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PWE-023 Vitamin D Enhances The Ability of Anti-TNF Therapy to Suppress Dendritic Cell Activity in Crohn’s Disease
  1. PA Hendy1,2,
  2. D Reddi1,
  3. D Barnardo3,
  4. L Durant1,
  5. A Noble1,
  6. P Bhat1,
  7. N English1,
  8. SC Knight1,
  9. AL Hart1,2
  1. 1APRG, Imperial College
  2. 2Gastroenterology, St Mark’s Hospital, London, UK
  3. 3Research Unit (7th floor), Hospital Universitario de la Princesa, Madrid, Spain


Introduction Dendritic cells (DC) can determine whether the mucosal immune system mounts an inflammatory or regulatory response to antigen and may contribute to the pathogenesis of Crohn’s disease. Vitamin D down-regulates DC inflammatory responses and could prove beneficial as a treatment adjunct in Crohn’s. This study assessed the effect of high dose parenteral vitamin D treatment on circulating DC phenotype and function in patients with active luminal Crohn’s receiving anti-TNFα therapy.

Methods Peripheral blood mononuclear cells were isolated from 13 patients with active luminal Crohn’s and suboptimal vitamin D levels prior to and 6 weeks after starting anti-TNFα (infliximab) therapy. Patients with low vitamin D (<50nmol/L) were also given a single high dose of parenteral vitamin D (300,000 international units 1,25(OH)2 vitamin D3). Flow cytometry was used to identify total DC, (HLA-DR+ cells negative for markers of other cell lineages (CD3, CD14, CD16, CD19 & CD34)). DC were further subtyped as myeloid (mDC, CD11c+CD123). Expression of phenotypic markers (including maturation and homing markers and pattern recognition receptors) and on-going DC cytokine production during 4 hours’ culture were assessed.

Results Production of TNFα by myeloid DC was significantly reduced (p = 0.016 Fig C) in those patients who received vitamin D alongside anti-TNFα therapy; without vitamin D treatment, TNFα production by myeloid DC did not decrease significantly after anti-TNFα therapy (p = 0.96 Fig B). There was a significant negative correlation between change in vitamin D level and change in TNFα production by myeloid DC (p = 0.025, correlation coefficient =0.68 Fig D). An increase of serum 25(OH)vitamin D greater than 20 nmol/m was associated with a decrease in myeloid DC TNFα production. Anti-TNFα therapy alone induced a significant upregulation of the skin homing marker cutaneous lymphocyte antigen (CLA) on myeloid DC (p = 0.0055), an effect which was not seen in patients receiving adjunctive vitamin D.

Abstract PWE-023 Figure 1

A&B TNFα production by mDC before and after treatment with anti-TNFα therapy in: patients who did not (A) and patients who did (B) receive vitamin D. (C) Correlation of change in vitamin D level and decrease in TNFα production by mDC

Conclusion High doses of parenteral vitamin D in patients with Crohn’s promotes anti-TNFα down-regulation of circulating myeloid DC production of TNFα which may influence the subsequent interaction of DC and T cells. TNFα promotes a TH-1/ TH-17 response characteristic of Crohn’s inflammation; thus the ability of vitamin D to further block TNFα production may promote a more regulatory T cell response and improve outcomes when used as an adjunct to anti-TNFα therapy. The down-regulation of skin homing marker CLA by vitamin D may be clinically useful in those patients suffering cutaneous sequelae of anti-TNFα therapy.

Disclosure of Interest None Declared

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