title: Elevated serum levels of B-cell activating factor in pediatric renal transplant patients.
abstract: BACKGROUND
  B-cells are increasingly recognized as important players in alloimmunity. B cell-activating factor (BAFF) and its receptor BAFF-R are essential for B-cell differentiation and survival. Data on BAFF levels in pediatric renal transplant (RT) patients are scarce.
  
  
  OBJECTIVE
  It is known from adult data that elevated BAFF levels correlate with an unfavorable outcome in bone marrow and kidney recipients. To analyze this hypothesis in pediatric renal transplant patients we performed a cross-sectional analysis of serum BAFF levels, lymphocyte surface BAFF-R expression, and clinical variables in a cohort of 43 pediatric renal transplant patients.
  
  
  METHODS
  We studied serum BAFF, CD19+ B-, and FoxP3+ regulatory T-cells (Tregs) and BAFF-R expression in 43 children 2.9 (0.1-12.4) years after RT on maintenance immunosuppression. Twenty-two healthy children and 19 children with chronic kidney disease stage 5 (CKD5) served as controls.
  
  
  RESULTS
  BAFF levels were significantly higher in RT patients than in healthy children (1,435±574 vs 894±189 pg/mL; p<0.0001) whereas numbers of B-cells and Tregs were significantly lower. BAFF-R expression on B-cells was decreased after RT (531±334 vs 707±257 MFI; p<0.005), BAFF inversely correlated with BAFF-R (r=-0.5022, p<0.006), but not with B-cell count. BAFF was elevated in CKD5 patients (1,276±294 pg/mL). In RT patients BAFF was significantly higher in those with eGFR <60 ml/min/1.73m(2) (1,553±447 vs 1,234±323 pg/mL; p=0.02). BAFF levels and BAFF-R expression did not correlate with HLA antibody status, time after transplantation, age or gender of the patients.
  
  
  CONCLUSIONS
  Serum BAFF concentrations were significantly elevated in pediatric RT patients. They correlated with decreased BAFF-R expression on CD19+ B-cells and impaired allograft function. Our findings of a dysregulated BAFF/BAFF-R axis may be of clinical relevance after renal transplantation and therefore underline the importance of further research into BAFF-dependent mechanisms.
authors.affiliation: University Medical Center Hamburg-Eppendorf, Pediatric Nephrology, Martinistrasse 52, 20246 Hamburg, Germany. a.lehnhardt@uke.de
authors.forename: Anja
authors.initials: A
authors.lastname: Lehnhardt
authors.forename: Franziska
authors.initials: F
authors.lastname: Dunst
authors.forename: Michael
authors.initials: M
authors.lastname: van Husen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Loos
authors.forename: Jun
authors.initials: J
authors.lastname: Oh
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiermann
authors.forename: Martina
authors.initials: M
authors.lastname: Koch
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Kemper
mesh_terms: D000293:Adolescent; D053264:B-Cell Activating Factor / Q000097:blood*; D053265:B-Cell Activation Factor Receptor / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C435926:TNFRSF13C protein, human