Narrowband UVB Phototherapy for Clinically Isolated Syndrome: A Trial to Deliver the Benefits of Vitamin D and Other UVB-Induced Molecules

Abstract

Low vitamin D and insufficient sun exposure are additive independent risk factors for the development of multiple sclerosis (MS). The usual measure of vitamin D status, serum 25-hydroxy vitamin D [25(OH)D], is also a marker of recent exposure to the UVB rays of sunshine. The main evidence for a protective effect for MS development of higher 25(OH)D comes from observational studies, but this study design cannot separate out whether 25(OH)D is acting as a marker of vitamin D status, sun exposure, or both. In light of a lack of definitive outcomes in MS patients after trials of vitamin D supplementation and the ability of narrowband UVB to induce vitamin D, as well as other immune-regulatory molecules in skin, the Phototherapy for Clinically Isolated Syndrome (PhoCIS) trial was established to investigate the benefits of narrowband UVB, in addition to supplemented vitamin D, on MS development in individuals with Clinically Isolated Syndrome. We propose that the PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with MS development and progression.

Tryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis

“…CIS patients (all participants in the PhoCIS trial)16, 17 donated blood again 3 months after their first venepuncture. There were no differences in the expression of IDO1, IDO2 and ARG2 mRNA in cells from the participants (Figure 3a, b and d).…”

“…The CIS patients (with clinical symptoms as detailed previously)17 donated blood within 120 days of confirmation of their first demyelinating event by MRI and were at high risk for MS conversion as their MRI satisfied Paty A or Paty B criteria 16, 17, 29. All CIS patients were participants in the PhoCIS trial,16, 17 with their baseline sample included in the present study. Seven of the eight patients with MS had recent clinical symptoms but their MRI showed a diagnosis of MS by 2010 McDonald criteria; that is, their cerebral and/or spinal cord MRI indicated that they had multiple demyelinating lesions separated in time and space 30.…”

“…The CIS patients were randomly assigned into two groups as previously described. 16,17 One group received narrowband UVB phototherapy (wavelengths 311-312 nm) 3 times per week for 8 weeks (24 exposures in total) to their full body. 16,17 Blood samples were again collected at 3 months and PBMCs isolated.…”

“…16,17 One group received narrowband UVB phototherapy (wavelengths 311-312 nm) 3 times per week for 8 weeks (24 exposures in total) to their full body. 16,17 Blood samples were again collected at 3 months and PBMCs isolated. Baseline and 3-month paired blood samples were available for enzyme and cytokine mRNA analysis from 15 CIS participants (8 receiving phototherapy and 7 in the no phototherapy (i.e.…”

“…The aim was to determine whether changes in catabolic enzyme expression were a characteristic of the early form of disease, or reflected a later development in established MS. The effect of a potential immunomodulatory treatment, namely narrowband UVB phototherapy (311–312 nm),16, 17 on the expression of IDO and ARG by PBMCs was also examined. Associations between IDO and ARG expression and the function of the PBMCs were assessed by analysis of mRNA levels of genes encoding pro‐ and anti‐inflammatory cytokines.…”