Biologic markers of chronic GVHD.

Biologic markers of chronic GVHD.
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DOI:
10.1038/bmt.2013.97
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发表时间:
2014-03
影响因子:
4.8
通讯作者:
Lee, S. J.
Lee, S. J.
中科院分区:
医学3区
文献类型:
--
作者:
Pidala, J.;Sarwal, M.;Roedder, S.;Lee, S. J.

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慢性移植物抗宿主病(GVHD)的生物标志物可能提供对该综合征发病机制的洞察,为新的干预措施确定分子靶点,并促进临床治疗的进步。尽管到目前为止开展的大量工作主要集中在对该综合征的预测和诊断上,但很少对研究结果进行综合,并在独立人群中对有希望的候选标记进行验证。研究表明,移植后慢性移植物抗宿主病的风险可能与供受者基因多态性、调节性免疫细胞群(NK、Treg、DC2)缺乏以及移植后炎症和免疫调节介质的变化(肿瘤坏死因子α、IL-10和BAFF升高,转化生长因子β和IL-15降低)有关。慢性移植物抗宿主病的建立与免疫细胞群的改变有关(CD3+T细胞、Th17、CD4+和CD8+效应记忆细胞、单核细胞、CD86表达、BAFF/B细胞比率、Treg、NK细胞和幼稚CD8+T细胞缺乏)。炎症和免疫调节因子(肿瘤坏死因子α、IL-6、IL-1β、IL-8、sIL-2R和IL-1ra、bAFF、抗双链DNA、sIL-2Rα和sCD13)也受到干扰。对慢性移植物抗宿主病的表型和严重程度、治疗反应和预后的生物学标志物知之甚少。
Biologic markers of chronic graft vs. host disease (GVHD) may provide insight into the pathogenesis of the syndrome, identify molecular targets for novel interventions, and facilitate advances in clinical management. Despite extensive work performed to date largely focused on prediction and diagnosis of the syndrome, little synthesis of findings and validation of promising candidate markers in independent populations has been performed. Studies suggest that risk for subsequent chronic GVHD development may be associated with donor-recipient genetic polymorphism, deficiency in regulatory immune cell populations (NK, Treg, DC2), and variation in inflammatory and immunoregulatory mediators post-HCT (increased TNFα, IL-10 and BAFF, and decreased TGFβ and IL-15). Established chronic GVHD is associated with alteration in immune cell populations (increased CD3+ T cells, Th17, CD4+ and CD8+ effector memory cells, monocytes, CD86 expression, BAFF/B cell ratio, and deficiency of Treg, NK cells, and naïve CD8+ T cells). Inflammatory and immunomodulatory factors (TNFα, IL-6, IL-1β, IL-8, sIL-2R, and IL-1Ra, BAFF, anti-dsDNA, sIL-2Rα, and sCD13) are also perturbed. Little is known about biologic markers of chronic GVHD phenotype and severity, response to therapy, and prognosis.
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