Cellular Immunology of Myocarditis: Lights and Shades-A Literature Review.

Myocarditis is an inflammatory disease of the myocardium with heterogeneous etiology, clinical presentation, and prognosis; when it is associated with myocardial dysfunction, this identifies the entity of inflammatory cardiomyopathy. In the last few decades, the relevance of the immune system in myocarditis onset and progression has become evident, thus having crucial clinical relevance in terms of treatment and prognostic stratification. In fact, the advances in cardiac immunology have led to a better characterization of the cellular subtypes involved in the pathogenesis of inflammatory cardiomyopathy, whether the etiology is infectious or autoimmune/immune-mediated.

The Role of the Immune System in Pathobiology and Therapy of Myocarditis: A Review.

The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression.

The Impact of Dupilumab on Work Productivity and Emotional Health in CRSwNP: A Multicentric Study in Northeast Italy.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with Dupilumab in different rhinological units were considered for this study via their evaluation at the baseline at first and the consequential follow-up at 6-, 12-, and 24 months from the first administration.

Patients with antiphospholipid syndrome and a first venous or arterial thrombotic event: clinical characteristics, antibody profiles and estimate of the risk of recurrence.

Objectives: Thrombosis in antiphospholipid syndrome (APS) involves in most cases the venous circulation Why in some patients thrombotic APS affects the arterial circulation and in particular cerebral circulation is unknown. In previous studies, both patient characteristics and antiphospholipid antibody types and titers have been associated with arterial thrombosis. Aim of this study was to compare the clinical characteristics and laboratory findings of venous and arterial thrombotic APS from a large series of patients.

Close link between antiphosphatidylserine/prothrombin antibodies, lupus anticoagulant, and activated protein C resistance in tetra antiphospholipid antibody-positive subjects.

Background: Most of the carriers/patients triple-positive for antiphospholipid antibodies (lupus anticoagulant [LAC], immunoglobulin G [IgG]/immunoglobulin M [IgM] anticardiolipin, and anti-β2-glycoprotein I antibodies) are tetra-positive, being positive for antiphosphatidylserine/prothrombin (aPS/PT) antibodies. The relationship between aPS/PT titer, LAC potency, and resistance to activated protein C (aPC-R) has not been investigated.

Objectives: The aim of this study was to clarify the mutual interdependence of these parameters in tetra-positive subjects.

Fulminant Myocarditis: When One Size Does Not Fit All - A Critical Review of the Literature.

Fulminant myocarditis, rather than being a distinct form of myocarditis, is instead a peculiar clinical presentation of the disease. The definition of fulminant myocarditis has varied greatly in the last 20 years, leading to conflicting reports on prognosis and treatment strategies, mainly because of varied inclusion criteria in different studies. The main conclusion of this review is that fulminant myocarditis may be due to different histotypes and aetiologies that can be diagnosed only by endomyocardial biopsy and managed by aetiology-directed treatment.

Antiphospholipid syndrome: Reversal of antiphosphatidylserine/prothrombin-induced activated protein C resistance.

Background: Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are the major contributor to activated Protein C resistance (APC-R) in tetra-positive thrombotic high-risk patients with Antiphospholipid Syndrome (APS).

Objectives: To evaluate the role of phospholipids (PL) on aPS/PT mediated APC-R.

Patients/methods: Total IgG were purified from plasma of 6 tetra-positive patients and IgG aPS/PT were affinity-purified from 3 of these patients.

Platelet- and endothelial-derived microparticles in the context of different antiphospholipid antibody profiles.

Objectives: Studies on microparticles (MPs) in patients with antiphospholipid antibodies (aPL) are sparse and inconclusive. The relation between MPs and different aPL antibody profiles has never been tested. We evaluated the presence of platelet and endothelial microparticles in patients positive for IgG anti-β2-glycoprotein I (aβ2GPI) antibodies according to triple, double and single positive aPL profiles.

Anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) in isolated lupus anticoagulant (LA): is their presence linked to dual test positivity?

Objectives: Anti phosphatidylserine/prothrombin antibodies (aPS/PT) are often present in patients with antiphospholipid syndrome (APS) and might be relevant in the pathogenesis of this condition. They are major determinant of lupus anticoagulant (LA) in triple-positive antiphospholipid (aPL) profile. Whether they are present and pathogenic in patients with isolated LA [negative anticardiolipin (aCL) and anti β2-glycoprotein I (aβ2GPI) antibodies] is a matter of debate.

Serum Anti-Heart and Anti-Intercalated Disk Autoantibodies: Novel Autoimmune Markers in Cardiac Sarcoidosis.

Background: Sarcoidosis is an immune-mediated disease. Cardiac involvement, a granulomatous form of myocarditis, is under-recognized and prognostically relevant. Anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in nonsarcoidosis myocarditis forms.

