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Biomarkers for the diagnosis of infectious and inflammatory diseases
Y. A. Menchits,
M. A. Gordukova,
I. V. Obraztsov,
A. V. Eremeeva,
I. A. Korsunsky,
L. A. Fedorova,
D. A. Kudlai,
A. A. Korsunsky https://doi.org/10.21508/1027-4065-2025-70-1-18-25
Abstract
This review focuses on the analysis of biomarkers for the diagnosis and prognosis of infections in immunocompromised children, with particular emphasis on their role in early diagnosis and risk assessment. The study is based on scientific publications from the PubMed database, including analyses of immunological markers, genetic predispositions, and biomarker measurement methods. The key findings highlight the importance of biomarkers such as procalcitonin and presepsin for early diagnosis, IL-6 for predicting disease progression, and TREC and KREC for monitoring neonatal immune status. Promising areas of study include genetic markers and the evaluation of neutrophil extracellular traps to predict sepsis outcomes. The practical application of these biomarkers can improve the diagnosis and monitoring of infections in immunocompromised children, reducing mortality and complications while enhancing treatment efficacy. The study’s conclusions underscore the importance of integrating biomarkers into personalized approaches to diagnosing and predicting infectious diseases in children with immune system impairments.
About the Authors
Y. A. Menchits
First Moscow State Medical University named after I.M. Sechenov (Sechenov University);
Russian Federation
Russian Federation
Moscow
M. A. Gordukova
Speransky Children’s Hospital No. 9, Moscow Health Department
Russian Federation
Russian Federation
Moscow
I. V. Obraztsov
Speransky Children’s Hospital No. 9, Moscow Health Department
Russian Federation
Russian Federation
Moscow
A. V. Eremeeva
First Moscow State Medical University named after I.M. Sechenov (Sechenov University)
Russian Federation
Russian Federation
Moscow
I. A. Korsunsky
First Moscow State Medical University named after I.M. Sechenov (Sechenov University)
Russian Federation
Russian Federation
Moscow
L. A. Fedorova
First Moscow State Medical University named after I.M. Sechenov (Sechenov University); Speransky Children’s Hospital No. 9, Moscow Health Department
Russian Federation
Russian Federation
Moscow
D. A. Kudlai
First Moscow State Medical University named after I.M. Sechenov (Sechenov University); National Research Center — Institute of Immunology Federal Medical-Biological Agency of Russia; JSC «GENERIUM»
Russian Federation
Russian Federation
Moscow
A. A. Korsunsky
First Moscow State Medical University named after I.M. Sechenov (Sechenov University); Speransky Children’s Hospital No. 9, Moscow Health Department
Russian Federation
Russian Federation
Moscow
References
1. Naghavi M., Abajobir A.A., Abbafati C., Abbas K.M., Abd-Allah F., Abera S.F., et al. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet 2017; 390: 1151–210. DOI: 10.1016/S0140–6736(17)32152–9
2. Nelson R.E., Hatfield K.M., Wolford H., Samore M.H., Scott R.D., Reddy S.C., et al. National Estimates of Healthcare Costs Associated With Multidrug-Resistant Bacterial Infections Among Hospitalized Patients in the United States. Clin Infect Dis 2021; 72: S17–26. DOI: org/10.1093/CID/CIAA1581
3. Mejias A., Wu B., Tandon N., Chow W., Varma R., Franco E., et al. Risk of childhood wheeze and asthma after respiratory syncytial virus infection in full-term infants. Pediatr Allergy Immunol 2020; 31: 47–56. DOI: 10.1111/pai.13131
4. Ouellette C.P., Sánchez P.J., Xu Z., Blankenship D., Zeray F., Ronchi A., et al. Blood genome expression profiles in infants with congenital cytomegalovirus infection. Nat Commun 2020; 11. DOI: 10.1038/S41467–020–17178–5
