title: Lower levels of vitamin A are associated with increased gastrointestinal graft-versus-host disease in children.
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 the risk of graft-versus-host disease (GVHD) through reduced gastrointestinal (GI) 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 posttransplant. GI GVHD was increased in patients with vitamin A levels below the median (38% vs 12.4% at 100 days,P= .0008), as was treatment-related mortality (17.7% vs 7.4% at 1 year,P= .03). Bloodstream infections were increased in patients with vitamin A levels below the median (24% vs 8% at 1 year,P= .03), supporting our hypothesis of increased intestinal permeability. The GI mucosal intestinal fatty acid-binding protein 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= .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.
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Dana T
authors.initials: DT
authors.lastname: Lounder
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Pooja
authors.initials: P
authors.lastname: Khandelwal
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Dandoy
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Grimley
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Gregory
authors.initials: G
authors.lastname: Wallace
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Adam
authors.initials: A
authors.lastname: Lane
authors.affiliation: Division of Nutrition Therapy, and.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Taggart
authors.affiliation: Department of Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Teusink-Cross
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Lake
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005767:Gastrointestinal Diseases / Q000097:blood*; D006086:Graft vs Host Disease / Q000097:blood*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D015994:Incidence; D007223:Infant; D007413:Intestinal Mucosa / Q000473:pathology; D015999:Multivariate Analysis; D010539:Permeability; D054388:Receptors, CCR / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014801:Vitamin A / Q000097:blood*; D055815:Young Adult
chemical_list: C119309:CC chemokine receptor 9; C101326:RBP4 protein, human; D054388:Receptors, CCR; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A