Publication brief: Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

Sun exposure is associated with decreased multiple sclerosis (MS) severity, but may be detrimental for photosensitive patients, according to two multicentre studies by Ostkamp et al. (2020), published in PNAS, National Academy of Sciences of the USA.

The melanocortin 1 receptor (MC1R) gene provides instructions for making the melanocortin 1 receptor protein, important for pigmentation, and a predictor of hair colour. People who carry an MC1R gene loss-of function variant, known as MC1R:rs1805008(T), are more likely to have red hair and fair skin. Individuals with this allele have a 91.5% increased chance of experiencing a severe reaction to sunlight, according to the study.

Blood Vitamin D concentration (VitD) has been used as a proxy for ultraviolet radiation (UVR) exposure in several studies investigating the effect of sun exposure in MS severity and progression. However, there is uncertainty whether other UVR-dependent pathways, unrelated to VitD, also modulate MS severity. In support of the latter, the authors highlight a paper by Langer-Gould et al. (2018) suggesting that increased lifetime UVR exposure was associated with a lower risk of MS, independent of VitD levels in fair and dark skin populations. However, higher VitD levels were only associated with a lower risk of MS in the fair skinned group.

In light of the inconclusive evidence, Ostkamp et al. set out to measure the effects of VitD and latitude, in addition to assessing effect-modification by photosensitivity-associated MC1R variants.

Correlations were found between VitD/latitude, VitD/disease severity, and latitude/disease severity. High VitD was associated with a reduced MS severity, reduced risk for relapses, and slower disease progression, in both cohorts (nNationMS = 946, nBIONAT = 990). The authors acknowledged that this did not prove that VitD is the causal factor. Photosensitive participants carrying the particular MC1R gene variant, showed lower latitude was associated with higher magnetic resonance imaging (MRI) disease activity, whereas noncarriers showed reduced MRI disease activity at lower latitudes. MRI is an important tool for monitoring disability progression in MS, highlighting brain lesions caused by the disease. This may suggest that sun exposure may increase the risk of relapse and long-term disability for photosensitive MS patients.

As with all studies with uncontrolled variables it is important to recognise the limitations and interpret them with care. The effect of the MC1R variant was found to be only nominally significant, meaning repeats in larger cohorts are needed to confirm their findings. Further, the study did not consider participants’ recent exposure to UVR outside of the study, for instance from travel and photoprotective habits.

This study highlights the complexity of UVR-dependent pathways and the effects exerted on the body in both health and in disease states. Moreover, it shows the importance of better understanding the interaction between light and the human body.

CLINUVEL’s heritage as experts in the interaction between light and health provides the foundation for the Company’s growth and development. CLINUVEL’s pipeline is focussed on developing treatments for patients with genetic, metabolic, and life-threatening disorders, as well as healthcare solutions for the general population.

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