Department of Anesthesia and Intensive Care Medicine, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Front Immunol. 2023 Mar 29;14:1044444. doi: 10.3389/fimmu.2023.1044444. eCollection 2023.
Pancreas transplant alone (PTA) recipients are more affected by pancreas graft thrombosis, and graft loss compared to simultaneous pancreas-kidney (SPK) recipients. The pathophysiology is unknown, but an increased immune response has been suggested in the PTA recipients. In this observational study, we compared perioperative thromboinflammation between PTA (n=32) and SPK (n=35) recipients, and between PTA recipients with (n=14) versus without (n=18) early graft thrombosis.
We measured C-reactive protein (CRP), plasma markers of activated coagulation and complement, and cytokines preoperatively and daily during the first postoperative week.
Preoperatively, coagulation and complement activation markers were comparable between PTA and SPK recipients, while cytokine concentrations were higher in SPK recipients (TNF, IL-8, IP-10, MCP-1, MIP-1α; all <0.05). On the first postoperative day, PTA recipients had higher coagulation activation, measured as thrombin-antithrombin complex (TAT), than SPK recipients (=0.008). In the first postoperative week, PTA recipients showed higher relative cytokine release (IL-6, IL-8, G-CSF, IP-10, MCP-1, and MIP-1α; all <0.05) while SPK recipients showed higher absolute cytokine concentrations (TNF, IL-1ra, IL-8, MIP-1α, and IL-4; all <0.05). PTA and SPK recipients showed similar terminal complement complex (TCC, sC5b-9) activation. On the first postoperative day, TCC (OR 1.2 [95% CI 1.0-1.5] for 0.1 CAU/ml increase, =0.02) and CRP (OR 1.2 [95% CI 1.0-1.3] for 10 mg/L increase, =0.04) were associated with an increased risk of early graft thrombosis. TCC was specific for graft thrombosis, while CRP increased with several complications. PTA recipients with compared to those without graft thrombosis had higher TCC pre- (=0.04) and postoperatively (=0.03).
The relative increase in postoperative thromboinflammatory response was more pronounced in PTA recipients. Complement activation was associated with an increased risk of graft thrombosis. This study indicates that innate immune activation rather than elevated levels may affect early postoperative pancreas graft thrombosis.
https://clinicaltrials.gov/ct2/show/NCT01957696, identifier NCT01957696.
与同时胰腺-肾脏（SPK）移植受者相比，单纯胰腺移植（PTA）受者更容易发生胰腺移植物血栓形成和移植物丢失。其病理生理学尚不清楚，但有人提出 PTA 受者的免疫反应增强。在这项观察性研究中，我们比较了 PTA（n=32）和 SPK（n=35）受者围手术期血栓炎症反应，以及 PTA 受者中（n=14）与无（n=18）早期移植物血栓形成的 PTA 受者之间的血栓炎症反应。
我们在术前和术后第 1 周的每天测量 C 反应蛋白（CRP）、血浆凝血和补体激活标志物以及细胞因子。
术前，PTA 和 SPK 受者的凝血和补体激活标志物无差异，而 SPK 受者的细胞因子浓度更高（TNF、IL-8、IP-10、MCP-1、MIP-1α；均<0.05）。术后第 1 天，PTA 受者的凝血酶-抗凝血酶复合物（TAT）比 SPK 受者高（=0.008）。在术后第 1 周，PTA 受者表现出更高的相对细胞因子释放（IL-6、IL-8、G-CSF、IP-10、MCP-1 和 MIP-1α；均<0.05），而 SPK 受者表现出更高的绝对细胞因子浓度（TNF、IL-1ra、IL-8、MIP-1α 和 IL-4；均<0.05）。PTA 和 SPK 受者的末端补体复合物（TCC，sC5b-9）激活相似。术后第 1 天，TCC（每增加 0.1 CAU/ml，OR 1.2[95%CI 1.0-1.5]，=0.02）和 CRP（每增加 10mg/L，OR 1.2[95%CI 1.0-1.3]，=0.04）与早期移植物血栓形成的风险增加相关。TCC 对移植物血栓形成具有特异性，而 CRP 则与多种并发症相关。与无移植物血栓形成的 PTA 受者相比，有血栓形成的 PTA 受者术前（=0.04）和术后（=0.03）TCC 升高。
PTA 受者术后血栓炎症反应的相对增加更为明显。补体激活与移植物血栓形成风险增加相关。这项研究表明，可能是固有免疫激活而不是细胞因子水平升高影响了术后早期胰腺移植物血栓形成。
https://clinicaltrials.gov/ct2/show/NCT01957696，标识符 NCT01957696。
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