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Lower levels of vitamin A are associated with increased gastrointestinal graft versus host disease in children

Dana T. Lounder, Pooja Khandelwal, Christopher Dandoy, Sonata Jodele, Michael Grimley, Gregory Wallace, Adam Lane, Cynthia Taggart, Ashley Teusink-Cross, Kelly Lake and Stella M. Davies

Key points

  • Vitamin A levels below the median at day +30 post-transplant are associated with increased cumulative incidence of GI GVHD in children.

  • Potential mechanisms include increased intestinal permeability and increased lymphocyte homing to the intestine.

Abstract

Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce risk of graft versus host disease through reduced intestinal permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 post-transplant. GI GVHD was increased in patients with vitamin A levels below the median (38% vs 12.4% at 100 days, p=0.0008), as was treatment-related mortality (17.7% vs 7.4% at 1 year, p=0.03). Blood stream infections were increased in patients with vitamin A levels below the median (24% vs 8% at 1 year, p=0.03), supporting our hypothesis of increased intestinal permeability. The GI mucosal protein I-FABP was decreased after transplant, confirming mucosal injury, but was not correlated with vitamin A levels, indicating that vitamin A did not protect against mucosal injury. Expression of the gut homing receptor CCR9 on T-effector memory cells 30 days after transplant was increased in children with vitamin A levels below the median (r= -0.34, p=0.03). Taken together, these data support our hypothesis that low levels of vitamin A actively promote GI GVHD, and are not simply a marker of poor nutritional status or a sicker patient. Vitamin A supplementation might improve transplant outcomes.

  • Submitted February 1, 2017.
  • Accepted March 3, 2017.