5. Godfred-Cato S., Bryant B., Leung J., Oster M.E., Conklin L., Abrams J., et al. COVID-19-Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020. Morbidity and Mortality Weekly Report 2020; 69: 1074. DOI: 10.15585/MMWR.MM6932E2
6. Bousfiha A., Moundir A., Tangye S.G., Picard C., Jeddane L., Al-Herz W., et al. The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity. J Clin Immunol 2022;42:1508–1520. DOI: org/10.1007/s10875–022–01352-z/metrics
7. Redmond M.T., Scherzer R., Prince B.T. Novel Genetic Discoveries in Primary Immunodeficiency Disorders. Clin Rev Allergy Immunol 2022; 63: 55. DOI: 10.1007/S12016–021–08881–2
8. Godfrey A., Vandendriessche B., Bakker J.P., Fitzer-Attas C., Gujar N., Hobbs M., et al. Fit-for-Purpose Biometric Monitoring Technologies: Leveraging the Laboratory Biomarker Experience. Clin Transl Sci 2021; 14: 62. DOI: 10.1111/cts.12865
9. Mayeux R. Biomarkers: Potential Uses and Limitations. NeuroRx. 2004; 1: 182. DOI: 10.1602/neurorx.1.2.182
10. Wan-Ibrahim W.I., Singh V.A., Hashim O.H., Abdul-Rahman P.S. Biomarkers for Bone Tumors: Discovery from Genomics and Proteomics Studies and Their Challenges. Mol Med 2015; 21: 861. DOI: org/10.2119/MOLMED.2015.00183
11. Mert D.G., Terzi H. Mean platelet volume in bipolar disorder: the search for an ideal biomarker. Neuropsychiatr Dis Treat 2016; 12: 2057. DOI: org/10.2147/NDT.S112374
12. Van Der Poll T., Van De Veerdonk F.L., Scicluna B.P., Netea M.G. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol 2017; 17: 407–420. DOI: 10.1038/NRI.2017.36
13. Langlais D., Fodil N., Gros P. Genetics of Infectious and Inflammatory Diseases: Overlapping Discoveries from Association and Exome-Sequencing Studies. Annu Rev Immunol 2017; 35: 1–30. DOI: 10.1146/annurev-immunol-051116–052442
14. Zhong Y., Xu F., Wu J., Schubert J., Li M.M. Application of Next Generation Sequencing in Laboratory Medicine. Ann Lab Med 2021; 41: 25–43. DOI: 10.3343/alm.2021.41.1.25
15. Asgari S., McLaren P.J., Peake J., Wong M., Wong R., Bartha I., et al. Exome Sequencing Reveals Primary Immunodeficiencies in Children with Community-Acquired Pseudomonas aeruginosa Sepsis. Front Immunol 2016; 7. DOI: 10.3389/fimmu.2016.00357
16. Borghesi A., Trück J., Asgari S., Sancho-Shimizu V., Agyeman P.K.A., Bellos E., et al. Whole-exome Sequencing for the Identification of Rare Variants in Primary Immunodeficiency Genes in Children With Sepsis: A Prospective, Population-based Cohort Study. Clin Infect Dis 2020; 71: E614–23. DOI: 10.1093/cid/ciaa290
17. Hermans P.W.M., Hibberd M.L., Booy R., Daramola O., Hazelzet J.A., De Groot R., et al. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Lancet 1999; 354: 556–560. DOI: 10.1016/S0140–6736(99)02220–5
18. Brouwer M.C., Read R.C., van de Beek D. Host genetics and outcome in meningococcal disease: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10: 262–274. DOI: 10.1016/S1473–3099(10)70045–1
19. Mazzotti L., Gaimari A., Bravaccini S., Maltoni R., Cerchione C., Juan M., et al. T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer. Int J Mol Sci 2022; 23. DOI: 10.3390/IJMS23158590/S1
20. Korsunskiy I., Blyuss O., Gordukova M., Davydova N., Zaikin A., Zinovieva N., et al. Expanding TREC and KREC Utility in Primary Immunodeficiency Diseases Diagnosis. Front Immunol 2020; 11: 320. DOI: 10.3389/FIMMU.2020.00320
21. Sottini A., Serana F., Bertoli D., Chiarini M., Valotti M., Tessitore M.V., et al. Simultaneous Quantification of T-Cell Receptor Excision Circles (TRECs) and K-Deleting Recombination Excision Circles (KRECs) by Real-time PCR. J Vis Exp 2014; 94: 52184. DOI: 10.3791/52184
22. Borte S., Von Döbeln U., Fasth A., Wang N., Janzi M., Winiarski J., et al. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood 2012; 119: 2552–2555. DOI: 10.1182/blood-2011–08–371021
