title: B-cell activating factor (BAFF) is elevated in chronic granulomatous disease.
abstract: Chronic Granulomatous Disease (CGD) is an inherited defect in superoxide production leading to life-threatening infections, granulomas, and, possibly, abnormal immunoglobulin concentrations. We investigated whether factors controlling antibody production, such as B-cell activating factor (BAFF), were altered in CGD. CGD subjects had significantly increased mean (2.3-fold, p < 0.0001) plasma concentrations of BAFF compared to healthy donors. Patients on IFN-γ treatment had significantly higher BAFF concentrations compared with CGD patients not taking IFN-γ (1.6-fold, p < 0.005). Leukocytes from CGD subjects produced normal amounts of BAFF in response to IFN-γ or G-CSF in vitro. Expression of BAFF-R and TACI was significantly reduced on CGD B cells. Elevated BAFF in CGD correlated with CRP (R = 0.44), ESR (R = 0.49), and IgM (R = 0.47) and increased rapidly in healthy subjects following intravenous endotoxin administration. These findings suggest that elevated BAFF in CGD subjects and healthy donors is a consequence of acute and chronic inflammation.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kabir
authors.initials: K
authors.lastname: Matharu
authors.forename: Kol A
authors.initials: KA
authors.lastname: Zarember
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Marciano
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kuhns
authors.forename: Christine
authors.initials: C
authors.lastname: Spalding
authors.forename: Mary
authors.initials: M
authors.lastname: Garofalo
authors.forename: Thomas
authors.initials: T
authors.lastname: Dimaggio
authors.forename: Tyra
authors.initials: T
authors.lastname: Estwick
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Danielle
authors.initials: D
authors.lastname: Fink
authors.forename: Debra L
authors.initials: DL
authors.lastname: Priel
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.forename: John I
authors.initials: JI
authors.lastname: Gallin
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging; D053264:B-Cell Activating Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D007378:Interleukins / Q000097:blood; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; D004731:Endotoxins; D007378:Interleukins; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D000098546:Interleukin-21
keywords: B cell activating factor; B cell receptor; B-cell activating factor; BAFF; BCR; CGD; Chronic Granulomatous Disease; Inflammation; TACI; transmembrane activator and CAML-interactor.