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Serum Cytokine Alterations Associated with Age of Patients with Nephropathia Epidemica

Shakirova, Venera; Khaertynova, Ilseyar; Markelova, Maria; Tarlinton, Rachael; Behnke, Jerzy; Martynova, Ekaterina; Garanina, Ekaterina; Rizvanov, Albert; Khaiboullina, Svetlana

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Venera Shakirova

Ilseyar Khaertynova

Maria Markelova

Jerzy Behnke

Ekaterina Martynova

Ekaterina Garanina

Albert Rizvanov

Svetlana Khaiboullina


Nephropathia epidemica (NE) is a zoonotic disease caused by hantaviruses transmitted from rodents, endemic in the Republic of Tatarstan, Russia. The disease presents clinically with mild, moderate, and severe forms, and time-dependent febrile, oliguric, and polyuric stages of the disease are also recognized. The patient's cytokine responses have been suggested to play a central role in disease pathogenesis; however, little is known about the different patterns of cytokine expression in NE in cohorts of different ages and sexes. Serum samples and clinical records were collected from 139 patients and 57 controls (healthy donors) and were used to analyze 48 analytes with the Bio-Plex multiplex magnetic bead-based antibody detection kits. Principal component analysis of 137 patient and 55 controls (for which there was full data) identified two components that individually accounted for >15% of the total variance in results and together for 38% of the total variance. PC1 represented a proinflammatory TH17/TH2 cell antiviral cytokine profile and PC2 a more antiviral cytokine profile with patients tending to display one or the other of these. Severity of disease and stage of illness did not show any correlation with PC1 profiles; however, significant differences were seen in patients with high PC1 profiles vs. lower for a number of individual clinical parameters: High PC1 patients showed a reduced number of febrile days, but higher maximum urine output, higher creatinine levels, and lower platelet levels. Overall, the results of this study point towards a stronger proinflammatory profile occurring in younger NE patients, this being associated with markers of acute kidney injury and low levels of high-density cholesterol. This is consistent with previous work indicating that the pathology of NE is immune driven, with an inflammatory immune response being associated with disease and that this immune response is more extreme in younger patients.


Shakirova, V., Khaertynova, I., Markelova, M., Tarlinton, R., Behnke, J., Martynova, E., …Khaiboullina, S. (2022). Serum Cytokine Alterations Associated with Age of Patients with Nephropathia Epidemica. BioMed Research International, 2022, Article 4685288.

Journal Article Type Article
Acceptance Date Dec 17, 2021
Online Publication Date Jan 11, 2022
Publication Date Jan 11, 2022
Deposit Date Dec 23, 2021
Publicly Available Date Dec 23, 2021
Journal BioMed Research International
Print ISSN 2314-6133
Electronic ISSN 2314-6141
Publisher Hindawi Publishing Corporation
Peer Reviewed Peer Reviewed
Volume 2022
Article Number 4685288
Keywords General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine
Public URL
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