title: Peripheral Blood CD38 Bright CD8+ Effector Memory T Cells Predict Acute Graft-versus-Host Disease.
abstract: Acute graft-versus-host disease (aGVHD) is mediated by allogeneic T cell responses. We hypothesized that increases of peripheral blood-activated CD8+ effector memory T (TEM) cells would be observed after hematopoietic stem cell transplantation (HSCT) before onset of aGVHD symptoms. Blood was collected twice weekly after HSCT for 7 weeks in 49 consecutive pediatric and adult HSCT recipients. Samples were incubated with fluorochrome-conjugated antibodies against CD45, CD3, CD8, CD38, CD45RA, and CCR7 and analyzed using flow cytometry. TEM cells were defined as CD3+ CD8+ CCR7- CD45RA(-) lymphocytes. CD38 expression was used as a marker of T cell activation. Patients were followed for 100 days for development of aGVHD. Twenty-three patients developed grade 1 to 4 aGVHD at a median of 37 days (range, 15 to 79 days) after HCST. Absolute CD38 bright CD8+ TEM of > 35 cells/μL predicted aGVHD at a median of 8 days (range, 1 to 34) before aGVHD onset with a sensitivity of 82.6% and specificity of 91.6%. The cumulative incidence of aGVHD was 90% in patients with absolute CD38 bright CD8+ TEM >35 cells/μL and 15% in patients without (P < .0001). Quantification of CD38 bright CD8+ TEM cells may predict aGVHD in children and young adult HSCT recipients.
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Pooja.khandelwal@cchmc.org.
authors.forename: Pooja
authors.initials: P
authors.lastname: Khandelwal
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Adam
authors.initials: A
authors.lastname: Lane
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Chaturvedi
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Erika
authors.initials: E
authors.lastname: Owsley
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.affiliation: Cancer and Blood Diseases Institute Laboratory, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Daniel
authors.initials: D
authors.lastname: Marmer
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jordan
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000276:immunology*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006650:Histocompatibility Testing; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D019653:Myeloablative Agonists; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
keywords: CD38 bright CD8(+) effector memory T cells (TEMs); Effector memory T cells; Graft-versus-host disease (GVHD) predictive biomarker