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Mester P, Keller D, Kunst C, Schmid S, Krautbauer S, Müller M, Buechler C, Pavel V. Elevated Serum Presepsin Identifies Herpes Simplex Virus-1 Reactivation in COVID-19 Patients. Viruses 2025; 17:357. [PMID: 40143286 PMCID: PMC11946436 DOI: 10.3390/v17030357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 02/26/2025] [Accepted: 02/27/2025] [Indexed: 03/28/2025] Open
Abstract
Presepsin, a cleaved peptide of soluble CD14, may become a promising biomarker for assessing disease severity and mortality in coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 frequently develop bacterial and fungal superinfections, as well as herpes simplex virus-1 (HSV-1) reactivation, which may exacerbate disease progression. This study aimed to evaluate the impact of concomitant infections on serum presepsin levels. Serum presepsin levels were measured using an enzyme-linked immunosorbent assay (ELISA) in 63 patients with moderate COVID-19, 60 patients with severe disease, and 49 healthy controls. Correlations with procalcitonin and the presence of superinfections or HSV-1 reactivation were assessed. Consistent with previous studies, serum presepsin levels were the highest in patients with severe COVID-19 (p = 0.002 compared to patients with moderate disease). Within this group, non-survivors exhibited significantly elevated presepsin levels (p = 0.027). A positive correlation between presepsin and procalcitonin was observed in both moderate and severe COVID-19 cases. Patients with bacterial or fungal superinfections showed presepsin levels comparable to those without secondary infections. However, presepsin levels were markedly elevated in patients with HSV-1 reactivation (p = 0.002). After excluding patients with HSV-1 reactivation, presepsin levels no longer differed between moderate and severe COVID-19 cases, though they remained higher than in healthy controls (p < 0.001 for both comparisons). In conclusion, these findings suggest that elevated serum presepsin levels in severe COVID-19 are primarily driven by HSV-1 reactivation rather than bacterial or fungal superinfections.
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Affiliation(s)
- Patricia Mester
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, Immunology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (P.M.); (D.K.); (C.K.); (S.S.); (M.M.); (V.P.)
| | - Dennis Keller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, Immunology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (P.M.); (D.K.); (C.K.); (S.S.); (M.M.); (V.P.)
| | - Claudia Kunst
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, Immunology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (P.M.); (D.K.); (C.K.); (S.S.); (M.M.); (V.P.)
| | - Stephan Schmid
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, Immunology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (P.M.); (D.K.); (C.K.); (S.S.); (M.M.); (V.P.)
| | - Sabrina Krautbauer
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany;
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, Immunology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (P.M.); (D.K.); (C.K.); (S.S.); (M.M.); (V.P.)
| | - Christa Buechler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, Immunology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (P.M.); (D.K.); (C.K.); (S.S.); (M.M.); (V.P.)
| | - Vlad Pavel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, Immunology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (P.M.); (D.K.); (C.K.); (S.S.); (M.M.); (V.P.)
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Kouroupis D, Zografou I, Balaska A, Reklou A, Varouktsi A, Paschala A, Pyrpasopoulou A, Stavropoulos K, Vogiatzis K, Sarvani A, Doukelis P, Karangelis D, Dimakopoulos G, Kotsa K, Doumas M, Koufakis T. Presepsin Levels in Infection-Free Subjects with Diabetes Mellitus: An Exploratory Study. Biomedicines 2024; 12:1960. [PMID: 39335474 PMCID: PMC11428571 DOI: 10.3390/biomedicines12091960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 08/21/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024] Open
Abstract
Systemic inflammation has been recognized as the cause and consequence of metabolic dysregulation in diabetes mellitus (DM). Presepsin has recently emerged as a promising biomarker for the detection of bacterial infections and sepsis. There is evidence that gut dysbiosis results in the increased circulating concentrations of Gram-negative bacteria lipopolysaccharide, the linkage of presepsin, which in turn promotes insulin resistance and correlates with the risk of diabetic complications. Thus, we hypothesized that presepsin could reflect the magnitude of systemic inflammation and metabolic decompensation in patients with DM even in the absence of infection. In this cross-sectional pilot study, we included 75 infection-free individuals with well-controlled (n = 19) and uncontrolled (n = 23) type 2 diabetes (T2D), well-controlled (n = 10) and uncontrolled (n = 10) type 1 diabetes (T1D), and normoglycemic controls (n = 13). Presepsin levels were compared between the groups and potential associations with demographic, clinical, and laboratory parameters were explored. We observed that the duration of DM was associated with presepsin values (p = 0.008). When the participants were classified into the type of DM groups, the presepsin levels were found to be lower in the patients with T2D compared to those with T1D (p = 0.008). However, significance in that case was driven by the difference between the well-controlled groups. After adjusting for the effects of DM duration, presepsin was significantly lower in the well-controlled T2D group compared to the well-controlled T1D group [1.34 (2.02) vs. 2.22 (4.20) ng/mL, p = 0.01]. Furthermore, we adjusted our findings for various confounders, including age, body mass index, and waist circumference, and found that the difference in the presepsin values between the adequately controlled groups remained significant (p = 0.048). In conclusion, our findings suggest that presepsin could potentially serve as a surrogate marker of inflammation and metabolic control in people with DM.
