John van Geest Centre for Brain Repair, Department of Clinical Neuroscience, University of Cambridge, Cambridge, U.K.
CamKolInv, Cambridge Kolkata Innovation and Therapeutic Limited, Cambridge, U.K.
Biosci Rep. 2020 Dec 23;40(12). doi: 10.1042/BSR20203092.
In some individuals, coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leads to a variety of serious inflammatory symptoms, including blood clotting and acute respiratory distress. Death due to COVID-19 shows a steep rise in relation to age. Comorbidities such as type 2 diabetes mellitus (T2DM), hypertension, and cardiovascular disease also increase susceptibility. It has been reported that T-cell regulatory dipeptidyl peptidase 4 (DPP4; cluster of differentiation 26 (CD26)) binds to the external spike (S) glycoprotein of SARS-CoV-2 as a receptor, for the viral entry into the host cell. CD26 is expressed on many cells, including T and natural killer (NK) cells of the immune system, as a membrane-anchored form. A soluble form (sCD26) is also found in the blood plasma and cerebrospinal fluid (CSF). Approach and results: To investigate a possible relationship between sCD26 levels, age and pathology, serum samples were collected from control, T2DM and age-related dementia (ARD) subjects. A significant reduction in serum sCD26 levels was seen in relation to age. ARD and T2DM were also associated with lower levels of sCD26. The analysis of blood smears revealed different cellular morphologies: in controls, CD26 was expressed around the neutrophil membrane, whereas in T2DM, excessive sCD26 was found around the mononucleated cells (MNCs). ARD subjects had abnormal fragmented platelets and haemolysis due to low levels of sCD26.
These findings may help to explain the heterogeneity of SARS-CoV-2 infection. High serum sCD26 levels could protect from viral infection by competively inhibiting the virus binding to cellular CD26, whereas low sCD26 levels could increase the risk of infection. If so measuring serum sCD26 level may help to identify individuals at high risk for the COVID-19 infection.
在某些个体中，冠状病毒严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染导致多种严重炎症症状，包括血栓形成和急性呼吸窘迫。COVID-19 导致的死亡与年龄呈陡峭上升趋势。2 型糖尿病（T2DM）、高血压和心血管疾病等合并症也会增加易感性。据报道，T 细胞调节二肽基肽酶 4（DPP4；分化群 26（CD26））作为受体与 SARS-CoV-2 的外部刺突（S）糖蛋白结合，从而使病毒进入宿主细胞。CD26 在许多细胞上表达，包括免疫系统的 T 细胞和自然杀伤（NK）细胞，作为膜锚定形式。也可以在血浆和脑脊液（CSF）中发现可溶性形式（sCD26）。方法和结果：为了研究 sCD26 水平、年龄和病理学之间的可能关系，从对照、T2DM 和年龄相关性痴呆（ARD）患者中采集血清样本。血清 sCD26 水平与年龄呈显著降低趋势。ARD 和 T2DM 也与 sCD26 水平降低相关。血液涂片分析显示不同的细胞形态：在对照中，CD26 表达在中性粒细胞膜周围，而在 T2DM 中，过多的 sCD26 发现于单核细胞（MNCs）周围。ARD 患者由于 sCD26 水平低而出现异常的血小板碎片和溶血。结论：这些发现可能有助于解释 SARS-CoV-2 感染的异质性。高血清 sCD26 水平可能通过竞争性抑制病毒与细胞 CD26 的结合来保护免受病毒感染，而低 sCD26 水平可能增加感染风险。如果是这样，测量血清 sCD26 水平可能有助于识别 COVID-19 感染高危个体。
