Abstract
The exact mechanisms of photohardening in polymorphic light eruption (PLE) are still unknown, but medical photohardening was shown to increase regulatory T cell (Treg) numbers in the blood of PLE patients, similar to natural hardening. Furthermore, oral vitamin D supplementation increased peripheral Tregs in healthy individuals. We herein report on a post hoc analysis of 26 screened PLE patients of a clinical trial (ClinicalTrials.gov No. NCT01595893), in which the influence of the progressing season was investigated on baseline CD4+CD25+FoxP3+CD127- Treg numbers by flow cytometry and Treg suppressive function by co-culture assays with T effector cells as a secondary endpoint, together with 25-hydroxy vitamin D (25(OH)D) serum levels at the study's screening visit, taking place in the period from January to June. The mean 25(OH)D serum level of all patients was 33.2 ng ml(-1). Ten of those patients (38.5%) were identified with low 25(OH)D levels (<30 ng ml(-1)). Significantly higher baseline 25(OH)D serum levels (plus 34.4%; P = 0.0182) as well as higher relative Treg percentages in CD4+ population (plus 62.8%; P = 0.0157) and in total lymphocyte population (plus 59.6%; P = 0.0372) and higher absolute Treg numbers (plus 100.2%; P = 0.0042) were observed in the late spring/early summer period (April to June) compared to the winter period (January to February). No significant relationship was observed when Treg numbers and function were correlated with 25(OH)D levels. These data indicate that in PLE patients Treg numbers and their suppressive function are independent of vitamin D serum levels and suggest that UV light and/or other seasonal factors may affect these cells via the non-vitamin D related pathway(s).
Highlights
Itchy skin lesions of different morphologies are provoked by first intense sun exposure in spring or early summer and a so called “skin hardening effect” is usually observed during the summer season resulting in the development of tolerance even of higher sun dosages.[2,7,8]
Absolute and relative Treg numbers of Polymorphic light eruption (PLE) patients are higher towards summer The analysis of this report focuses on investigating a possible influence of season on baseline Treg numbers, Treg function and vitamin D serum levels in 26 PLE patients at the time point of first study visit (TP1), taking place in the period spanning from January to June, whereas the other time points were omitted from the present analysis
In this study we analysed the potential effect of the season and found that PLE patients tested towards summer displayed higher relative and absolute Treg numbers as well as 25(OH)D serum levels compared to patients tested in the winter period
Summary
Medical phototherapy modalities such as broadband UVB, narrowband 311 nm UVB or psoralen plus UVA (PUVA) photochemotherapy.[5,8,9]. Said so, decreased Treg infiltration was observed in UVA1-provoked skin lesions of PLE patients.[25] PLE patients showed an increase in Treg numbers together with a trend for improvement of the suppressive function after medical photohardening therapy.[26] Serum levels of vitamin D correlated positively with the suppressive capacity of Tregs in multiple sclerosis patients, proposing vitamin D as an important mediator of T cell regulation via inhibition of Th1 and Th17 cells.[27,28,29] Gruber-Wackernagel et al.[30] showed that pretreatment of the PLE-prone skin with a 1,25dihydroxyvitamin D3 analogue (calcipotriol)-containing cream reduced the symptoms of the disease upon subsequent experimental photoprovocation in all patients tested in contrast to a vehicle-cream. Higher Treg numbers were found to be independent of vitamin D
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