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Affiliation(s)
- Dimitrios Kouroupis
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Ioanna Zografou
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Aikaterini Balaska
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Andromachi Reklou
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Anna Varouktsi
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Anastasia Paschala
- Department of Internal Medicine, G. Papanikolaou General Hospital, 570 10 Thessaloniki, Greece;
| | - Athina Pyrpasopoulou
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Konstantinos Stavropoulos
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Konstantinos Vogiatzis
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Anastasia Sarvani
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Panagiotis Doukelis
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Dimos Karangelis
- Department of Cardiothoracic Surgery, Democritus University of Thrace, University General Hospital, 681 00 Alexandroupolis, Greece;
| | - Georgios Dimakopoulos
- BIOSTATS, Epirus Science and Technology Park Campus of the University of Ioannina, 451 10 Ioannina, Greece;
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 546 36 Thessaloniki, Greece;
| | - Michael Doumas
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
| | - Theocharis Koufakis
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece; (D.K.); (I.Z.); (A.B.); (A.R.); (A.V.); (A.P.); (K.S.); (K.V.); (A.S.); (P.D.); (M.D.)
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Marin MJ, van Wijk XMR, Chambliss AB. Advances in sepsis biomarkers. Adv Clin Chem 2024; 119:117-166. [PMID: 38514209 DOI: 10.1016/bs.acc.2024.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2024]
Abstract
Sepsis, a dysregulated host immune response to an infectious agent, significantly increases morbidity and mortality for hospitalized patients worldwide. This chapter reviews (1) the basic principles of infectious diseases, pathophysiology and current definition of sepsis, (2) established sepsis biomarkers such lactate, procalcitonin and C-reactive protein, (3) novel, newly regulatory-cleared/approved biomarkers, such as assays that evaluate white blood cell properties and immune response molecules, and (4) emerging biomarkers and biomarker panels to highlight future directions and opportunities in the diagnosis and management of sepsis.
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Affiliation(s)
- Maximo J Marin
- Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, Florida, USA
| | | | - Allison B Chambliss
- Department of Pathology & Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA
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Takahashi G, Hoshikawa K, Suzuki R, Sato K, Hoshi S, Yoshinao D, Shirakawa K. Development of a newly immunoassay specific for mouse presepsin (sCD14-ST). Sci Rep 2022; 12:21724. [PMID: 36522357 PMCID: PMC9755121 DOI: 10.1038/s41598-022-22096-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 10/10/2022] [Indexed: 12/23/2022] Open
Abstract
Presepsin (sCD14-ST) is used as a marker for sepsis diagnosis. The production mechanism of presepsin is unique in that it is produced through phagocytosis of microorganisms. However, some studies have demonstrated that non-infected patients had increased presepsin levels and that presepsin is related to the risk or severity of diseases. This study was designed to describe a sensitive sandwich enzyme-linked immunosorbent assay for mouse presepsin developed to investigate the association of presepsin with diseases. Polyclonal antibodies were generated from peptide-immunized rabbit antiserum. Mouse presepsin standard was prepared using the recombinant method as an Fc-fusion protein. The linear detection range of the method was 4.7-300 pg/mL with a detection limit of 1.4 pg/mL. The assay detected mouse presepsin where mouse soluble CD14 (sCD14) was digested by cathepsin D proteinase and the cross-reactivity of sCD14 was not observed. The normal levels of mouse presepsin and sCD14 were compared; 65.9 ± 21.4 pg/mL and 43.2 ± 7.2 ng/mL were determined, respectively. Moreover, the levels of presepsin and sCD14 were compared with a lipopolysaccharide (LPS)-injected sepsis mouse model. The newly developed analytical method had high specificity to presepsin and is an efficient tool for studying the association between presepsin and diseases.
