Interleukin-18 Is a Potential Biomarker to Discriminate Active Adult-Onset Still’s Disease From COVID-19

Chen, Po-Ku; Lan, Joung‐Liang; Huang, Pei-Ming; Hsu, Jye‐Lin; Chang, Ching-Kun; Tien, Ni; Lin, Hui‐Ju; Chen, Der‐Yuan

doi:10.3389/fimmu.2021.719544

Cited by 31 publications

(30 citation statements)

References 47 publications

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“…A Turkish study extended these findings by showing that galectin-3 levels were significantly increased among patients with severe COVID-19 compared to non-severe cases and that galectin-3 levels were higher in patients with COVID-19 compared to healthy controls (median of severe COVID-19, 415.31 pg/mL; IQR, 122.81-1622.23 vs. median of non-severe, 326.33 pg/mL; IQR, 100.09-1271.04 vs. median of healthy controls 243.13 pg/mL, 166.57-380.41) [101]. Higher levels of galectin-3 among COVID-19 patients were also reported in a rather small Taiwanese study [102].…”

Section: Galectin-3supporting

confidence: 51%

Biomarkers Associated with Cardiovascular Disease in COVID-19

Kaufmann

Ahmed

Burger

et al. 2022

Cells

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Coronavirus disease-19 (COVID-19) emerged late December 2019 in the city of Wuhan, China and has since spread rapidly all over the world causing a global pandemic. While the respiratory system is the primary target of disease manifestation, COVID-19 has been shown to also affect several other organs, making it a rather complex, multi-system disease. As such, cardiovascular involvement has been a topic of discussion since the beginning of the COVID-19 pandemic, primarily due to early reports of excessive myocardial injury in these patients. Treating physicians are faced with multiple challenges in the management and early triage of patients with COVID-19, as disease severity is highly variable ranging from an asymptomatic infection to critical cases rapidly deteriorating to intensive care treatment or even fatality. Laboratory biomarkers provide important prognostic information which can guide decision making in the emergency department, especially in patients with atypical presentations. Several cardiac biomarkers, most notably high-sensitive cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have emerged as valuable predictors of prognosis in patients with COVID-19. The purpose of this review was to offer a concise summary on prognostic cardiac biomarkers in COVID-19 and discuss whether routine measurements of these biomarkers are warranted upon hospital admission.

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Section: Galectin-3supporting

confidence: 51%

Biomarkers Associated with Cardiovascular Disease in COVID-19

Kaufmann

Ahmed

Burger

et al. 2022

Cells

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“…These studies also showed that the serum IL-18 levels in patients with sepsis were approximately 100 pg/mL, which is significantly lower than the levels in AOSD patients. Interestingly, Chen et al recently reported that serum IL-18 levels at the cut-off value 190.5 pg/ml had high discriminative ability for AOSD and coronavirus disease 2019 (COVID-19), with ROC-AUC 0.948, sensitivity 91.3% and specificity 95.8% (34).…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Interleukin-18 as a Diagnostic Biomarker to Differentiate Adult-Onset Still’s Disease With/Without Macrophage Activation Syndrome From Other Secondary Hemophagocytic Lymphohistiocytosis in Adults

