerlich, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andlauer, Till F. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte-Mecklenbeck, AndreasUNSPECIFIEDorcid.org/0000-0003-3855-4706UNSPECIFIED
Gonzalez-Escamilla, GabrielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bucciarelli, FlorenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gennero, IsabelleUNSPECIFIEDorcid.org/0000-0002-8572-7852UNSPECIFIED
Breuer, JohannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antony, GiselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider-Hohendorf, TilmanUNSPECIFIEDorcid.org/0000-0002-3717-5176UNSPECIFIED
Mykicki, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bayas, AntoniosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergh, Florian ThenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bittner, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartung, Hans-PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friese, Manuel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linker, Ralf A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luessi, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann-Horn, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muehlau, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paul, FriedemannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stangel, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tackenberg, BjornUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tumani, HayrettinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warnke, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wildemann, BrigitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zettl, Uwe K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziemann, UlfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller-Myhsok, BertramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuempfel, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klotz, LuisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meuth, Sven G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zipp, FraukeUNSPECIFIEDorcid.org/0000-0002-1231-1928UNSPECIFIED
Hemmer, BernhardUNSPECIFIEDorcid.org/0000-0001-5985-6784UNSPECIFIED
Hohlfeld, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brassat, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gold, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gross, Catharina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lukas, CarstenUNSPECIFIEDorcid.org/0000-0002-8562-9697UNSPECIFIED
Groppa, SergiuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loser, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiendl, HeinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwab, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-607222
DOI: 10.1073/pnas.2018457118
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 118
Number: 1
Date: 2021
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
VITAMIN-D; INTERFERON-BETA; I INTERFERON; 25-HYDROXYVITAMIN D; DISEASE-ACTIVITY; UV-RADIATION; SUN EXPOSURE; RECEPTOR; RISK; HORMONEMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60722

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