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Affiliation(s)
- Gaku Takahashi
- grid.411790.a0000 0000 9613 6383Department of Critical Care, Disaster and General Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori Yahaba Town, Iwate, 028-3695 Japan
| | - Kouichi Hoshikawa
- grid.411790.a0000 0000 9613 6383Department of Critical Care, Disaster and General Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori Yahaba Town, Iwate, 028-3695 Japan
| | - Rioto Suzuki
- grid.411790.a0000 0000 9613 6383Department of Critical Care, Disaster and General Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori Yahaba Town, Iwate, 028-3695 Japan
| | - Kotaro Sato
- grid.411790.a0000 0000 9613 6383Department of Critical Care, Disaster and General Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori Yahaba Town, Iwate, 028-3695 Japan
| | - Shintaro Hoshi
- grid.411790.a0000 0000 9613 6383Department of Critical Care, Disaster and General Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori Yahaba Town, Iwate, 028-3695 Japan
| | - Daisuke Yoshinao
- grid.411790.a0000 0000 9613 6383Department of Critical Care, Disaster and General Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori Yahaba Town, Iwate, 028-3695 Japan
| | - Kamon Shirakawa
- Clinical Development Group, LSI Medience Corporation, Tokyo, Japan
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Xiao HL, Wang GX, Wang Y, Tan ZM, Zhou J, Yu H, Xie MR, Li CS. Dynamic blood presepsin levels are associated with severity and outcome of acute pancreatitis: A prospective cohort study. World J Gastroenterol 2022; 28:5203-5216. [PMID: 36188715 PMCID: PMC9516673 DOI: 10.3748/wjg.v28.i35.5203] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/10/2022] [Accepted: 09/01/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute pancreatitis (AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and death. However, scoring systems are complicated and time consuming, and the predictive values for the clinical course are vague.
AIM To determine whether the dynamic changes in presepsin levels can be used to evaluate the severity of disease and outcome of AP.
METHODS In this multicentric cohort study, 133 patients with AP were included. Clinical severity was dynamically evaluated using the 2012 revised Atlanta Classification. Blood presepsin levels were measured at days 1, 3, 5 and 7 after admission by chemiluminescent enzyme immunoassay.
RESULTS The median concentration of presepsin increased and the clearance rate of presepsin decreased with disease severity and organ failure in AP patients. The presepsin levels on days 3, 5 and 7 were independent predictors of moderately severe and severe AP with time-specific area under the curve (AUC) values of 0.827, 0.848 and 0.867, respectively. The presepsin levels positively correlated with bedside index of severity in AP, Ranson, acute physiology and chronic health evaluation II, computed tomography severity index and Marshall scores. Presepsin levels on days 3, 5 and 7 were independent predictors of 28-d mortality of AP patients with AUC values of 0.781, 0.846 and 0.843, respectively.
CONCLUSION Blood presepsin levels within 7 d of admission were associated with and may be useful to dynamically predict the severity of disease course and 28-d mortality in AP patients.
