title: CD19+CD21low B cells and CD4+CD45RA+CD31+ T cells correlate with first diagnosis of chronic graft-versus-host disease.
abstract: Chronic graft-versus-host disease (cGVHD) is a serious and frequent complication of allogeneic hematopoietic stem cell transplantation (HCT). Currently, no biomarkers for prediction and diagnosis of cGVHD are available. We performed a large prospective study focusing on noninvasive biomarkers for National Institutes of Health-defined cGVHD patients (n = 163) in comparison to time-matched HCT recipients who never experienced cGVHD (n = 64), analyzed from day 100 after HCT. In logistic regression analysis, CD19(+)CD21(low) B cells (P = .002; hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.53 to 7.17) and CD4(+)CD45RA(+)CD31(+) T cells (P < .001; HR, 3.88; 95% CI, 1.88 to 7.99) assessed on day 100 after HCT were significantly associated with subsequent development of cGVHD, independent of clinical parameters. A significant association with diagnosis of cGVHD was only observed for CD19(+)CD21(low) B cells (P = .008; HR, 3.00; 95% CI, 1.33 to 6.75) and CD4(+)CD45RA(+)CD31(+) T cells (P = .017; HR, 2.80; 95% CI, 1.19 to 6.55). CD19(+)CD21(low) B cells were found to have the highest discriminatory value with an area under the receiver operating curve of .77 (95% CI, .64 to .90). Our results demonstrate that CD19(+)CD21(low) B cells and CD4(+)CD45RA(+)CD31(+) T cells are significantly elevated in patients with newly diagnosed cGVHD.
authors.affiliation: Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria. Electronic address: hildegard.greinix@meduniwien.ac.at.
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
authors.affiliation: Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Kuzmina
authors.affiliation: Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
authors.forename: Roman
authors.initials: R
authors.lastname: Weigl
authors.affiliation: Institute of Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Körmoczi
authors.affiliation: Institute of Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Arno
authors.initials: A
authors.lastname: Rottal
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.affiliation: Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
authors.forename: Mateja
authors.initials: M
authors.lastname: Kralj
authors.affiliation: Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Kalhs
authors.affiliation: Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Mitterbauer
authors.affiliation: Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Rabitsch
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Edinger
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.affiliation: Institute of Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D019337:Hematologic Neoplasms / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D016015:Logistic Models; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D015415:Biomarkers
keywords: B cells; Biomarker; Chronic graft-versus-host disease