title: Plasma markers of B-cell activation and clonality in pediatric liver and hematopoietic stem cell transplant recipients.
abstract: BACKGROUND
  Transplant recipients are at risk of posttransplant lymphoproliferative disease (PTLD).
  
  
  METHODS
  Thirty-six pediatric transplant recipients were evaluated (18 hematopoietic stem cell and 18 liver recipients; 12 had PTLD). We studied 207 longitudinal plasma samples from these recipients for three markers of B-cell activation or clonality: immunoglobulin free light chains (FLCs), soluble CD30 (sCD30), and monoclonal immunoglobulins (M-proteins).
  
  
  RESULTS
  Kappa FLCs, lambda FLCs, and sCD30 were elevated in 20.8%, 28.0%, and 94.2% of plasma specimens, respectively. Free light chain and sCD30 levels increased significantly 1.18 to 1.82 fold per log10 Epstein-Barr virus (EBV) load in peripheral blood. Five PTLD cases manifested elevated FLCs with an abnormal kappa/lambda ratio, suggesting monoclonal FLC production. M-proteins were present in 91% of PTLD cases versus 50% to 67% of other recipients with high or low EBV loads (P=0.13). Concordance of FLCs, M-proteins, and PTLD tumor light chain restriction was imperfect. For example, one PTLD case with an IgG lambda M-protein had a tumor that was kappa restricted, and another case with an M-protein had a T-cell PTLD. In an additional case, an IgM kappa M-protein and excess kappa FLCs were both detected in plasma at PTLD diagnosis; although the tumor was not restricted at diagnosis, kappa restriction was present 5 years later when the PTLD relapsed.
  
  
  CONCLUSIONS
  Plasma markers of B-cell dysfunction are frequent after transplantation and associated with poor EBV control. These abnormal markers may be produced by oligoclonal B-cell populations or PTLD tumor cells and could potentially help identify recipients at high risk of PTLD.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA. engelse@exchange.nih.gov
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Rene
authors.initials: R
authors.lastname: Costello
authors.forename: Adriana
authors.initials: A
authors.lastname: Zingone
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D007223:Infant; D017730:Ki-1 Antigen / Q000097:blood*; D016031:Liver Transplantation / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D008232:Lymphoproliferative Disorders / Q000453:epidemiology; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D014180:Transplantation; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000097:blood*; D014779:Virus Replication / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D017730:Ki-1 Antigen; D014763:Viral Matrix Proteins