Central Institute for Medical and Chemical Laboratory Diagnosis, Tirol Kliniken GmbH, Innsbruck, Austria.
Department of Internal Medicine II, Innsbruck Medical University, Innsbruck, Austria.
Clin Chem Lab Med. 2023 Jul 3;61(12):2248-2255. doi: 10.1515/cclm-2023-0232. Print 2023 Nov 27.
Immune checkpoints play an important role in maintaining the balance of the immune system and in the development of autoimmune diseases. A central checkpoint molecule is the programmed cell death protein 1 (PD-1, CD279) which is typically located on the surface of T cells. Its primary ligand PD-L1 is expressed on antigen presenting cells and on cancer cells. Several variants of PD-L1 exist, among these soluble molecules (sPD-L1) present in serum at low concentrations. sPD-L1 was found elevated in cancer and several other diseases. sPD-L1 in infectious diseases has received relatively little attention so far and is therefore subject of this study.
sPD-L1 serum levels were determined in 170 patients with viral infections (influenza, varicella, measles, Dengue fever, SARS-CoV2) or bacterial sepsis by ELISA and compared to the levels obtained in 11 healthy controls.
Patients with viral infections and bacterial sepsis generally show significantly higher sPD-L1 serum levels compared to healthy donors, except for varicella samples where results do not reach significance. sPD-L1 is increased in patients with impaired renal function compared to those with normal renal function, and sPD-L1 correlates significantly with serum creatinine. Among sepsis patients with normal renal function, sPD-L1 serum levels are significantly higher in Gram-negative sepsis compared to Gram-positive sepsis. In addition, in sepsis patients with impaired renal function, sPD-L1 correlates positively with ferritin and negatively with transferrin.
sPD-L1 serum levels are significantly elevated in patients with sepsis, influenza, mesasles, Dengue fever or SARS-CoV2. Highest levels are detectable in patients with measles and Dengue fever. Also impaired renal function causes an increase in levels of sPD-L1. As a consequence, renal function has to be taken into account in the interpretation of sPD-L1 levels in patients.
免疫检查点在维持免疫系统平衡和自身免疫性疾病的发展中起着重要作用。一个核心的检查点分子是程序性细胞死亡蛋白 1（PD-1，CD279），它通常位于 T 细胞表面。其主要配体 PD-L1 表达在抗原呈递细胞和癌细胞上。PD-L1 存在几种变体，其中包括在血清中低浓度存在的可溶性分子（sPD-L1）。sPD-L1 在癌症和其他几种疾病中升高。到目前为止，传染病中的 sPD-L1 受到的关注相对较少，因此是本研究的主题。
通过 ELISA 法测定 170 例病毒感染（流感、水痘、麻疹、登革热、SARS-CoV2）或细菌性败血症患者的 sPD-L1 血清水平，并与 11 例健康对照者的水平进行比较。
与健康供体相比，病毒感染和细菌性败血症患者的 sPD-L1 血清水平通常显著升高，除了水痘样本结果无显著差异。与肾功能正常的患者相比，肾功能受损的患者 sPD-L1 增加，sPD-L1 与血清肌酐显著相关。在肾功能正常的败血症患者中，革兰氏阴性败血症患者的 sPD-L1 血清水平明显高于革兰氏阳性败血症患者。此外，在肾功能受损的败血症患者中，sPD-L1 与铁蛋白呈正相关，与转铁蛋白呈负相关。
败血症、流感、麻疹、登革热或 SARS-CoV2 患者的 sPD-L1 血清水平显著升高。麻疹和登革热患者可检测到最高水平。此外，肾功能受损也会导致 sPD-L1 水平升高。因此，在解释患者的 sPD-L1 水平时，必须考虑肾功能。