23. Korsunskiy I., Blyuss O., Gordukova M., Davydova N., Gordleeva S., Molchanov R., et al. TREC and KREC levels as predictors of lymphocyte subpopulations measured by flow cytometry. Front Physiol 2019; 10. DOI: 10.3389/fphys.2018.01877
24. Remaschi G., Ricci S., Cortimiglia M., De Vitis E., Iannuzzi L., Boni L., et al. TREC and KREC in very preterm infants: reference values and effects of maternal and neonatal factors. J Maternal-Fetal Neonatal Med 2021; 34: 3946–3951. DOI: 10.1080/14767058.2019.1702951
25. Zanotti C., Chiarini M., Serana F., Sottini A., Garrafa E., Torri F., et al. Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients. Clin Immunol 2012; 145: 19–26. DOI: 10.1016/J.CLIM.2012.07.007
26. Sottini A., Capra R., Zanotti C., Chiarini M., Serana F., Ricotta D., et al. Pre-existing T- and B-cell defects in one progressive multifocal leukoencephalopathy patient. PLoS One 2012; 7. DOI: 10.1371/journal.pone.0034493
27. Masuda S., Nakazawa D., Shida H., Miyoshi A., Kusunoki Y., Tomaru U., et al. NETosis markers: Quest for specific, objective, and quantitative markers. Clinica Chimica Acta 2016; 459: 89–93. DOI: 10.1016/J.CCA.2016.05.029
28. Xu J., Zhang X., Pelayo R., Monestier M., Ammollo C. T., Semeraro F., et al. Extracellular histones are major mediators of death in sepsis. Nat Med 2009; 15: 1318–21. DOI: 10.1038/NM.2053
29. Fuchs T.A., Brill A., Wagner D.D. Neutrophil extracellular trap (NET) impact on deep vein thrombosis. Arterioscler Thromb Vasc Biol 2012; 32: 1777–1783. DOI: 10.1161/atvbaha.111.242859
30. Nakazawa D., Tomaru U., Suzuki A., Masuda S., Hasegawa R., Kobayashi T., et al. Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: Implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2012; 64: 3779–3787. DOI: 10.1002/art.34619
31. Zhang H., Wang Y., Qu M., Li W., Wu D., Cata J. P., et al. Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis. Clin Transl Med 2023; 13. DOI: 10.1002/ctm2.1170
32. Zhang Y.Y., Ning B.T. Signaling pathways and intervention therapies in sepsis. Signal Transduct Target Ther 2021; 6. DOI: 10.1038/S41392–021–00816–9
33. Ackermann M., Anders H. J., Bilyy R., Bowlin G. L., Daniel C., De Lorenzo R., et al. Patients with COVID-19: in the dark- NETs of neutrophils. Cell Death Differ 2021; 28: 3125–3139. DOI: 10.1038/S41418–021–00805-Z
34. Russell C.D., Baillie J.K. Treatable traits and therapeutic targets: Goals for systems biology in infectious disease. Curr Opin Syst Biol 2017; 2: 140–146. DOI: 10.1016/j.coisb.2017.04.003
35. Ghezzi P., Cerami A. Tumor necrosis factor as a pharmacological target. Methods Mol Med 2004; 98: 1–8. DOI: 10.1385/1–59259–771–8:001
36. Qiu P., Cui X., Barochia A., Li Y., Natanson C., Eichacker P.Q. The evolving experience with therapeutic TNF inhibition in sepsis: considering the potential influence of risk of death. Expert Opin Investig Drugs 2011; 20: 1555–64. DOI: 10.1517/13543784.2011.623125
37. Cannon J.G., Tompkins R.G., Gelfand J.A., Michie H.R., Stanford G.G., van der Meer J.W.M., et al. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis 1990; 161: 79–84. DOI: 10.1093/infdis/161.1.79
38. Joosten L.A.B., Van De Veerdonk F.L., Vonk A.G., Boerman O.C., Keuter M., Fantuzzi G., et al. Differential susceptibility to lethal endotoxaemia in mice deficient in IL-1α, IL-1β or IL-1 receptor type I. APMIS 2010; 118: 1000–1007. DOI: 10.1111/J.1600–0463.2010.02684.X
39. Obraztsov I.V., Chernikova E.A., Obraztsova A.A., Epifanova M.A., Zhirkova Yu.V. Interleukin-6 as a marker of infection generalization in neonatal sepsis. Anesteziologija i reanimatologija 2024; 3: 35–42. (in Russ.) DOI: 10.17116/anaesthesiology202403135
40. Kao P.C., Shiesh S.C., Wu T.J. Serum C-reactive protein as a marker for wellness assessment. Ann Clin Lab Sci 2006 Spring; 36(2): 163–169.
