Plasma markers of B-cell activation and clonality in pediatric liver and hematopoietic stem cell transplant recipients

Transplantation. 2013 Feb 15;95(3):519-26. doi: 10.1097/TP.0b013e318274ab63.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • B-Lymphocytes / pathology*
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Herpesvirus 4, Human*
  • Humans
  • Immunoglobulin Light Chains / blood*
  • Immunoglobulin kappa-Chains / blood
  • Immunoglobulin lambda-Chains / blood
  • Infant
  • Ki-1 Antigen / blood*
  • Liver Transplantation* / pathology
  • Lymphocyte Activation / physiology*
  • Lymphoproliferative Disorders / epidemiology
  • Male
  • Retrospective Studies
  • Risk Factors
  • Transplantation
  • Viral Load
  • Viral Matrix Proteins / blood*
  • Virus Replication / physiology
  • Young Adult


  • Biomarkers
  • Immunoglobulin Light Chains
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Ki-1 Antigen
  • Viral Matrix Proteins