Low serum level of citrullinated histone H3 in patients with dermatomyositis.

OBJECTIVES: We aimed at analyzing the serum levels of citrullinated histone H3 (CitH3) in patients with dermatomyositis (DM) and their association with disease activity. METHODS: Serum CitH3 levels were measured using enzyme-linked immunosorbent assays in serum samples obtained from 93 DM patients and 56 healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminant capacity of CitH3 and other disease variables. The association between CitH3 and disease variables was analyzed using Pearson's rank correlation. RESULTS: Serum CitH3 level was significantly lower in DM patients than in HCs (p < 0.001). The ROC curve analysis revealed that CitH3 strongly discriminated DM patients from HCs (area under the curve [AUC], 0.86), and a combination of CitH3 and the ratio of neutrophil to lymphocyte counts (NLR) showed a greater diagnostic value (AUC, 0.92). Serum CitH3 levels were markedly lower in DM patients with normal muscle enzyme levels than in HCs (all p < 0.001), and when compared to an elevated group, the CitH3 levels were comparable (all p > 0.05). The CitH3 levels showed no difference between DM in active and remission groups. However, in a paired test with 18 hospitalized DM patients, the CitH3 levels were higher in remission state than in active state. Moreover, the CitH3 levels showed no correlation with disease variables that were associated with the disease activity of DM. CONCLUSIONS: Serum CitH3 level may serve as a useful biochemical marker for screening patients with DM from HCs, while its role in monitoring DM disease activity requires further research.

Assessment of the role of neutrophil extracellular traps in SARS-CoV-2 pneumonia.

BACKGROUND: Abnormal neutrophil extracellular traps are associated with lung diseases, thrombosis, increased mucosal secretion in the airways. The aim of this study is to evaluate the possible place of the most specific NETosis marker Cit-H3 protein in diagnostic algorithms by revealing its relationship with the severity, mortality and prognosis of SARS-CoV-2 pneumonia. PATIENTS AND METHODS: Patients (n = 78) who applied to the Emergency Department between March 11, 2020 and June 10, 2020, with positive SARS-CoV-2 polymerase chain reaction (PCR) test and lung involvement were included in the prospective study. Serum Cit-H3 levels and critical laboratory parameters were measured at baseline on the day of clinical deterioration and before recovery/discharge/death. Cit-C3 levels were determined by enzyme immunassay method. RESULTS: Cit-H3 levels in patients with SARS-CoV-2 pneumonia during their first admission to the hospital were significantly higher compared to the healthy control group (p < 0.05). Repeated measurements of Cit-H3 levels of the patients significantly correlated with D-dimer, procalcitonin, Neutrophil/ Lymphocyte ratio, lymphocyte, CRP, and oxygen saturation. Cit-H3 levels of the patients who died were significantly higher than that of those who survived (p < 0.05). Cit-H3 levels were found to be statistically significantly higher in patients who developed acute respiratory distress syndrome, were admitted to the intensive care unit, and had mortality (p < 0.05). CONCLUSIONS: Cit-H3 plays a role in inflammatory processes in SARS-CoV-2 pneumonia, and changes in serum Cit-H3 levels of these patients can be used to determine prognosis and mortality (Tab. 5, Fig. 1, Ref. 21).

High Circulating Levels of Neutrophil Extracellular Traps Parameters Predicting Poor Outcome in COVID-19.

OBJECTIVE: Exploration of biomarkers to predict the severity of COVID-19 is important to reduce mortality. Upon COVID-19 infection, neutrophil extracellular traps (NET) are formed, which leads to a cytokine storm and host damage. Hence, the extent of NET formation may reflect disease progression and predict mortality in COVID-19. METHODS: We measured 4 NET parameters - cell-free double stranded DNA (cell-free dsDNA), neutrophil elastase, citrullinated histone H3 (Cit-H3), and histone - DNA complex - in 188 COVID-19 patients and 20 healthy controls. Survivors (n=166) were hospitalized with or without oxygen supplementation, while non-survivors (n=22) expired during in-hospital treatment. RESULTS: Cell-free dsDNA was significantly elevated in non-survivors in comparison with survivors and controls. The survival rate of patients with high levels of cell-free dsDNA, neutrophil elastase, and Cit-H3 was significantly lower than that of patients with low levels. These three markers significantly correlated with inflammatory markers (absolute neutrophil count and C-reactive protein). CONCLUSION: Since the increase in NET parameters indicates the unfavourable course of COVID-19 infection, patients predisposed to poor outcome can be rapidly managed through risk stratification by using these NET parameters.

Increased serum citrullinated histone H3 levels in COVID-19 patients with acute ischemic stroke.

Background and purpose: Prevalence of acute ische-mic stroke (AIS) is increased in patients with coronavirus disease 2019 (COVID-19). A proposed hypothesis is increased virus-induced propensity to hypercoagulation resulting in arterial thrombosis. Our aim was to provide evidence regarding the involvement of neutrophil extracellular trap (NET) formation (NETosis) in COVID-19 related AIS. Methods: Twenty-six consecutively enrolled COVID-19+ pneumonia patients with AIS, 32 COVID-19+ pneumonia patients without AIS and 24 AIS patients without COVID-19 infection were included to the study. Clinical characteristics of recruited patients were collected. Serum levels of citrullinated histone H3 (H3Cit; a factor of NETosis), IL-8 and C5a (mediators associated with NETosis) were measured by ELISA (enzyme-linked immunosorbent assay). Results: H3Cit levels were significantly higher in COVID-19+ AIS patients, whereas all study groups showed comparable IL-8 and C5a levels. There were no significant differences among etiological subgroups of AIS patients with or without COVID-19. AIS patients with COVID-19 showed relatively increased white blood cell, lymphocyte, neutrophil, D-dimer, C-reactive protein and procalcitonin levels than control groups. H3Cit levels did not correlate with clinical/prognostic features and inflammation parameters. H3Cit and IL-8 levels were correlated in COVID-19 patients without stroke but not in COVID-19 positive or negative AIS patients. Conclusion: Increased levels of inflammation parameters and H3Cit in COVID-19 related AIS suggest that NETosis may cause susceptibility to arterial thrombosis. However, H3Cit levels do not correlate with clinical severity measures and inflammation parameters diminishing the prognostic biomarker value of NETosis factors. Moreover, the link between IL-8 and NETosis appears to be abolished in AIS.