41. Whelan S.A., Hendricks N., Dwight Z.L., Fu Q., Moradian A., Van Eyk J.E. et al. Assessment of a 60-Biomarker Health Surveillance Panel (HSP) on Whole Blood from Remote Sampling Devices by Targeted LC/MRM-MS and Discovery DIA-MS Analysis. Anal Chem 2023; 95(29): 11007–11018. DOI: 10.1021/acs.analchem.3c01189
42. Mauri T., Bellani G., Patroniti N., Coppadoro A., Peri G., Cuccovillo I., et al. Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality. Intensive Care Med 2010; 36: 621–629. DOI: 10.1007/S00134–010–1752–5
43. Kofoed K., Andersen O., Kronborg G., Tvede M., Petersen J., Eugen-Olsen J., et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care 2007; 11: R38. DOI: 10.1186/cc5723
44. Shapiro N.I., Trzeciak S., Hollander J.E., Birkhahn R., Otero R., Osborn T.M., et al. A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis. Crit Care Med 2009; 37: 96–104. DOI: 10.1097/ccm.0b013e318192fd9d
45. Gibot S., Béné M.C., Noel R., Massin F., Guy J., Cravoisy A., et al. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med 2012; 186: 65–71. DOI: 10.1164/rccm.201201–0037oc
46. Stryjewski G.R., Nylen E.S., Bell M.J., Snider R.H., Becker K.L., Wu A., et al. Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children. Pediatr Crit Care Med 2005; 6: 129–135. DOI: 10.1097/01.pcc.0000149317.15274.48
47. Bozza F.A., Salluh J.I., Japiassu A.M., Soares M., Assis E.F., Gomes R.N., et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 2007; 11. DOI: 10.1186/cc5783
48. Monneret G., Finck M. E., Venet F., Debard A. L., Bohé J., Bienvenu J., et al. The anti-inflammatory response dominates after septic shock: association of low monocyte HLA-DR expression and high interleukin-10 concentration. Immunol Lett 2004; 95: 193–198. DOI: 10.1016/j.imlet.2004.07.009
49. Guignant C., Lepape A., Huang X., Kherouf H., Denis L., Poitevin F., et al. Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Crit Care 2011; 15. DOI: 10.1186/cc10112
50. Urbonas V., Eidukaitė A., Tamulienė I. Increased interleukin-10 levels correlate with bacteremia and sepsis in febrile neutropenia pediatric oncology patients. Cytokine 2012; 57: 313–315. DOI: 10.1016/j.cyto.2011.11.012
51. Zeitoun A.A.H., Gad S.S., Attia F.M., Abu Maziad A.S., Bell E.F. Evaluation of neutrophilic CD64, interleukin 10 and procalcitonin as diagnostic markers of early- and late-onset neonatal sepsis. Scand J Infect Dis 2010; 42: 299–305. DOI: 10.3109/00365540903449832
52. Shubin N.J., Navalkar K., Sampson D., Yager T.D., Cermelli S., Seldon T., et al. Serum Protein Changes in Pediatric Sepsis Patients Identified With an Aptamer-Based Multiplexed Proteomic Approach. Crit Care Med 2020; 48: E48–57. DOI: 10.1097/ccm.0000000000004083
53. Pilar-Orive F.J., Astigarraga I., Azkargorta M., Elortza F., Garcia-Obregon S. A Three-Protein Panel to Support the Diagnosis of Sepsis in Children. J Clin Med 2022; 11. DOI: 10.3390/jcm11061563
54. Luo T., Yan H., Li X., Deng Y., Huang J., Li L., et al. Proteomic analysis identified potential age-associated prognostic biomarkers in pneumonia-derived paediatric sepsis. Proteomics Clin Appl 2022; 16. DOI: 10.1002/prca.202100036
55. Wong H.R., Cvijanovich N.Z., Hall M., Allen G.L., Thomas N.J., Freishtat R.J., et al. Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children. Crit Care 2012; 16. DOI: 10.1186/CC11847
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For citations:
Menchits Y.A., Gordukova M.A., Obraztsov I.V., Eremeeva A.V., Korsunsky I.A., Fedorova L.A., Kudlai D.A., Korsunsky A.A. Biomarkers for the diagnosis of infectious and inflammatory diseases. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2025;70(1):18-25. (In Russ.) https://doi.org/10.21508/1027-4065-2025-70-1-18-25
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