P44 The CD96-CD155 immune checkpoint axis in ACLF is upregulated and correlates with disease severity
P44 The CD96-CD155 immune checkpoint axis in ACLF is upregulated and correlates with disease severity
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P44 ACLF 中 CD96-CD155 免疫检查点轴上调并与疾病严重程度相关
DOI：
10.1136/gutjnl-2023-basl.60
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Delo J
中科院分区：
文献类型：
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作者：
Delo J
慢性加急性肝功能衰竭（ACLF）是一种以多器官功能衰竭和高短期死亡率为特征的综合征。这种情况代表了一种免疫学悖论，即导致器官功能障碍的猖獗的全身性炎症与免疫细胞功能障碍和对细菌感染的易感性增加并存。因此，了解控制这种平衡的机制至关重要。CD 96是T细胞和NK细胞上表达的免疫检查点，当与其配体CD 155（PVR）结合时，它会传递抑制信号。CD 96和CD 155都有可溶性形式，在其他免疫抑制状态如癌症和慢性病毒感染中发现浓度升高。在这项研究中，我们探讨了CD 96-CD 155免疫检查点轴ACLF.MethodThe外周淋巴细胞膜结合CD 96的表达进行了评估，流式细胞术在急性失代偿期肝硬化（AD）和ACLF患者，与健康对照组（HC）（n = 8每组）。另一队列中，用Luminex多重分析法测定了AD（n = 8）和ACLF（n = 23）患者血浆可溶性CD 96和CD 155的浓度，并与HC（n = 8）患者进行了比较ACLF中sCD 96浓度高于HC（1541 vs 563.6 pg/ml，p = 0.01，图1B）。sCD 96浓度与Child Pugh评分正相关（r = 0.43，p = 0.02），并且在1个月时ACLF非存活者中高于存活者（2245对1100 pg/ml，p = 0.01，图1C）。与HC相比，ACLF中sCD 155浓度也增加（8875 vs 2686 pg/ml，p = 0.01）。结论ACLF患者中CD 4 + T细胞上抑制性免疫检查点CD 96的表达增加，这反映了较高的血浆sCD 96浓度。后者与肝硬化疾病的严重程度相关，并且在ACLF非幸存者中更高。因此，CD 96可能是ACLF的免疫调节靶点，sCD 96是有用的预后标志物。
BackgroundAcute-on-chronic liver failure (ACLF) is a syndrome characterised by multiple organ failure and high short-term mortality. The condition represents an immunological paradox in that rampant systemic inflammation, which drives organ dysfunction, exists alongside immune cell dysfunction and increased susceptibility to bacterial infections. Understanding the mechanisms that control this balance is therefore critical.CD96 is an immune checkpoint expressed on T cells and NK cells that transmits an inhibitory signal when bound to its ligand CD155 (PVR). Both CD96 and CD155 have soluble forms, with elevated concentrations found in other immunosuppressive states such as cancer and chronic viral infections. In this study we explored the CD96-CD155 immune checkpoint axis in patients with ACLF.MethodThe expression of membrane bound CD96 on peripheral lymphoid cells was assessed by flow cytometry in patients with acute decompensated cirrhosis (AD) and ACLF, compared to healthy controls (HC) (n = 8 per group). In a separate cohort, concentrations of plasma soluble CD96 and CD155 in patients with AD (n = 8) or ACLF (n = 23), compared to HC (n = 8), was determined with a Luminex multiplex assay.ResultsCD4+ T cells from patients with ACLF had increased expression of CD96 than those from HC (46.69 versus 14.04%, p = 0.02, figure 1A) and sCD96 concentrations were higher in ACLF than HC (1541 versus 563.6pg/ml, p = 0.01, figure 1B). sCD96 concentration correlated positively with Child Pugh Score (r = 0.43, p = 0.02) and was higher in ACLF non-survivors at 1 month than survivors (2245 versus 1100 pg/ml, p = 0.01, figure 1C). sCD155 concentrations were also increased in ACLF compared to HC (8875 versus 2686pg/ml, p = 0.01).ConclusionExpression of the inhibitory immune checkpoint CD96 is increased on CD4+ T cells in ACLF patients and this is mirrored by higher plasma sCD96 concentrations. The latter correlates with cirrhosis disease severity and is higher in ACLF non-survivors. CD96 could therefore be an immunomodulatory target in ACLF, and sCD96 a useful prognostic marker.