Insight into the hypercoagulable state of high-risk thrombotic APS patients: Contribution of aβ2GPI and aPS/PT antibodies.

Objective: Most high-risk thrombotic antiphospholipid syndrome (APS) patients test positive for anti-β2-glycoprotein I (aβ2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Information on the influence of these antibodies on thrombin generation and activated protein C resistance (aPCr) is still sparse and contradictory.

Methods: Plasma of 16 patients poured into a β2GPI affinity column allowed the perfect separation of aβ2GPI and aPS/PT antibodies.

Antibody profiles comprising anti phosphatidylserine/prothrombin differently affect thrombin generation and protein C resistance in antiphospholipid antibody carriers.

Anti phosphatidylserine/prothrombin antibodies (aPS/PT) are currently not included in the laboratory work-up of antiphospholipid symdrome (APS). However, several studies indicate that aPS/PT confer additional risk for thromboembolic events when added to classical antiphospholipid (aPL) antibody panel. We aimed to study thrombin generation (TG), a test that describes hyper or hypo-coagulability, in a cohort of antiphospholipid antibody (aPL) carriers with or without aPS/PT.

Prothrombin Is Responsible for the Lupus Cofactor Phenomenon in a Patient with Lupus Anticoagulant/Hypoprothrombinemia Syndrome.

Lupus anticoagulant is a misnomer as it is commonly associated with thromboembolic events. In few cases, the name retains its literal meaning when it characterizes patients with a bleeding disorder. We describe a patient with lupus anticoagulant, hypoprothrombinemia, and major bleeding (lupus anticoagulant/hypoprothrombinemia syndrome).

Tetra positive thrombotic antiphospholipid syndrome: Major contribution of anti-phosphatidyl-serine/prothrombin antibodies to lupus anticoagulant activity.

Background: The concurrent presence of lupus anticoagulant, anticardiolipin, and anti β2-glycoprotein I antibodies (triple positive profile) identifies patients at high risk of thromboembolic events. These patients are also positive for anti-phosphatidyl-serine/prothrombin antibodies (tetra-positive profile).

Objective: Understand which antibody among anti-β2-glycoprotein I and anti-phosphatidyl-serine/prothrombin is responsible for lupus anticoagulant activity.

An in vitro model to mimic the thrombotic occlusion of small vessels in catastrophic antiphospholipid syndrome (CAPS).

Platelet activation and decrease in platelet count characterize the development of the most feared form of antiphospholipid syndrome (APS), i.e. catastrophic APS (CAPS).

Comparison of real world and core laboratory lupus anticoagulant results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository.

Background: Variability remains a challenge in lupus anticoagulant (LA) testing.

Objective: To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry.

Methods: Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation.

Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns.

Background: Whether antibodies directed to β2-Glycoprotein I (aβ2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown.

Objective: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aβ2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients.

Clinical value of anti-domain I-β2Glycoprotein 1 antibodies in antiphospholipid antibody carriers. A single centre, prospective observational follow-up study.

Background: There seems to be a clear correlation between antibodies against domain I (anti-DI) of β2Glycoprotein I and severe clinical profiles in antiphospholipid syndrome (APS) patients. We investigated the clinical significance of anti-DI antibodies in a cohort of aPL carriers.

Methods: One hundred and five carriers persistently positive for IgG anti-β2Glycoprotein 1 antibodies (a-β2GPI) and/or IgG anticardiolipin (aCL) and/or lupus anticoagulants (LAC) were tested for the presence of anti-DI antibodies using the QUANTA Flash® Beta2GPI-Domain I chemiluminescence immunoassay.

Thrombocytopenia in high-risk patients with antiphospholipid syndrome.

Unlabelled: Essentials The prevalence of thrombocytopenia in patients with antiphospholipid syndrome is not well defined. We studied triple positive patients with antiphospholipid syndrome and its catastrophic variant. Prevalence of thrombocytopenia was 6% and 100% in patients who developed the catastrophic form.

Lupus Anticoagulant Testing: Diluted Russell Viper Venom Time (dRVVT).

Diluted Russell Viper Venom Time (dRVVT) has become the most popular test to detect Lupus Anticoagulant (LA). dRVVT is more sensitive than other global tests employed to detect LA and is not affected by inhibitors of factor VIII or IX. The test is most successfully implemented if you observe three steps in its execution: screening, mixing, and confirmatory studies.

Laboratory Diagnostics of Antiphospholipid Syndrome.

Diagnosis of antiphospholipid syndrome (APS) lies in the recognition of antiphospholipid antibodies (aPL). As standardization of tests for the detection of aPL is far from being optimal and reference material is not available, inappropriate diagnoses of APS are not unusual. In the last few years, the concept of triple test positivity has emerged as a useful tool to identify patients with APS.