title: C3d plasma levels and CD21 expressing B-cells in children after ABO-incompatible heart transplantation: Alterations associated with blood group tolerance.
abstract: BACKGROUND
  Most children transplanted with ABO-incompatible (ABOi) hearts develop selective tolerance to donor A/B antigens, whereas anti-A/B antibodies typically re-accumulate in adults after ABOi kidney transplantation. Deficiency of essential factors linking innate and adaptive immunity in early childhood may promote development of tolerance, specifically interactions between complement split product C3d and its ligand CD21 on B cells, considering their role in augmenting "T-independent" B-cell activation.
  
  
  METHODS
  Blood and clinical data were analyzed from children after ABOi or ABO-compatible (ABOc) heart transplantation (HTx). Plasma C3d levels were quantified by enzyme-linked immunoassay. Peripheral blood mononuclear cells (PBMC) were phenotyped by flow cytometry; expression of B-cell co-receptor components CD21 and CD81 was quantified.
  
  
  RESULTS
  Fifty-five samples from pediatric HTx recipients (median age at transplant: 4.2 [range 0.03 to 20.4] months; age at sample collection: 14.6 [0.04 to 51.3] months; 53% ABOi) and 21 controls were studied. CD21-expressing B cells increased in trend with age (p = 0.079); longitudinal measures in individual patients showed a strong correlation with age. CD21 expression intensity in B-cells was not age-dependent. Plasma C3d levels did not correlate with age. Comparing ABOc vs ABOi HTx, CD21-expressing cell proportions were similar; however, serum C3d levels were significantly lower after ABOi HTx (p < 0.05).
  
  
  CONCLUSIONS
  In children, including HTx patients, CD21-expressing B-cells show a trend to increase with age, corresponding with improved responsiveness to polysaccharide antigens. This does not differ in patients with ABOi grafts developing tolerance to donor ABO antigens. C3d levels are not age-dependent, but reduced C3d levels after ABOi HTx suggest altered complement metabolism contributing to ABO tolerance.
authors: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: urschel@ualberta.ca.
authors: Simon
authors: S
authors: Urschel
authors: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors: Lauren A
authors: LA
authors: Ryan
authors: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors: Ingrid M
authors: IM
authors: Larsen
authors: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors: Kim
authors: K
authors: Derkatz
authors: Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Ivan M
authors: IM
authors: Rebeyka
authors: Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: David B
authors: DB
authors: Ross
authors: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Lori J
authors: LJ
authors: West
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000097:blood* / Q000276:immunology*; D015933:Complement C3d / Q000032:analysis*; D016027:Heart Transplantation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007223:Infant; D011446:Prospective Studies; D017464:Receptors, Complement 3d / Q000276:immunology*
chemical_list: D000017:ABO Blood-Group System; D017464:Receptors, Complement 3d; D015933:Complement C3d
keywords: ABO; B-cell co-receptor; blood group incompatible transplant; complement; immune maturation and development; pediatric heart transplantation; tolerance