Contributions
Abstract: P623
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Vitamin D upregulates IL-2 receptor alpha chain (CD25) expression on CD4+ T cells in vitro. Both activated T cells and regulatory T cells (Treg) express CD25. Furthermore, CD25-targeted therapies are efficacious in relapsing remitting MS (RRMS). To differentiate between enhanced CD25 expression on activated T cells and Treg, we investigated the effect of high-dose vitamin D3 supplementation on CD25 protein expression on these T cell subsets directly ex-vivo.
Methods: We conducted a sub-study of a randomized controlled clinical trial (RCT; NCT01285401) among interferon-beta treated RRMS patients, randomized to 48-weeks vitamin D3 (N=30) or placebo (N=23). With flowcytometry, CD25 mean fluorescence intensity (MFI) was quantified on the total CD4+ T cell-fraction, and in the CD4+ Treg-fraction (CD25+FoxP3+, CD25+CD127-, CD25+CD127-FoxP3+) at baseline and at 48 weeks.
Results: In both treatment arms, there was no difference in total CD4+ T cell CD25 MFI during follow-up. In the placebo arm, there was a significant loss of CD25-MFI on all Treg definitions in 48 weeks of treatment (for CD25+CD127-FoxP3+ Treg MFI 5544 to 4871, P=0.002), which was not seen in the vitamin D3 group (MFI 5547 to 5124, P=0.100).
Conclusions: A loss of CD25 protein expression on Treg may be an early detrimental event in RRMS, which is prevented by supplementation of vitamin D3. Promotion of CD25-expression appears to be restricted to beneficial Treg, and not potentially encephalitogenic activated T cells. Clinical outcomes of RCT"s on vitamin D3 supplementation should confirm the relevance of this mechanism for MS.
Disclosure:
LR reports no conflicts of interest;
AHM reports no conflicts of interest,
RH received honoraria for advisory boards and research grants from BIOGEN,SANOFI AVENTIS, NOVARTIS and MERCK,
JD reports no conflicts of interest,
JS reports no conflicts of interest.
Abstract: P623
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Vitamin D upregulates IL-2 receptor alpha chain (CD25) expression on CD4+ T cells in vitro. Both activated T cells and regulatory T cells (Treg) express CD25. Furthermore, CD25-targeted therapies are efficacious in relapsing remitting MS (RRMS). To differentiate between enhanced CD25 expression on activated T cells and Treg, we investigated the effect of high-dose vitamin D3 supplementation on CD25 protein expression on these T cell subsets directly ex-vivo.
Methods: We conducted a sub-study of a randomized controlled clinical trial (RCT; NCT01285401) among interferon-beta treated RRMS patients, randomized to 48-weeks vitamin D3 (N=30) or placebo (N=23). With flowcytometry, CD25 mean fluorescence intensity (MFI) was quantified on the total CD4+ T cell-fraction, and in the CD4+ Treg-fraction (CD25+FoxP3+, CD25+CD127-, CD25+CD127-FoxP3+) at baseline and at 48 weeks.
Results: In both treatment arms, there was no difference in total CD4+ T cell CD25 MFI during follow-up. In the placebo arm, there was a significant loss of CD25-MFI on all Treg definitions in 48 weeks of treatment (for CD25+CD127-FoxP3+ Treg MFI 5544 to 4871, P=0.002), which was not seen in the vitamin D3 group (MFI 5547 to 5124, P=0.100).
Conclusions: A loss of CD25 protein expression on Treg may be an early detrimental event in RRMS, which is prevented by supplementation of vitamin D3. Promotion of CD25-expression appears to be restricted to beneficial Treg, and not potentially encephalitogenic activated T cells. Clinical outcomes of RCT"s on vitamin D3 supplementation should confirm the relevance of this mechanism for MS.
Disclosure:
LR reports no conflicts of interest;
AHM reports no conflicts of interest,
RH received honoraria for advisory boards and research grants from BIOGEN,SANOFI AVENTIS, NOVARTIS and MERCK,
JD reports no conflicts of interest,
JS reports no conflicts of interest.