Sunlight-mediated Inter-organ Leukocyte Exchange
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis
Study type: Interventional

Summary: 
      Ultraviolet B (UVB) irradiation induces regulatory immune cell types that may transmigrate
      from the skin to the blood and to the central nervous system and exert regulatory effects.
      Vitamin D deficiency-associated gene variants should reduce this effect if this is mediated
      by vitamin D. For this study, participants will be irradiated with UVB for 4 weeks. Single
      cell RNA Sequencing will be performed on isolated immune cells from skin, blood and
      Cerebrospinal fluid (CSF), before and after irradiation.
    

Detailed description: 
      The aim of this study will be to increase the Vitamin D3-serum concentrations in Multiple
      Sclerosis patients via UVB radiation with regard to different Vitamin D deficit-associated
      genotypes and analyse the effects of Vitamin D increase and UVB radiation, in general, on
      their immune cells. Participants of this study will be recruited from the pool of already
      registered MS patients at the department of neurology at the UKM and from resident
      practitioners of the Neuroimmunologisches Kompetenznetzwerk Münsterland. The UVB radiation of
      the participants will take place during wintertime to avoid any interference by ambient
      sunlight. As the participants will not take any supplements of Vitamin D, their serum
      concentration should be very low. The participants will be screened beforehand for their
      Vitamin D deficit-associated single nucleotide polymorphism and sorted into two groups
      depending on their calculated risk scores. The patients will also receive a clinical
      assessment in the department of neurology and dermatology and a cranial MRT. 17 patients each
      will be sorted into one of two groups: either Vitamin D deficiency high-risk or low-risk. The
      UVB influence on Vitamin D-serum concentration increases between those two groups should then
      be dependent on the associated genotypes. We will track those changes by taking blood samples
      before and after the radiation. We will also take samples of the skin and, for participants
      opting in, cerebrospinal fluid (CSF). This will allow us to isolate single cells from each of
      the three compartments and sequence them on a RNA transcriptomic level following the 10x
      workflow. UVB radiation will induce immunomodulating effects in the skin and Vitamin D was
      shown to be one of those effects, as its synthesis is initiated by UVB radiation and its
      binding to Vitamin D receptors renders immune cells more regulatory. If differences in immune
      cell alterations were found between the two groups of risk scores, they should be attributed
      to the associated genotypes, shedding new light on the influence of Vitamin D on the
      pathogenesis of MS patients and on the immune system in general.

      By utilizing single-cell RNA-sequencing on isolated immune cells of those three compartments,
      before and after the UVB radiation, we will be able to have a relatively unbiased approach to
      investigating the influence of UVB radiation and, separately, Vitamin D on the immune cells.
      Specific cell signatures of sequenced immune cells from the three compartments will allow us
      to track the migration of the induced cells from the skin through the blood and into the CSF.
      Additionally, CSF and serum isolated from blood will be assessed for Epstein-Barr-Virus
      antibody titers and extracellular vesicles. All this data will contribute to our
      multidimensional analysis using bioinformatics workflows based on linear methods such as
      principal components analysis and non-linear tools based on neural networks and Bayesian
      variational inference.
    

Intervention name(s): 311 nm narrowband UVB irradiation
Intervention type(s): Device
Intervention description(s): Participants will be irradiated with 311nm UVB for 5 days per week and 4 weeks in total.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: UVB; scRNAseq