Punyadeera Chamindie, Schneider E Marion, Schaffer Dave, Hsu Hsin-Yun, Joos Thomas O, Kriebel Fabian, Weiss Manfred, Verhaegh Wim Fj
Department of Molecular Diagnostics, Philips Research, High Tech Campus 12a, 5656 AE Eindhoven, The Netherlands, Germany.
J Emerg Trauma Shock. 2010 Jan;3(1):26-35. doi: 10.4103/0974-2700.58666.
In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not.
Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU.
We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1alpha, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1alpha, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1beta and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1alpha and IP-10.
The marker panel is ready to be verified in a validation study with or without therapeutic intervention.
在本研究中,我们报告了初步的研究成果,旨在发现用于鉴别全身炎症反应综合征(SIRS)与脓毒症以及脓毒症不同阶段的潜在生物标志物。此外,我们还研究了是否存在能够区分脓毒症存活患者与非存活患者的蛋白质。
我们的研究组由16名患者组成,其中6人死亡,10人存活。在患者入住重症监护病房(ICU)的整个期间,我们每天检测28种血浆蛋白。
我们观察到金属蛋白酶和可溶性E选择素在区分SIRS和脓毒症中起作用,并且白细胞介素-1α(IL-1α)、干扰素诱导蛋白10(IP-10)、可溶性肿瘤坏死因子受体2(sTNF-R2)和可溶性Fas似乎是脓毒症进展为感染性休克的指标。联合检测基质金属蛋白酶-3(MMP-3)、-10、IL-1α、IP-10、可溶性白细胞介素-2受体(sIL-2R)、可溶性Fas、可溶性肿瘤坏死因子受体1(sTNF-R1)、可溶性晚期糖基化终末产物受体(sRAGE)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-1β和嗜酸性粒细胞趋化因子,能够很好地区分存活患者和死亡患者(死亡率预测的敏感性为79%,特异性为86%)。相关性分析表明IL-1α和IP-10之间存在一种新的相互作用。
该标志物组合已准备好在有或无治疗干预的验证研究中进行验证。