Objectives: The relevance of detecting antibodies against anticardiolipin, β2-glycoprotein I (β2gpI) or lupus anticoagulant (LA), collectively called antiphospholipid autoantibodies (APA), in subjects with immune thrombocytopenia (ITP) is still a debated issue. In particular, whether APA profile may affect the clinical course of ITP is unknown. Methods: In this study, we report our experience in a cohort of ITP patients with APA with specific interest to the relevance of different antiphospholipid antibody profiles in clinical outcome and response to treatment. Results: Thirty-seven out of 159 patients (23.2%) fulfilling ITP criteria had a platelet count ≤50 × 10 9 /L and tested positive at APA at ITP onset. Twenty-three (62.1%) patients received at least one line of treatment for ITP. Fourteen subjects (37.8%) showing triple positivity for APA showed a significantly lower median platelet count compared to other APA patients (p = .006). Among these ITP subjects with triple positivity, 85.7% needed a treatment because of low platelet count compared to 47.8% ITP patients with non-triple-positive APA (p = .0094). ITP/APA subjects who received immunosuppressors had a higher rate of thrombosis (p = .024) as well as thrombosis developed in subjects who were on steroid therapy at a significantly higher dosage than subjects who did not develop thrombotic episodes (p < .001). When considering treatment, CR and SR rate were significantly higher in ITP/triple-positive patients compared to non-triple-positive subjects (p = .021 and p = .005). Conclusions: The profile of APA may affect the outcome of patients with ITP.

Idiopathic pulmonary fibrosis (IPF) is mainly characterized by aberrant extracellular matrix deposition, consequent to epithelial lung injury and myofibroblast activation, and inflammatory response. Glycogen synthase kinase 3 (GSK-3) is a serine–threonine kinase involved in several pathways, and its inhibition has been already suggested as a therapeutic strategy for IPF patients. There is evidence that GSK-3 is able to induce matrix metalloproteinase (MMP) expression and that its inhibition modulates MMP expression in the tissues. The aim of our study was to investigate the role of GSK-3 and its inhibition in the modulation of MMP-9 and -2 in an in vivo mouse model of lung fibrosis and in vitro using different cell lines exposed to pro-inflammatory or pro-fibrotic stimuli. We found that GSK-3 inhibition down-modulates gene expression and protein levels of MMP-9, MMP-2, and their inhibitors TIMP-1 and TIMP-2 in inflammatory cells harvested from bronchoalveolar lavage fluid (BALF) of mice treated with bleomycin as well as in interstitial alveolar macrophages and cuboidalized epithelial alveolar cells. To the same extent, GSK-3 inhibition blunted the increased MMP-9 and MMP-2 activity induced by pro-fibrotic stimuli in a human lung fibroblast cell line. Moreover, the αSMA protein level, a marker of fibroblast-to-myofibroblast transition involved in fibrosis, was decreased in primary fibroblasts treated with TGFβ following GSK-3 inhibition. Our results confirm the implication of GSK-3 in lung inflammation and fibrosis, suggesting that it might play its role by modulating MMP expression and activity but also pushing fibroblasts toward a myofibroblast phenotype and therefore enhancing extracellular matrix deposition. Thus, its inhibition could represent a possible therapeutic strategy.

Blockers of the renin-angiotensin system (RAS) have been reported to increase the angiotensin converting enzyme (ACE)2, the cellular receptor of SARS-CoV-2, and thus the risk and course of COVID-19. Therefore, we investigated if angiotensin (Ang) II and RAS blockers affected ACE2 expression and SARS-CoV-2 infectivity in human epithelial bronchial Calu-3 cells. By infectivity and spike-mediated cell–cell fusion assays, we showed that Ang II acting on the angiotensin type 1 receptor markedly increased ACE2 at mRNA and protein levels, resulting in enhanced SARS-CoV-2 cell entry. These effects were abolished by irbesartan and not affected by the blockade of ACE-1-mediated Ang II formation with ramipril, and of ACE2- mediated Ang II conversion into Ang 1-7 with MLN-4760. Thus, enhanced Ang II production in patients with an activated RAS might expose to a greater spread of COVID-19 infection in lung cells. The protective action of Angiotensin type 1 receptor antagonists (ARBs) documented in these studies provides a mechanistic explanation for the lack of worse outcomes in high-risk COVID-19 patients on RAS blockers.

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Currently, enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease’s progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. Several studies reported how secondary biochemical processes beyond Gb3 and lyso-Gb3 accumulation—such as oxidative stress, compromised energy metabolism, altered membrane lipid, disturbed cellular trafficking, and impaired autophagy—might exacerbate Fabry disease adverse outcomes. This review aims to summarize the current knowledge of these pathogenetic intracellular mechanisms in Fabry disease, which might suggest novel additional strategies for its treatment.

Bacterial infections represent life-threatening complications in patients with febrile neutropenia (FN). Biomarkers of infections may help to differentiate bacteraemia from non-bacteraemia FN. We aimed to evaluate the utility of procalcitonin (PCT), presepsin (PS), C-reactive protein (CRP) and interleukin-8 (IL-8) as biomarkers of bacteraemia in adult FN patients with haematological malignancies. Thirty-six FN episodes experienced by 28 oncohematological patients were considered. 11 out of 36 episodes were classified as bacteraemia. PCT was the best biomarker to predict bacteraemia with area under the curve (AUC) ROC of 0,9; while the most sensitive was IL-8 (90,9%) with AUC ROC of 0,88. All patients with PCT concentrations above 1,6 μg/l had bacteraemia. Patients with IL-8 concentrations > 170 pg/ml or PS concentrations superior then 410 pg/ml had 40 times and 24 times higher risk for bacteraemia, respectively. PCT remains better than IL-8 and PS in predicting bacteraemia in adult hematological patients with FN.