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Affiliation(s)
- Hong-Li Xiao
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Guo-Xing Wang
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Yan Wang
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Zhi-Min Tan
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Jie Zhou
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Han Yu
- Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Miao-Rong Xie
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Chun-Sheng Li
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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Park J, Yoon JH, Ki HK, Ko JH, Moon HW. Performance of presepsin and procalcitonin predicting culture-proven bacterial infection and 28-day mortality: A cross sectional study. Front Med (Lausanne) 2022; 9:954114. [PMID: 36072944 PMCID: PMC9441687 DOI: 10.3389/fmed.2022.954114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 08/02/2022] [Indexed: 11/29/2022] Open
Abstract
Presepsin is a highly specific biomarker for diagnosing bacterial infections, but its clinical usefulness is not well validated. A retrospective cross-sectional study was conducted. Among the patients suspected bacterial infection or fulfilled the criteria of systemic inflammatory response syndrome (SIRS) and patients who underwent blood culture, presepsin, procalcitonin (PCT), and C-reactive protein (CRP) at the same time were included. Receiver operating characteristic (ROC) curve analysis and logistic regression were used to compare performance of three biomarkers. A total of 757 patients were enrolled, including 256 patients (33.8%) with culture-proven bacterial infection and 109 patients (14.4%) with bacteremia. The 28-day mortality rate was 8.6%. ROC curve analysis revealed that the area under the curve (AUC) of PCT was higher than that of presepsin for both culture-proven bacterial infection (0.665 and 0.596, respectively; p = 0.003) and bacteremia (0.791 and 0.685; p < 0.001). In contrast, AUC of PCT for 28-day mortality was slower than presepsin (0.593 and 0.720; p = 0.002). In multivariable logistic regression analysis, PCT showed the highest ORs for culture-proven bacterial infection (OR 2.23, 95% CI 1.55–3.19; p < 0.001) and for bacteremia (OR 5.18, 95% CI 3.13–8.56; p < 0.001), while presepsin showed the highest OR for 28-day mortality (OR 3.31, 95% CI 1.67–6.54; p < 0.001). CRP did not show better performance than PCT or presepsin in any of the analyses. PCT showed the best performance predicting culture-proven bacterial infection and bacteremia, while presepsin would rather be useful as a prognostic marker.
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Affiliation(s)
- Jiho Park
- Division of Infectious Diseases, Department of Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
| | - Ji Hyun Yoon
- Division of Infectious Diseases, Department of Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
| | - Hyun Kyun Ki
- Division of Infectious Diseases, Department of Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
| | - Jae-Hoon Ko
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- *Correspondence: Jae-Hoon Ko,
| | - Hee-Won Moon
- Department of Laboratory Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
- Hee-Won Moon,
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Presepsin production in monocyte/macrophage-mediated phagocytosis of neutrophil extracellular traps. Sci Rep 2022; 12:5978. [PMID: 35396366 PMCID: PMC8993807 DOI: 10.1038/s41598-022-09926-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/30/2022] [Indexed: 12/22/2022] Open
Abstract
Presepsin, a biomarker discovered in Japan, has been clinically applied as a diagnostic aid for sepsis. Recently, however, it has been reported that presepsin levels are elevated in patients with severe systemic lupus erythematosus without infection, suggesting the existence of a production mechanism that does not involve bacterial phagocytosis. In this study, we aimed to elucidate the mechanism of presepsin production without bacterial phagocytosis and explore the clinical significance of presepsin. Neutrophil extracellular traps (NETs) were induced by Escherichia coli and phorbol myristate acetate (PMA) in neutrophils isolated from the peripheral blood of healthy subjects. NET induction alone did not increase presepsin levels, but co-culturing with monocytes significantly increased them. The addition of a NET formation inhibitor also suppressed presepsin levels, suggesting that presepsin production is greatly influenced by monocyte phagocytosis of NETs. Phagocytosis of NETs by THP-1 and U937 cells, which was induced by CD14 expression, also increased presepsin levels. This study suggests that presepsin can be used to assess the severity of inflammatory diseases, such as autoimmune diseases, and monitor treatment effects.
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Antibody-mediated soluble CD14 stabilization prevents agitation-induced increases in presepsin levels in blood component specimens. Biotechniques 2021; 70:160-166. [PMID: 33512240 DOI: 10.2144/btn-2020-0136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Presepsin is a 13-kDa N-terminal glycoprotein of CD14. Previously, agitation-induced increases in presepsin levels have been reported; however, the mechanism remains poorly understood. In this study, we aimed to reveal the mechanism of presepsin increase. The agitated plasma or serum was separated using gel exclusion chromatography and analyzed by ELISA. The effect of an anti-CD14 antibody (F1024-1-3) was examined. We observed elevated presepsin levels in the agitated plasma and aggregated soluble CD14 (sCD14). However, treatment with F1024-1-3 before agitation prevented the aggregation and the increase in presepsin levels. Depletion of aggregated sCD14 decreased the presepsin levels. Our findings indicate that agitation induces the aggregation of sCD14 and triggers an increase in presepsin. Anti-CD14 antibody prevents an increases in presepsin.
