Altered immune reconstitution of B and T cells precedes the onset of clinical symptoms of chronic graft-versus-host disease and is influenced by the type of onset
Altered immune reconstitution of B and T cells precedes the onset of clinical symptoms of chronic graft-versus-host disease and is influenced by the type of onset
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DOI：
10.1007/s00277-016-2881-x
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发表时间：
2017-02-01
影响因子：
3.5
通讯作者：
Wolff, D.
中科院分区：
文献类型：
--
作者：
Bohmann, E. -M.;Fehn, U.;Wolff, D.
我们分析了异基因造血干细胞移植后3个月的淋巴细胞亚群和细胞因子，旨在确定慢性移植物抗宿主病（cGVHD）的预测细胞和血清标志物。通过流式细胞术和酶联免疫吸附测定，在不存在活动性GVHD的情况下分析了49名患者（pts）（无cGVHD（n = 14），随后静止发作（n = 16），新发cGVHD（n = 19））的样品。所有平均绝对细胞计数以每微升细胞数表示;相对细胞计数以淋巴细胞百分比表示。随后新发cGVHD患者的CD 4 + T细胞相对和绝对计数显著较高，包括CD 4+记忆T细胞绝对计数较高（分别为22.36%; 206.55/mu l; 136/mu l），与随后发生cGVHD的患者相比（12.41%; 83.42/μ l; 54.3/μ l）和无cGVHD的患者（10.55%）关于CD 4 + T细胞的相对计数。同样，与未发生cGVHD（1.25%和9.06/μ l）或静止期发生cGVHD（1.15%和6.91/μ l）的患者相比，在新发cGVHD（3.08%和24.63/μ l）患者中检测到显著更多的相对和绝对调节性T细胞数（CD 4 + FOXP 3+）。最后，相对B细胞计数，包括幼稚和记忆B细胞，在发展静止期cGVHD的患者中也显著降低（分别为0.85、0.73、0.12%）。与新发患者相比（5.61，5.24，0.38%）。结果表明，免疫重建的改变在临床症状发作之前就已经存在，并且在疾病的新发和静止发作之间存在差异。
We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes. Pts with subsequent de novo cGVHD had significantly higher relative and absolute counts of CD4+ T cells including higher absolute counts of CD4+ memory T cells (22.36%; 206.55/mu l; 136/mu l, respectively) compared to pts with subsequent quiescent onset of cGVHD (12.41%; 83.42/mu l; 54.3/mu l) and pts without cGVHD (10.55%) with regard to relative counts of CD4+ T cells. Similarly, significantly more relative and absolute regulatory T cell numbers (CD4+FOXP3+) were detected in pts with de novo onset of cGVHD (3.08% and 24.63/mu l) compared to those in pts without (1.25% and 9.06/mu l) or with quiescent onset of cGVHD (1.15% and 6.91/mu l). Finally, relative B cell counts, including na < ve and memory B cells, were also significantly decreased in pts developing quiescent cGVHD (0.85, 0.73, 0.12% resp.) when compared to pts with de novo onset (5.61, 5.24, 0.38%). The results demonstrate that alterations in immune reconstitution are already present before onset of clinical symptoms and differ between de novo and quiescent onset of disease.