Molecular Analysis of T-Cell Repertoire in Patients with Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation

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Abstract
Complementarity-determining region (CDR3) size spectratyping has often been used to analyze the clonal expansion of T-cells. CDR3 size spectratyping has been useful in the analysis of the oligoclonal expansion of T-cells in virus infection, graft-versus-leukemia effect (GVL), graft-versus-host disease (GVHD), and immune reconstitution of T-cells after allogeneic stem cell transplantation (allo-SCT). We analyzed 26 T cell receptor (TCR)-beta-chain subfamilies (VB) in 25 patients who underwent allo-SCT. Fifteen of these patients developed acute GVHD (aGVHD). Many TCR-VB were skewed in the early stage. In these TCR-VB subfamilies, VB6 was most often skewed at the time of skin aGVHD. We then analyzed the average score of the complexity of 26 TCR-VB spectratypings in patients with or without cGVHD. The patients who developed chronic GVHD (cGVHD) had a lower average score of TCR-VB complexity than that of patients without cGVHD (P = 0.010). In particular. the patients who developed the quiescent type and de novo type of cGVHD from 4 months after allo- SCT had a lower average score of TCR-VB complexity at 3 months than that of the patients who had no cGVHD (P = 0.0055). These results suggest that we might be able to consider a possible development of cGVHD by analyzing TCR-VB spectratyping after allo-SCT.