ABSTRACT
Background: Pentraxin 3 (PTX3) is an acute phase protein, which regulates the outcomes of inflammation. Currently, there are no myocarditis-typical biomarkers that allow a non-invasive diagnosis, and endomyocardial biopsy (EMB) is still the gold standard. Finally, risk stratification is often challenging in these patients. Aim(s): To investigate whether PTX3 could be expressed in cardiomyocytes and released during myocarditis, serving as a novel and independent diagnostic indicator of myocardial inflammation, and contributing to prognosis prediction. Method(s): Fifty-five patients with a diagnosis of acute or chronic active myocarditis proven by cardiac magnetic resonance (CMR) and/or endomyocardial biopsy (EMB), were included. First, we evaluated tissue PTX3 expression by immunohistochemistry (IHC). Then, we assessed circulating blood PTX3 by ELISA technique. Result(s): On cardiac tissue, PTX3 at IHC did not localize in the interstitium, and showed an inconstant expression in the vascular endothelium, but a marked staining by cardiomyocytes in all myocarditis patients. The only exception was represented by two patients with systemic COVID-19, with SARS-CoV-2 and PVB-19 intracardiac genomes, respectively, who showed a diffuse cardiac PTX3 expression. Remarkably, at semi-quantitative pixel analysis, viral aetiology showed higher levels of tissue expression, rather than the autoimmune one. Circulating PTX3 levels were significantly higher in myocarditis patients than controls, with pathologic values in 87% of myocarditis patients, and none among controls. Remarkably, plasma PTX3 proved to be more sensitive in myocarditis detection than CRP, ESR, troponin T, and NT-proBNP. As regards of prognosis, we observed that patients with heart failure (HF) presentation all had elevated PTX3 levels, as compared with chest pain or arrhythmia. Remarkably, patients with reduced LVEF (<50%) at admission who recovered during follow-up had higher baseline PTX3 levels, rather than those whose systolic function did not improve. Conclusion(s): Tissue PTX3 is mostly expressed by cardiomyocytes in patients with active myocarditis on EMB samples. In addition, plasma PTX3 is a sensitive diagnostic and prognostic marker in patients with inflammatory cardiomyopathy.
ABSTRACT
The cellular responses to the BNT162b2 vaccine and their correlation with antibody titer and gender determinants are critical to assess. We aimed to evaluate the cellular response kinetics, correlating it with gender and antibody titer.Peripheral Blood Mononuclear Cells (PBMC) were stimulated with SARS-CoV-2 Spike protein, and the IFN-gamma was evaluated by Elispot assay at 5 different timepoints, for up to 9 months after the BNT162b2 vaccine. 107 healthcare workers were divided into 4 age groups: <40 and >40 years for men, based on the gradual decline of testosterone with aging;<48 and >48 years for women based on the decrease of estrogen with menopause. Furthermore, seropositive individuals were analyzed at baseline to avoid confounding factors caused by the previous infection with SARS-CoV-2. We also analyzed pre-pandemic samples as controls to consider the cross-reactivity toward other coronaviruses. Among seronegative at baseline, the T-cell response against Sprotein changed from a median of 2 spot forming cells (SFC)/400.000 PBMC (Interquartile range, IQR, 0-17) before vaccination to a median of 42 (17.5-78.0) after the second dose. Then, it progressively decreased to 13 (0-34) at 6 months after vaccination and 11 (0-31) after 9 months. At all timepoints, the differences were statistically significant compared to baseline values. Moreover, the results obtained after the second dose were significantly higher than those observed at any other time point. Indeed, a significant correlation was observed between T-cell response and anti-S antibody titer (p<0.001), previously analyzed, even if it was weak in magnitude (r=0.314). Natural seropositive showed higher T cell response at baseline than seronegative ones (median: 2 vs. 29, p=0.003), even if there were no significant differences in response at later time points. Our data suggest that T-cell reactiveness is poorly impacted by sex and age, whereas age was significantly associated with anti-S antibody titer. T-cell response declines 9 months later administration, indicating a waning of immune response over time. So, the positive correlation with the antibody titer confirms a linkage between different arms of adaptive responses and potentially converts future vaccinations into a tailored process.