Longitudinal analysis of T-cell receptor variable β chain repertoire in patients with acute graft-versus-host disease after allogeneic stem cell transplantation
Longitudinal analysis of T-cell receptor variable β chain repertoire in patients with acute graft-versus-host disease after allogeneic stem cell transplantation
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DOI：
10.1016/j.bbmt.2005.09.019
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发表时间：
2006-03-01
影响因子：
4.3
通讯作者：
Chao, NJ
中科院分区：
文献类型：
--
作者：
Liu, CX;Me, H;Chao, NJ
t细胞受体可变β链（TCRBV）库谱分型包括用于监测t细胞受体多样性的CDR3长度分布的估计，并且已被证明可用于分析同种异体干细胞移植后移植物抗宿主病（GVHD）和移植物抗白血病的免疫重建和t细胞克隆扩增。我们对28例接受同种异体T细胞耗尽外周血干细胞移植的患者的23个TCRBV家族进行了纵向谱型分析。16例患者随后发展为急性GVHD。我们最近开发的统计方法为谱型分析带来了更大的能力和灵活性，并允许我们在适当复杂的统计模型下分析TCRBV库的发展。应用这些方法，我们发现急性GVHD患者的TCRBV库发展与非GVHD患者的TCRBV库发展有统计学差异。具体而言，GVHD患者的谱型多样性较低，与健康个体的谱型偏差较大。在移植后6个月，大多数个体TCRBV亚家族在GVHD和非GVHD患者之间具有统计学意义上的谱型。这些结果表明，与急性GVHD相关的t细胞受体库紊乱在TCRBV家族中广泛传播。(C) 2006年美国血液和骨髓移植学会。
T-cell receptor variable beta chain (TCRBV) repertoire spectratyping involves the estimation of CDR3 length distributions for monitoring T-cell receptor diversity and has proven useful for analyses of immune reconstitution and T-cell clonal expansions in graft-versus-host disease (GVHD) and graft-versus-leukemia after allogeneic stem cell transplantation. We performed a longitudinal spectratype analysis of 23 TCRBV families in 28 patients who underwent allogeneic T cell-depleted peripheral blood stem cell transplantation. Sixteen patients subsequently developed acute GVHD. We recently developed statistical methods that bring increased power and flexibility to spectratype analysis and allow us to analyze TCRBV repertoire development under appropriately complex statistical models. Applying these methods, We found that patients with acute GVHD demonstrated TCRBV repertoire development statistically distinct from that repertoire development in patients without GVHD. Specifically, GVHD patients showed spectratypes indicative of lower diversity and greater deviation from the spectratypes expected in health), individuals at intermediate times. Most individual TCRBV subfamilies had spectratypes statistically, distinguishable between GVHD and non-GVHD patients at 6 months after transplantation. These results suggest that the T-cell receptor repertoire perturbations associated with acute GVHD are widely spread throughout the TCRBV families. (C) 2006 American Society for Blood and Marrow Transplantation.