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Galliera E, Massaccesi L, de Vecchi E, Banfi G, Romanelli MMC. Clinical application of presepsin as diagnostic biomarker of infection: overview and updates. Clin Chem Lab Med 2020; 58:11-17. [PMID: 31421036 DOI: 10.1515/cclm-2019-0643] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 07/24/2019] [Indexed: 12/23/2022]
Abstract
The appropriate identification of bacterial infection is the basis for effective treatment and control of infective disease. Among this context, an emerging biomarker of infection is presepsin (PSP), recently described as early marker of different infections. PSP secretion has been shown to be associated with monocyte phagocytosis and plasmatic levels of PSP increase in response to bacterial infection and decrease after antibiotic treatment, therefore it can be considered a marker of activation of immune cell response towards an invading pathogen. Different methods have been developed to measure PSP and this review will briefly describe the different clinical fields of application of PSP, ranging from intensive care to neonatal infection, to orthopedic and pulmonary infection as well as fungal infections and cardiovascular infections.
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Affiliation(s)
- Emanuela Galliera
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.,IRCCS Orthopedic Institute Galeazzi, Milan, Italy
| | - Luca Massaccesi
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
| | | | | | - Massimiliano M Corsi Romanelli
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.,U.O.C. SMEL-1 Patologia Clinica IRCCS Policlinico San Donato, San Donato, Milan, Italy
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Handke J, Piazza O, Larmann J, Tesoro S, De Robertis E. Presepsin as a biomarker in perioperative medicine. Minerva Anestesiol 2020; 86:768-776. [DOI: 10.23736/s0375-9393.20.14169-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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11
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Xie QM, Lou QY, Huang SW, Hu HQ, Li SS, Zhang M, Sun XX, Xu JH, Jiang SQ, Liu SX, Xu SQ, Cai J, Liu S, Pan FM, Tao JH, Qian L, Wang CH, Liang CM, Huang HL, Pan HF, Su H, Zou YF. Hsp70 Gene Polymorphisms Are Associated With Disease Susceptibility and HRQOL Improvement in Chinese Han Population With Systemic Lupus Erythematosus. J Clin Rheumatol 2020; 26:134-141. [PMID: 32453286 DOI: 10.1097/rhu.0000000000000986] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.
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Affiliation(s)
- Qiao-Mei Xie
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Qiu-Yue Lou
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Shun-Wei Huang
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | | | - Su-Su Li
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Man Zhang
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Xiu-Xiu Sun
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Jian-Hua Xu
- Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University
| | | | - Sheng-Xiu Liu
- Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital of Anhui Medical University
| | - Sheng-Qian Xu
- Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University
| | - Jing Cai
- Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University
| | - Shuang Liu
- Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University
| | - Fa-Ming Pan
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Jin-Hui Tao
- Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital
| | - Long Qian
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Anhui Medical University
| | - Chun-Huai Wang
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Anhui Medical University
| | - Chun-Mei Liang
- Departments of Laboratory Medicine, School of Public Health
| | - Hai-Liang Huang
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, China
| | - Hai-Feng Pan
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Hong Su
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
| | - Yan-Feng Zou
- From the Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University
- The Key Laboratory of Anhui Medical Autoimmune Diseases
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Presepsin As a Biomarker for Evaluating Prognosis and Early Innate Immune Response of Out-of-Hospital Cardiac Arrest Patients After Return of Spontaneous Circulation. Crit Care Med 2020; 47:e538-e546. [PMID: 30985453 DOI: 10.1097/ccm.0000000000003764] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES After return of spontaneous circulation, patients who experienced out-of-hospital cardiac arrest present an impaired innate immune response that resembles sepsis. Presepsin, a new biomarker for sepsis, has not been studied in out-of-hospital cardiac arrest patients. This study explored the role of presepsin in evaluating the prognosis and early innate immune alteration of out-of-hospital cardiac arrest patients after return of spontaneous circulation by observing presepsin levels, CD14, and human leukocyte antigen-DR expression on monocytes. DESIGN Retrospective analysis. SETTING The emergency department of an urban university tertiary hospital. PARTICIPANTS One hundred sixty-five out-of-hospital cardiac arrest patients with return of spontaneous circulation more than 12 hours, and 100 healthy individuals. