Investigation of CD26, a potential SARS-CoV-2 receptor, as a biomarker of age and pathology

Author:

Raha Animesh Alexander12,Chakraborty Subhojit12,Henderson James1,Mukaetova-Ladinska Elizabeta3,Zaman Shahid4,Trowsdale John5,Raha-Chowdhury Ruma124ORCID

Affiliation:

1. John van Geest Centre for Brain Repair, Department of Clinical Neuroscience, University of Cambridge, Cambridge, U.K.

2. CamKolInv, Cambridge Kolkata Innovation and Therapeutic Limited, Cambridge, U.K.

3. Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, U.K.

4. Department of Psychiatry, Cambridge Intellectual and Developmental Disabilities Research Group, Cambridge, U.K.

5. Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, U.K.

Abstract

Abstract Objective: 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. Conclusions: 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.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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