It has long been acknowledged that multiple sclerosis disease risk is associated with reduced sun-exposure, and subsequent low vitamin D levels. The study by Ostkamp et al. now assessed the relationship between measures of sun exposure and MS severity. For this, the researchers analyzed data of around 2,000 patients from the German NationMS- and the French BIONAT cohort. To approximate a patients’ sunlight exposure, the researchers used serum vitamin D measurements, the geographical latitude of residence, and UV-light estimates extracted from the recordings of NASA satellites. As expected, high serum vitamin D could be shown to be associated with a reduced MS severity score, reduced risk for relapses, and lower disability accumulation over time. Furthermore, low latitude associated with higher vitamin D levels, a lower MS severity score, fewer gadolinium-enhancing lesions, and lower disability accumulation over time. As an exception, no association between latitude and disability was found in patients who were treated with IFN-β before the start of the study. This lined up with a finding from an RNA-sequencing analysis, in which the researchers could show an induction of the type I interferon-pathway in a small cohort of patients, who were treated with narrowband UVB-light for six weeks.

Patrick Ostkamp was in the team of scientists who analysed the cohort data. (Photo: Leßmann)

Therefore, as UVB potentially initiates an interferon response itself, it might be possible that no effect of UVB can be observed in patients whose blood is already saturated with interferons. Although the study shows that sunlight exposure has a beneficial effect on MS severity, the researchers argue against excessive sun exposure, as the observed effects of UV-light were of comparably low magnitude, and photosensitive patients who carried a genetic variant of the melanocortin-1-receptor (an important factor for pigmentation) even seemed to worsen upon increased sunlight exposure, according their MRI activity.

Reference: Ostkamp P, Salmen A, Pignolet B, Görlich D, Andlauer TFM, Schulte-Mecklenbeck A, Gonzalez-Escamilla G, Bucciarelli F, Gennero I, Breuer J, Antony G, Schneider-Hohendorf T, Mykicki N, Bayas A, Then Bergh F, Bittner S, Hartung H-P, Friese MA, Linker RA, Luessi F, Lehmann-Horn K, Mühlau M, Paul F, Stangel M, Tackenberg B, Tumani H, Warnke C, Weber F, Wildemann B, Zettl UK, Ziemann U, Müller-Myhsok B, Kümpfel T, Klotz L, Meuth SG, Zipp F, Hemmer B, Hohlfeld R, Brassat D, Gold R, Gross CC, Lukas C, Groppa S, Loser K, Wiendl H, Schwab N, German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network. 2021. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. Proc Natl Acad Sci U S A. 118(1):e2018457118.

Each year, the German Society for Immunology (DGfI) recognizes young scientists who have made an outstanding contribution in the field of immunology. This year, Dr. Beatrice Wasser, a Postdoc in the group of Prof. Frauke Zipp and Prof. Stefan Bittner in the Department of Neurology, was award the Herbert Fischer Prize for Neuroimmunology for her investigation of the mechanism by which cells of the central nervous system (CNS) can control autoreactive T lymphocytes. Dr. Wasser was able to show, for the first time, that myeloid cells in the CNS can trap and kill invading pathogenic T cells. This novel defense pathway could potentially be exploited, leading to a new therapy for T cell-induced autoimmune diseases such as multiple sclerosis.

This work was recently published in the Journal of Experimental Medicine:
Wasser B, Luchtman D, Löffel J, Robohm K, Birkner K, Stroh A, Vogelaar CF, Zipp F, Bittner S. CNS-localized myeloid cells capture living invading T cells during neuroinflammation. J Exp Med 2020; 217(6): e20190812.
The official press release of the DGfI is available here.

Happy about the new findings from the MS-TWIN study: PhD student Claudia Janoschka (right) and group leader Prof. Luise Klotz (Photo: Deiters-Keul)

The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like multiple sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, SFB researchers from Munich and Muenster made use of a unique cohort of 43 monozygotic twin pairs clinically discordant for MS and searched for disease-related peripheral immune signatures in a systems biology approach covering a broad range of adaptive and innate immune populations on the protein level. Results of their work were published in the latest issue of the prestigious journal PNAS.
Despite disease discordance, the immune signatures of MS-affected and unaffected cotwins were remarkably similar. Twinship alone contributed 56% of the immune variation, whereas MS explained 1 to 2% of the immune variance. Notably, distinct traits in CD4+ effector T cell subsets emerged when Lisa Ann Gerdes, Claudia Janoschka and colleagues focused on a subgroup of twins with signs of subclinical, prodromal MS in the clinically healthy cotwin. Some of these early-disease immune traits were confirmed in a second independent cohort of untreated early relapsing-remitting MS patients. Early involvement of effector T cell subsets thus points to a key role of T cells in MS disease initiation.

Adapted from.
Gerdes LA° Janoschka C°, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A, Ertl-Wagner B, Barkhof F, Meuth SG, Kümpfel T, Wiendl H°, Hohlfeld R*, Klotz L*. Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proc Natl Acad Sci U S A 117(35):21546-21556. (°,*= equal contribution)