Atarod Sadaf, Turner Brie, Pearce Kim Frances, Ahmed Shaheda S, Norden Jean, Bogunia-Kubik Katarzyna, Wang Xiao-nong, Collin Matthew, Dickinson Anne Mary
Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Transpl Immunol. 2015 Jun;32(3):188-94. doi: 10.1016/j.trim.2015.02.002. Epub 2015 Feb 11.
Graft-versus-host disease (GVHD) can be a fatal complication of allogeneic stem cell transplantation (allo-HSCT). GVHD can be classified as acute (aGVHD: up to 100 days) or chronic (cGVHD: after 100 days) based on the time-point of disease occurrence. At present there are a limited number of biomarkers available for use in the clinic. Thus, the aim of this research was to evaluate the biomarker potential of the extensively studied Heat Shock Protein 70 family members (HSPA1A/HSPA1B and HSPA1L) at the messenger RNA (mRNA) level in acute and cGVHD patient cohorts. In the skin biopsies, HSPA1L mRNA expression was lower in patients with severe aGVHD (grades II-III) when compared to those with none or low grade aGVHD (grades 0-I) and normal controls. In whole blood, HSPA1L mRNA expression level was significantly (p = 0.008) up-regulated at 28 days post-transplant in cGVHD patients with a significant area under the curve (AUC = 0.773). In addition, HSPA1B expression in whole blood was significantly higher at 3 months post-transplant in both the aGVHD grade II-III (p = 0.012) and cGVHD (p = 0.027) patients. Our initial results in this small cohort show that quantifying HSPA1L mRNA expression in the whole blood of allo-HSCT patients at day 28 post-allo-HSCT may be a useful predictive biomarker for cGVHD.
移植物抗宿主病(GVHD)可能是异基因干细胞移植(allo - HSCT)的致命并发症。根据疾病发生的时间点,GVHD可分为急性(aGVHD:发病至100天)或慢性(cGVHD:发病100天后)。目前临床可用的生物标志物数量有限。因此,本研究的目的是在急性和cGVHD患者队列中,评估广泛研究的热休克蛋白70家族成员(HSPA1A/HSPA1B和HSPA1L)在信使核糖核酸(mRNA)水平上作为生物标志物的潜力。在皮肤活检中,与无aGVHD或轻度aGVHD(0 - I级)患者及正常对照相比,重度aGVHD(II - III级)患者的HSPA1L mRNA表达较低。在全血中,cGVHD患者移植后28天HSPA1L mRNA表达水平显著上调(p = 0.008),曲线下面积显著(AUC = 0.773)。此外,aGVHD II - III级患者(p = 0.012)和cGVHD患者(p = 0.027)移植后3个月全血中的HSPA1B表达均显著升高。我们在这个小队列中的初步结果表明,在allo - HSCT后28天对allo - HSCT患者全血中的HSPA1L mRNA表达进行定量,可能是cGVHD的一种有用的预测生物标志物。