Serum Concentrations of TIM-3, LAG-3, and PD-1 in Patients with Hemorrhagic Fever with Renal Syndrome

Author:

Mačak Šafranko Željka1,Jakopec Lana1,Svaguša Karla1,Cvetko Krajinović Lidija1ORCID,Tomasović Domagoj1,Lukić Ljiljana1ORCID,Markotić Alemka123

Affiliation:

1. Research Unit, University Hospital for Infectious Diseases “Dr. Fran Mihaljevic”, 10000 Zagreb, Croatia

2. Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia

3. Faculty of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia

Abstract

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease widespread in Europe and Asia. HFRS is caused by negative-sensed single-stranded RNA orthohantaviruses transmitted to humans through inhaling aerosolized excreta of infected rodents. Symptoms of HFRS include acute kidney injury, thrombocytopenia, hemorrhages, and hypotension. The immune response raised against viral antigens plays an important role in the pathogenesis of HFRS. Inhibitory co-receptors are essential in regulating immune responses, mitigating immunopathogenesis, and reducing tissue damage. Our research showed an increased soluble form of inhibitory co-receptors TIM-3, LAG-3, and PD-1 in HFRS patients associated with disease severity. Our study aimed to investigate the impact of HFRS on the concentrations of soluble forms of inhibitory receptors TIM-3, LAG-3, and PD-1 in the patient’s serum and the potential correlation with key clinical parameters. Our study aimed to investigate the impact of HFRS on the concentrations of soluble forms of inhibitory receptors TIM-3, LAG-3, and PD-1 in the patient’s serum and their possible association with relevant clinical parameters. Using multiplex immunoassay, we found elevated levels of TIM-3, LAG-3, and PD-1 proteins in the serum of HFRS patients. Furthermore, increased levels were associated with creatinine, urea, lactate dehydrogenase concentrations, and platelet count. These findings suggest that these proteins play a role in regulating the immune response and disease progression.

Funder

Strengthening the capacity of CerVirVac for. research in virus immunology and vaccinology

European Regional Development Fund

Publisher

MDPI AG

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