Influence of the season on vitamin D levels and regulatory T cells in patients with polymorphic light eruption

N A Schweintzger, A Gruber-Wackernagel, N Shirsath, F Quehenberger, B Obermayer-Pietsch, P Wolf, N A Schweintzger, A Gruber-Wackernagel, N Shirsath, F Quehenberger, B Obermayer-Pietsch, P Wolf

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).

Figures

Fig. 1. Tregs of the CD4+ subpopulation…
Fig. 1. Tregs of the CD4+ subpopulation and absolute Tregs are higher in the summer period but show no significant increase in Treg function (e.g. less T effector cell proliferation). PBMCs of PLE patients were stained with antibodies for CD4, CD127, CD25 and FoxP3. Individual percentages of Tregs as a proportion of (A) CD4+ cells and (B) all lymphocytes are shown. (C) Individual absolute Treg numbers from PLE patients were determined by flow cytometry and calculated using lymphocyte counts by automated blood cell analysis. (D) Individual Treg suppression assays where data are shown as individual 1 : 1 ratios, normalised to T effector cell proliferation alone (0 : 1 ratio = 100%). 1 : 1 ratio represents the results of co-culture of equal numbers of T effector (CD4+CD25–CD127+) and Tregs (CD4+CD25+CD127–). All data are plotted against day of year. (A–C) n = 26 PLE patients; (D) n = 12 PLE patients. P-Values for comparison of the two periods (January 10 to February 11 vs. April 17 to June 24) were determined by using the Mann–Whitney test.
Fig. 2. 25(OH)D serum levels were significantly…
Fig. 2. 25(OH)D serum levels were significantly higher in late spring/early summer (April 17 to June 24) compared to the winter period (January 10 to February 11), but did not correlate with absolute Treg numbers and function in PLE patients. (A) Individual 25(OH)D serum levels were determined and are plotted versus day of year. (B) Absolute numbers of Tregs and (C) data from Treg suppression assays are plotted against their respective 25(OH)D serum levels. Data from (C) shown are individual 1 : 1 ratios, normalised to T effector cell proliferation alone (0 : 1 ratio = 100%). 1 : 1 ratio represents the results of co-culture of equal numbers of T effector (CD4+CD25–CD127+) and Tregs (CD4+CD25+CD127–). (A) and (B) n = 26 PLE patients; (C) n = 12 PLE patients. P-Values were determined using (A) Mann–Whitney test and (B) and (C) Spearman correlation.
Fig. 3. Treg levels and function are…
Fig. 3. Treg levels and function are similar in PLE patients with 25(OH)D serum levels above or below 30 ng ml–1. (A) Absolute numbers of Tregs and (B) data of Treg suppression assays from patients with 25(OH)D serum levels below and at or above 30 ng ml–1 are shown. Data from (B) shown are individual 1 : 1 ratios, normalised to T effector cell proliferation alone (0 : 1 ratio = 100%). 1 : 1 ratio represents the results of co-culture of equal numbers of T effector (CD4+CD25–CD127+) and Tregs (CD4+CD25+CD127–). (A) n = 16 PLE patients with 25(OH)D serum levels at or above 30 ng ml–1 and 10 PLE patients with 25(OH)D serum levels below 30 ng ml–1; (B) n = 7 PLE patients with 25(OH)D serum levels at or above 30 ng ml–1 and 5 PLE patients with 25(OH)D serum levels below 30 ng ml–1. P-Values were determined by the Mann–Whitney test.

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