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Title: Plasma markers of B-cell activation and clonality in pediatric liver and hematopoietic stem cell transplant recipients.
Authors: Engels EA,  Savoldo B,  Pfeiffer RM,  Costello R,  Zingone A,  Heslop HE,  Landgren O
Journal: Transplantation
Date: 2013 Feb 15
Branches: BB, IIB
PubMed ID: 23222884
PMC ID: PMC3566275
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.