title: CD19(+)CD21(low) B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome.
abstract: Bronchiolitis obliterans syndrome (BOS), pathognomonic for chronic graft-versus-host disease (cGVHD) of the lung, is a progressive and often fatal complication after allogeneic hematopoietic cell transplantation (HCT). Biomarkers for the prediction and diagnosis of BOS are urgently needed to improve patients' prognosis. We prospectively evaluated B-cell subpopulations and B-cell activating factor (BAFF) in 136 patients (46 BOS, 41 no cGVHD, 49 cutaneous cGVHD) to define novel biomarkers for early diagnosis of National Institutes of Health-defined BOS diagnosed a median of 11 mo after HCT. Patients with newly diagnosed BOS had significantly higher percentages of CD19(+)CD21(low) B cells (25.5 versus 6.6%, P < .0001), BAFF (7.3 versus 3.5 ng/mL, P = .02), and BAFF/CD19(+) ratio (0.18 versus 0.02 ng/10(3) CD19(+) B cells, P 5 .007) compared with patients without cGVHD. The area under the receiver operating curve for CD19(+)CD21(low) B cells was 0.97 (95% confidence interval, 0.94-0.99) and a cutoff point >9% was optimal for diagnosing BOS in patients with first drop of pulmonary function tests with a sensitivity of 96% and a negative predictive value of 94%. Thus, elevated levels of CD19(+)CD21(low) B cells are a potential novel biomarker for HCT patients at risk for developing BOS at an early stage and could allow improvement of patient outcome.
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.forename: Katharina
authors.initials: K
authors.lastname: Krenn
authors.forename: Ventzislav
authors.initials: V
authors.lastname: Petkov
authors.forename: Ulrike
authors.initials: U
authors.lastname: Körmöczi
authors.forename: Roman
authors.initials: R
authors.lastname: Weigl
authors.forename: Arno
authors.initials: A
authors.lastname: Rottal
authors.forename: Peter
authors.initials: P
authors.lastname: Kalhs
authors.forename: Margit
authors.initials: M
authors.lastname: Mitterbauer
authors.forename: Lothar
authors.initials: L
authors.lastname: Ponhold
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dekan
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000378:metabolism*; D053264:B-Cell Activating Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001989:Bronchiolitis Obliterans / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D017464:Receptors, Complement 3d / Q000378:metabolism*; D015996:Survival Rate; D014184:Transplantation, Homologous; D014481:United States; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D053264:B-Cell Activating Factor; D014408:Biomarkers, Tumor; D017464:Receptors, Complement 3d; C505719:TNFSF13B protein, human