A cytokine/PTX3 prognostic index as a predictor of mortality in sepsis

Davoudian, Sadaf; Piovani, Daniele; Desai, Antonio; Mapelli, Sarah N.; Leone, Roberto; Sironi, Marina; Valentino, Sonia; Silva-Gomes, Rita; Stravalaci, Matteo; Asgari, Fatemeh; Madera, Alessandra; Piccinini, Daniele; Fedeli, Carlo Mario; Comina, D.P.; Bonovas, Stefanos; Voza, Antonio; Mantovani, Alberto; Bottazzi, Barbara

doi:10.3389/fimmu.2022.979232

Cited by 12 publications

(3 citation statements)

References 110 publications

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“…Of note, one innate immune system protein called pentraxin 3 (PTX3) was recently assessed for its potential as a biomarker for early sepsis [120][121][122][123]. PTX3 is an acute-phase reactant that is highly expressed by phagocytes (such as monocytes/macrophages) following pro-inflammatory responses by the immune system [124]. PTX3 expression was reported in many studies to be upregulated in septic patients compared with non-septic patients, and this increase correlated with clinical severity and unfavorable prognosis [120][121][122][123][124][125][126].…”

Section: Biomarkersmentioning

confidence: 99%

Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

Padovani,

Yin

2024

Biomedicines

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Severe infection can lead to sepsis. In sepsis, the host mounts an inappropriately large inflammatory response in an attempt to clear the invading pathogen. This sustained high level of inflammation may cause tissue injury and organ failure. Later in sepsis, a paradoxical immunosuppression occurs, where the host is unable to clear the preexisting infection and is susceptible to secondary infections. A major issue with sepsis treatment is that it is difficult for physicians to ascertain which stage of sepsis the patient is in. Sepsis treatment will depend on the patient’s immune status across the spectrum of the disease, and these immune statuses are nearly polar opposites in the early and late stages of sepsis. Furthermore, there is no approved treatment that can resolve inflammation without contributing to immunosuppression within the host. Here, we review the major mechanisms of sepsis-induced immunosuppression and the biomarkers of the immunosuppressive phase of sepsis. We focused on reviewing three main mechanisms of immunosuppression in sepsis. These are lymphocyte apoptosis, monocyte/macrophage exhaustion, and increased migration of myeloid-derived suppressor cells (MDSCs). The biomarkers of septic immunosuppression that we discuss include increased MDSC production/migration and IL-10 levels, decreased lymphocyte counts and HLA-DR expression, and increased GPR18 expression. We also review the literature on the use of specialized pro-resolving mediators (SPMs) in different models of infection and/or sepsis, as these compounds have been reported to resolve inflammation without being immunosuppressive. To obtain the necessary information, we searched the PubMed database using the keywords sepsis, lymphocyte apoptosis, macrophage exhaustion, MDSCs, biomarkers, and SPMs.

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Section: Biomarkersmentioning

confidence: 99%

Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

Padovani,

Yin

2024

Biomedicines

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“…The molecule exerts a role in tissue repair and remodeling, and acts as regulator of complement activation and leukocytes recruitment (9)(10)(11)(12)(13)(14)(15). In addition, PTX3 levels rapidly increase during inflammatory conditions (infectious diseases, sepsis, acute respiratory distress syndrome, cardiovascular diseases), correlating with severity and predicting the risk of mortality (16)(17)(18)(19)(20)(21). Increased levels of PTX3 were also observed in different autoimmune disorders, such as small-vessel vasculitis and rheumatoid arthritis (22-27).…”

Section: Introductionmentioning

confidence: 99%

The crossroad between autoimmune disorder, tissue remodeling and cancer of the thyroid: The long pentraxin 3 (PTX3)

et al. 2023

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Thyroid is at the crossroads of immune dysregulation, tissue remodeling and oncogenesis. Autoimmune disorders, nodular disease and cancer of the thyroid affect a large amount of general population, mainly women. We wondered if there could be a common factor behind three processes (immune dysregulation, tissue remodeling and oncogenesis) that frequently affect, sometimes coexisting, the thyroid gland. The long pentraxin 3 (PTX3) is an essential component of the humoral arm of the innate immune system acting as soluble pattern recognition molecule. The protein is found expressed in a variety of cell types during tissue injury and stress. In addition, PTX3 is produced by neutrophils during maturation in the bone-marrow and is stored in lactoferrin-granules. PTX3 is a regulator of the complement cascade and orchestrates tissue remodeling and repair. Preclinical data and studies in human tumors indicate that PTX3 can act both as an extrinsic oncosuppressor by modulating complement-dependent tumor-promoting inflammation, or as a tumor-promoter molecule, regulating cell invasion and proliferation and epithelial to mesenchymal transition, thus suggesting that this molecule may have different functions on carcinogenesis. The involvement of PTX3 in the regulation of immune responses, tissue remodeling and oncosuppressive processes led us to explore its potential role in the development of thyroid disorders. In this review, we aimed to highlight what is known, at the state of the art, regarding the connection between the long pentraxin 3 and the main thyroid diseases i.e., nodular thyroid disease, thyroid cancer and autoimmune thyroid disorders.

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“…Enhanced expression of PTX3 and correlation with disease activity has been also reported in conditions of vascular inflammation, including giant cell arteritis, Takayasu’s arteritis, and ANCA-associated small vessel vasculitis ( 18 – 21 ). In addition, plasma levels of PTX3 have been reported to predict mortality in several systemic inflammatory conditions, including acute myocardial infarction ( 22 , 23 ) and sepsis ( 24 – 27 ). Overall, these observations led to evaluate the role of PTX3 as prognostic biomarker of SARS-CoV-2 infections.…”

Section: Introductionmentioning

confidence: 99%

Long pentraxin 3 (PTX3) levels predict death, intubation and thrombotic events among hospitalized patients with COVID-19

Lapadula

Leone²,

Bernasconi³

et al. 2022

Front. Immunol.

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BackgroundPTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19.MethodsLevels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method.ResultsUpon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P<0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P<0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median [IQR]: 51.4 [24.6-94.4] versus 21 [13.4-55.2]; P=0.049).ConclusionsHigh PTX3 levels in patients hospitalized with COVID-19 are associated with a worse outcome. The evaluation of this marker could be useful in prognostic stratification and identification of patients who could benefit from immunomodulant therapy.

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A cytokine/PTX3 prognostic index as a predictor of mortality in sepsis

Cited by 12 publications

References 110 publications

Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

The crossroad between autoimmune disorder, tissue remodeling and cancer of the thyroid: The long pentraxin 3 (PTX3)

Long pentraxin 3 (PTX3) levels predict death, intubation and thrombotic events among hospitalized patients with COVID-19

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