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Plasma presepsin and procalcitonin levels were tested after resuscitation (day 0) and on days 1 and 3 after return of spontaneous circulation. Presepsin levels were higher in out-of-hospital cardiac arrest patients than in healthy individuals. In the first 3 days, presepsin and procalcitonin levels were persistently lower in 28-day survivors and patients with favorable neurologic outcome patients than in 28-day nonsurvivors and patients with unfavorable neurologic outcome. On days 0, 1, and 3, different cut-off values of presepsin showed prognostic value for 28-day mortality and favorable neurologic outcomes similar to procalcitonin. CD14 and human leukocyte antigen-DR expression on monocytes were analyzed by flow cytometry. Compared with controls, CD14 expression in out-of-hospital cardiac arrest patients increased on day 1 and began to decrease on day 3, whereas human leukocyte antigen-DR+ monocyte percentages decreased on days 1 and 3. Presepsin and procalcitonin had a low positive correlation with CD14 expression and a strong negative correlation with human leukocyte antigen-DR+ monocyte percentages on day 1. CONCLUSIONS Plasma presepsin concentrations are independent prognostic factors for out-of-hospital cardiac arrest patients after return of spontaneous circulation and are correlated with abnormal CD14 and human leukocyte antigen-DR expression on monocytes. Monitoring presepsin levels may be helpful for evaluating the prognosis and impaired innate immune response in the early period after return of spontaneous circulation.
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Oliveira JJ, Karrar S, Rainbow DB, Pinder CL, Clarke P, Rubio García A, Al-Assar O, Burling K, Morris S, Stratton R, Vyse TJ, Wicker LS, Todd JA, Ferreira RC. The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus. Arthritis Res Ther 2018; 20:152. [PMID: 30053827 PMCID: PMC6062988 DOI: 10.1186/s13075-018-1649-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 06/20/2018] [Indexed: 01/01/2023] Open
Abstract
Background The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1). Methods We developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) and healthy donors (n = 504). Samples from systemic sclerosis patients (n = 99) were studied as an autoimmune control. We investigated the correlation between sSIGLEC-1 and both monocyte surface SIGLEC-1 and type I interferon-regulated gene (IRG) expression. Associations of sSIGLEC-1 with clinical features were evaluated in an independent cohort of SLE patients (n = 656). Results Plasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with IRG expression in SLE patients. We found ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLE Disease Activity Index clinical score. Conclusions Our sSIGLEC-1 immunoassay provides a specific and easily assayed marker for monocyte–macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in clinical trials. Electronic supplementary material The online version of this article (10.1186/s13075-018-1649-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- João J Oliveira
- Department of Medical Genetics, JDRF/Wellcome Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
| | - Sarah Karrar
- Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, Great Maze Pond, London, UK
| | - Daniel B Rainbow
- Department of Medical Genetics, JDRF/Wellcome Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.,JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Roosevelt Drive, Oxford, UK
| | - Christopher L Pinder
- Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, Great Maze Pond, London, UK
| | - Pamela Clarke
- Department of Medical Genetics, JDRF/Wellcome Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
| | - Arcadio Rubio García
- Department of Medical Genetics, JDRF/Wellcome Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.,JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Roosevelt Drive, Oxford, UK
| | - Osama Al-Assar
- JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Roosevelt Drive, Oxford, UK
| | - Keith Burling
- NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay Laboratory, Cambridge, UK
| | - Sian Morris
- UCL Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Hospital Campus, Rowland Hill Street, London, UK
| | - Richard Stratton
- UCL Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Hospital Campus, Rowland Hill Street, London, UK
| | - Tim J Vyse
- Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, Great Maze Pond, London, UK
| | - Linda S Wicker
- Department of Medical Genetics, JDRF/Wellcome Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.,JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Roosevelt Drive, Oxford, UK
| | - John A Todd
- Department of Medical Genetics, JDRF/Wellcome Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.,JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Roosevelt Drive, Oxford, UK
| | - Ricardo C Ferreira
- Department of Medical Genetics, JDRF/Wellcome Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. .,JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Roosevelt Drive, Oxford, UK.
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