Investigators observed that some patients had improvements in their multiple sclerosis (MS) severity with increased sun exposure, whereas photosensitive individuals and those taking certain medications did not see the same effects.
The study builds on evidence that has demonstrated sunlight exposure to be a risk factor for MS development. Investigators said that there has been some debate over whether ultraviolet radiation (UVR) and vitamin D quantities have an effect on MS severity as well. Additionally, reports are scarce on whether the latitude where a person lives can be a proxy of sun exposure for large populations or whether interferon-beta (IFN-β) administration modulates vitamin D production.
Therefore, this study used vitamin D levels and latitude as measures of sunlight exposure. It also examined the effect of these measures on patients who are carriers of MC1R:rs1805008(T), which is tied to increased sunlight sensitivity.
Investigators used the results from 2 multicenter cohort studies: the NationMS cohort from Germany and the BIONAT cohort from France. The NationMS cohort recruited from 2010-2017 and the BIONAT studied was published in 2014. Next-generation sequencing was used to assess whether medication and the MC1R gene can modify the effects of UVR and vitamin D.
“MC1R missense variants strongly increase an individual’s sensitivity to UVR and could, therefore, modify the beneficial effect of UVR on MS disease severity,” wrote the investigators.
The NationMS cohort included 946 treatment-naïve patients with clinically isolated syndrome or relapsing-remitting multiple sclerosis who were aged 18 or older and had a disease duration of less than 2 years. Genotyping for MCR1 was successful for 883 patients and longitudinal data was available for 798 patients. Overall, 650 (81.46%) patients received medication after baseline, 364 (45.61%) of whom received IFN-β.
The BIONAT cohort included 990 patients with MS, 808 (81.62%) of whom had available information on demographics, clinical subtype of MS, medication, and MS severity scores (MSSS). Nearly 60% of patients were receiving IFN-β at baseline and 5 patients received phototherapy.
Investigators found that living at a lower latitude was associated with higher levels of vitamin D in the NationMS cohort (β = -0.56; 95% CI, -1.030 to ‑0.090; P = .020) and the BIONAT cohort (β = -0.44; 95% CI, -0.87 to -0.018], P = .041), suggesting that latitude is a valid measure of sun exposure.
Worse MSSS were associated with lower vitamin D levels (β = -0.014; 95% CI, -0.026 to -0.002; P = .021) and higher latitude (β = 0.092; 95% CI, -0.016 to 0.168; P = .018) in patients in the NationMS cohort. A similar result was detected when investigators substituted latitude by satellite derived UVR estimates.
With patients receiving IFN-β in the BIONAT cohort, higher vitamin D levels corresponded to better disability scores (β = ‑0.022; 95% CI, -0.037 to -0.007; P = .007). However, contrary to the results from the NationMS cohort, latitude did not have clear trend on disability scores in IFN-β treated patients (β = -0.004; 95% CI, -0.076 to 0.068; P = .913).
“Since interactions between IFN-β treatment and vitD have been shown before and it is known that IFN-β modulates vitD synthesis, it is possible that the normal association between latitude and vitD is altered by IFN-β treatment,” wrote the investigators.
Moreover, a medication subgroup analysis showed that higher latitudes were associated with worse disability scores in patients who were last treated with a drug that was not IFN-β.
Higher vitamin D levels reduced risk of relapse by 1% for every 1 mg/mL of serum vitamin at baseline (HR 0.988; 95% CI, 0.978–0.999; P = .028). Baseline vitamin D levels were also linked with a lower grade of disability accumulation (β = −0.006; 95% CI, -0.012 to -0.0003; P = .046) and lower latitude was associated with a significantly lower change in disability status (β = 0.67; 95% CI 0.026–0.106; P = .001).
In patients with photosensitivity-associated MCR1 missense variants, the T allele of the high-penetrance variant, rs1805008, increased the odds of sunlight-induced severe reactions by 91.5% (OR 1.92; 95% CI, 1.040–3.560; P = .038), suggesting that sun exposure could be detrimental for patients who are photosensitive.
The only limitation that investigators noted was that information regarding location of vacations, individual clothing habits, and use of sunscreen were not available.
Ostkamp P, Salmen A, Pignolet B, et al. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. Proc Natl Acad Sci. Published online January 5, 2021. doi: 10.1073/pnas.2018457118