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

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

Eric A Engels  1 , Barbara Savoldo, Ruth M Pfeiffer, Rene Costello, Adriana Zingone, Helen E Heslop, Ola Landgren
Affiliations

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

Eric A Engels et al. Transplantation. .

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.

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Conflict of interest statement

The authors of this manuscript have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Longitudinal measurements of plasma free light chain and EBV loads in five PTLD cases. Results are shown for five transplant recipients who developed PTLD and who had at least one plasma sample that manifested a monoclonal pattern of free light chain elevation. A monoclonal pattern is present when at least one free light chain is above the upper limit of normal and the kappa:lambda ratio is abnormal. Results are shown for kappa (squares) and lambda (circles), according to multiples of the upper limit of normal (left axis). Sold symbols represent observations for which a monoclonal FLC pattern was present, and open symbols when a monoclonal FLC pattern was absent. The EBV load is shown as a dashed line with X symbols, using a logarithmic scale (right axis). The PTLD diagnosis date is shown with a vertical line. The panels also include information about the transplant (liver vs. hematopoietic stem cell transplant) and type of PTLD. Note that the time scale differs across panels
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