et al. 2021

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BackgroundInterleukin (IL)-18 is markedly elevated in systemic inflammatory diseases that cause the ‘cytokine storm’ such as adult-onset Still’s disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The differences in IL-18 between AOSD and HLH, especially in adults, is uncertain. Macrophage activation syndrome (MAS), a form of secondary HLH, is often difficult to differentiate cases of AOSD that include MAS from other secondary HLH. In this case-control study, we investigated whether serum IL-18 levels could be a useful biomarker for the differential diagnosis of AOSD with or without MAS (AOSD group) and other secondary HLH in adults (adult HLH group).Patients and MethodsWe enrolled 46 patients diagnosed with AOSD including 9 patients with MAS and 31 patients in the adult HLH group, which excluded AOSD-associated MAS. The clinical features and laboratory data were compared between the AOSD and adult HLH groups. In addition, we subdivided the AOSD group (with or without MAS) and the adult HLH group (whether lymphoma-associated or not) and compared the four groups. A logistic regression analysis was used to identify factors with high efficacy in differentiating the two groups, followed by a receiver operating characteristic (ROC) curve analysis to evaluate the differential diagnostic ability of IL-18. We analyzed the correlation between IL-18 and various laboratory parameters in the AOSD group.ResultsSerum IL-18 levels of patients in the AOSD groups were significantly higher than those of the adult HLH groups, and were closely correlated with ferritin, soluble interleukin-2 receptor (sIL-2R), and other laboratory data. Univariate and multivariate logistic regression analyses revealed that IL-18, sIL-2R, and ‘arthralgia or arthritis’ are independent factors useful in the differential diagnosis of AOSD from adult HLH. In the differential diagnosis of both groups, the area under the curve obtained from the ROC curve of IL-18 with a cutoff value of 18,550 pg/mL was 0.91 (95% confidence interval 0.83–1.00; sensitivity 90.3%, specificity 93.5%), and the differential diagnosis ability of IL-18 was superior to that of other laboratory data.ConclusionsIL-18 could be a useful biomarker for the differential diagnosis of AOSD and adult HLH.

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“…A recent study reported that Gal-3 levels in macrophages, monocytes, and dendritic cells were increased in patients with severe COVID-19, compared with mild diseases ( Figure 1 ) ( 127 ). Moreover, the serum level of Gal-3 was significantly higher in severe COVID-19 patients, compared with healthy controls ( 69 , 128 ). It has been reported that Gal-3 was upregulated in proliferating T cells in severe cases of COVID-19, and frequently the hyperinflammation phase involves the overexpression of Gal-3, TNF-α, and IL-6 ( 129 ).…”

Section: Immune Checkpoint Ligands In Covid-19mentioning

confidence: 84%

“…Another study observed significant elevations of soluble TIM-3 (sTIM-3) and soluble LAG-3 (sLAG-3) in severe COVID-19 patients, compared with mild disease ( 44 ). Furthermore, Chen et al found that the plasma level of sTIM-3 was significantly higher in severe COVID-19 patients, compared with healthy controls ( 69 ). Moreover, Diao et al showed a significant increase in TIM-3 expression on peripheral blood CD4+ T cells in COVID-19 patients, which could contribute to the functional exhaustion of these cells ( 67 ).…”

Section: Inhibitory Immune Checkpoints In Covid-19mentioning

confidence: 99%

Inhibitory Immune Checkpoint Receptors and Ligands as Prognostic Biomarkers in COVID-19 Patients

2022

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Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. During T-cell activation, the immune system uses different checkpoint pathways to maintain co-inhibitory and co-stimulatory signals. In COVID-19, expression of immune checkpoints (ICs) is one of the most important manifestations, in addition to lymphopenia and inflammatory cytokines, contributing to worse clinical outcomes. There is a controversy whether upregulation of ICs in COVID-19 patients might lead to T-cell exhaustion or activation. This review summarizes the available studies that investigated IC receptors and ligands in COVID-19 patients, as well as their effect on T-cell function. Several IC receptors and ligands, including CTLA-4, BTLA, TIM-3, VISTA, LAG-3, TIGIT, PD-1, CD160, 2B4, NKG2A, Galectin-9, Galectin-3, PD-L1, PD-L2, LSECtin, and CD112, were upregulated in COVID-19 patients. Based on the available studies, there is a possible relationship between disease severity and increased expression of IC receptors and ligands. Overall, the upregulation of some ICs could be used as a prognostic biomarker for disease severity.

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Interleukin-18 Is a Potential Biomarker to Discriminate Active Adult-Onset Still’s Disease From COVID-19

Cited by 31 publications

References 47 publications

Biomarkers Associated with Cardiovascular Disease in COVID-19

Biomarkers Associated with Cardiovascular Disease in COVID-19

Usefulness of Interleukin-18 as a Diagnostic Biomarker to Differentiate Adult-Onset Still’s Disease With/Without Macrophage Activation Syndrome From Other Secondary Hemophagocytic Lymphohistiocytosis in Adults

Inhibitory Immune Checkpoint Receptors and Ligands as Prognostic Biomarkers in COVID-19 Patients

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