title: Relative defects in mucosal immunity predict acute graft-versus-host disease.
abstract: Impairment of gut mucosal immunity by the transplant process could facilitate translocation of commensal bacteria and thereby augment the graft-versus-host response. To begin to assess the influence of gut mucosal immunity on the development of acute graft-versus-host disease (GVHD), we conducted a prospective study in 24 pediatric allogeneic hematopoietic cell transplant recipients, assessing 4 fecal markers of mucosal immunity: calprotectin, soluble CD8 (sCD8), soluble intracellular adhesion molecule 1, and β-defensin-2. Stool samples were collected prospectively on transplant days 0, +5, +10, and +15 and analyzed by ELISA. Lower levels on day +5 (calprotectin and β-defensin-2) and day +10 (calprotectin, β-defensin-2, and sCD8) were associated with subsequent acute GVHD. The most striking difference was with calprotectin on day +10. Patients with levels below 424 mg/kg had an incidence of 77.8%, whereas those with levels above this threshold had a cumulative incidence of 0% (P = .002). Relative defects in gut mucosal immunity may be important in the pathogenesis of acute GVHD.
authors.affiliation: Division of Pediatric Hematology-Oncology, Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: August
authors.affiliation: Division of Pediatric Hematology-Oncology, Aflac Cancer and Blood Disorders Center, Emory University/Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: K-Y
authors.initials: KY
authors.lastname: Chiang
authors.affiliation: Division of Pediatric Hematology-Oncology, Aflac Cancer and Blood Disorders Center, Emory University/Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Muna
authors.initials: M
authors.lastname: Qayed
authors.affiliation: Division of Pediatric Hematology-Oncology, Aflac Cancer and Blood Disorders Center, Emory University/Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Ashley
authors.initials: A
authors.lastname: Dulson
authors.affiliation: Division of Pediatric Hematology-Oncology, Aflac Cancer and Blood Disorders Center, Emory University/Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Diana
authors.initials: D
authors.lastname: Worthington-White
authors.affiliation: Division of Pediatric Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Conrad R
authors.initials: CR
authors.lastname: Cole
authors.affiliation: Division of Pediatric Hematology-Oncology, Aflac Cancer and Blood Disorders Center, Emory University/Children's Healthcare of Atlanta, Atlanta, Georgia. Electronic address: jth2148@columbia.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Horan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D018928:Immunity, Mucosal; D007223:Infant; D008297:Male; D014184:Transplantation, Homologous; D055815:Young Adult
keywords: Allogeneic hematopoietic cell transplantation; Fecal biomarkers; Graft-versus-host disease; Gut mucosal immunity