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O型血创伤患者表现出独特的多组学特征,补体凝集素途径水平降低。

Trauma patients with type O blood exhibit unique multiomics signature with decreased lectin pathway of complement levels.

作者信息

Stocker Benjamin W, LaCroix Ian S, Erickson Christopher, Gallagher Lauren T, Ramser Benjamin J, Thielen Otto, Hallas William, Mitra Sanchayita, Moore Ernest E, Hansen Kirk, D'Alessandro Angelo, Silliman Christopher C, Cohen Mitchell J

机构信息

From the Department of Surgery (B.W.S., L.T.G., B.J.R., O.T., W.H., S.M., E.E.M., C.C.S., M.J.C.), and Department of Biochemistry and Molecular Genetics (I.S.L., C.E., K.H., A.D.), School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; Department of Surgery (E.E.M.), Ernest E Moore Shock Trauma Center, Denver Health Medical Center; Vitalant Research Institute (C.C.S.), Denver; and Department of Pediatrics (C.C.S.), School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

出版信息

J Trauma Acute Care Surg. 2024 Nov 1;97(5):753-763. doi: 10.1097/TA.0000000000004367. Epub 2024 May 15.

Abstract

BACKGROUND

Patients with type O blood may have an increased risk of hemorrhagic complications because of lower baseline levels of von Willebrand factor and factor VIII, but the transition to a mortality difference in trauma is less clear. We hypothesized that type O trauma patients will have differential proteomic and metabolomic signatures in response to trauma beyond von Willebrand factor and factor VIII alone.

METHODS

Patients meeting the highest level of trauma activation criteria were prospectively enrolled. Blood samples were collected upon arrival to the emergency department. Proteomic and metabolomic (multiomics) analyses of these samples were performed using liquid chromatography-mass spectrometry. Demographic, clinical, and multiomics data were compared between patients with type O blood versus all other patients.

RESULTS

There were 288 patients with multiomics data; 146 (51%) had type O blood. Demographics, injury patterns, and initial vital signs and laboratory measurements were not different between groups. Type O patients had increased lengths of stay (7 vs. 6 days, p = 0.041) and a trend toward decreased mortality secondary to traumatic brain injury compared with other causes (traumatic brain injury, 44.4% vs. 87.5%; p = 0.055). Type O patients had decreased levels of mannose-binding lectin and mannose-binding lectin-associated serine proteases 1 and 2, which are required for the initiation of the lectin pathway of complement activation. Type O patients also had metabolite differences signifying energy metabolism and mitochondrial dysfunction.

CONCLUSION

Blood type O patients have a unique multiomics signature, including decreased levels of proteins required to activate the lectin complement pathway. This may lead to overall decreased levels of complement activation and decreased systemic inflammation in the acute phase, possibly leading to a survival advantage, especially in traumatic brain injury. However, this may later impair healing. Future work will need to confirm these associations, and animal studies are needed to test therapeutic targets.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.

摘要

背景

由于血管性血友病因子和凝血因子 VIII 的基线水平较低,O 型血患者可能有出血并发症风险增加的情况,但在创伤中转变为死亡率差异的情况尚不清楚。我们假设 O 型创伤患者除了血管性血友病因子和凝血因子 VIII 外,对创伤的蛋白质组学和代谢组学特征也会有所不同。

方法

前瞻性纳入符合最高级别创伤激活标准的患者。患者抵达急诊科时采集血样。使用液相色谱 - 质谱法对这些样本进行蛋白质组学和代谢组学(多组学)分析。比较 O 型血患者与所有其他患者的人口统计学、临床和多组学数据。

结果

有 288 例患者有多组学数据;146 例(51%)为 O 型血。两组之间的人口统计学、损伤模式、初始生命体征和实验室测量结果无差异。与其他原因相比,O 型血患者住院时间延长(7 天对 6 天,p = 0.041),继发于创伤性脑损伤的死亡率有降低趋势(创伤性脑损伤,44.4%对 87.5%;p = 0.055)。O 型血患者甘露糖结合凝集素以及补体激活凝集素途径起始所需的甘露糖结合凝集素相关丝氨酸蛋白酶 1 和 2 的水平降低。O 型血患者还存在表明能量代谢和线粒体功能障碍的代谢物差异。

结论

O 型血患者具有独特的多组学特征,包括激活凝集素补体途径所需蛋白质水平降低。这可能导致急性期补体激活总体水平降低和全身炎症反应减轻,可能带来生存优势,尤其是在创伤性脑损伤中。然而,这可能随后会损害愈合。未来的研究需要证实这些关联,并且需要动物研究来测试治疗靶点。

证据水平

预后和流行病学;IV 级。

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