Angela Tincani

Left ventricular function in rheumatoid arthritis during anti-TNF-α treatment: a speckle tracking prospective echocardiographic study

AIM Rheumatoid arthritis (RA) shows a high risk for cardiovascular disease, including heart failure. Although TNF-α has been implicated in the pathogenesis of myocardial remodelling, TNF-α inhibition did not show any efficacy in patients with advanced heart failure and should be contraindicated in RA with cardiac complications. We aimed to assess global left ventricular (LV) systolic function using global longitudinal strain (GLS) as a measure of myocardial deformation, in a group of RA patients before and during anti-TNF-α treatment. METHODS 13 patients (female:male 7:6) affected by RA were prospectively followed for one year during anti TNF-α treatment. Every subject underwent echocardiography before starting anti-TNF-α drugs and after one year of treatment, to evaluate LV ejection fraction (EF), telediastolic diameter, telediastolic volume and global longitudinal strain (GLS) that was calculated using 2D speckle tracking as the mean GLS from three standard apical views (2, 3 and 4 -chambers). The patients showed a mean age of 43 years at RA onset (SD: 13) and a mean follow-up of 7.3 years (SD: 4.8). Steroid and methotrexate were used in 84.6% and 100%, respectively, in association with etanercept (6 cases), adalimumab (4 cases) and infliximab (3 cases). RESULTS Patients globally showed a normal EF before and after one year of treatment (mean: 65% and 65.7%, respectively). GLS did not differ before or after anti-TNF-α treatment (mean: -15.8% and -16.7%, respectively). CONCLUSION Anti-TNF-α treatment did not significantly modify myocardial contractility after 12 months.

Immunological Abnormalities in the Antiphospholipid Syndrome

Publisher Summary This chapter focuses on various immunological abnormalities in the antiphospholipid syndrome (APS). APS is known to belong to the family of autoimmune diseases, which are characterized by antibodies directed to autoantigens and therefore, called autoantibodies. APS is likely to be occurring when the tolerance to endogenous β2GPI is lost. As in most of the autoimmune diseases, including the organ specific ones, the autoimmune responses can be directed against several autoantigens. Besides β2GPI, other phospholipids binding proteins have been investigated as possible targets for aPL, which include autoantibodies to prothrombin (PT), protein C and protein S (PC and PS), thrombomodulin (TM), Annexin V (AV), and high molecular weight kininogen. A peculiar kind of aPL antibodies directed to zwitterionic phospholipid such as phosphatidylcoline (PC) of IgM isotype, belonging to the category of natural autoantibodies, is recorded in patients with autoimmune haemolytic anaemia (both idiopathic and within SLE), and is therefore regarded as a peculiar aspect of APS. A subset of antinuclear antibodies directed to nuclear lamins are identified in primary APS patients and may justify, at least in part, the high prevalence of ANA reported in such disease. Antilamin Bl is strongly associated to APS both primary and within LLD or SLE. The subset of the patients with anti-lamin B1 and LA antibodies have a significantly lower risk for thrombosis compared to the patients with LA and without anti-lamin Bl antibodies.

Non-organ Specific Autoimmunity Involvement in Cardiovascular Disease

Publisher Summary This chapter focuses on humoral non-organ-specific autoimmune pathogenic mechanisms affecting different anatomical cardiac structures in patients suffering from systemic autoimmune diseases. Pericarditis and pericardial effusion are the most frequent cardiac manifestations in systemic autoimmune diseases. Immune complex deposition is the main pathogenic mechanism, at least in systemic lupus erythematosus (SLE), SLE-like diseases and some vasculitides. In scleroderma (SSc), no obvious pathogenic mechanism has been substantiated. Endocardial fibroelastosis (EFE) is a rare and poorly understood disease of the endo-myocardium. The pathologic features consist of collagen and elastin deposition, ventricular hypertrophy, and diffuse endocardial thickening. Its etiopathogenesis remains unclear, but it has been suggested that EFE may be secondary to an autoimmune process. Epidemiological studies showed an increase of cardio- and cerebro-vascular events in patients suffering from systemic autoimmune diseases, such as SLE and rheumatoid arthritis (RA). Moreover, autopsy studies have pointed out that an accelerated atherosclerotic process is largely responsible for such manifestations.

Antiphospholipid/Endothelial Cell Interaction in the Pathogenesis of the Antiphospholipid Syndrome

Publisher Summary This chapter focuses on the interaction between the antiphospholipid (APL) and endothelial cells (EC) in the pathogenesis of the antiphospholipid syndrome (APS). The first report that found a relationship between aPL and EC showed that lupus anticoagulant (LA) positive plasmas suppress prostacyclin (PGI2) release by vascular endothelium, and the imbalance between endothelial PGI2 and platelet thromboxane (TXA2) was suggested to support the in vivo thrombotic diathesis. There is evidence that aPL particularly anti-P2GPI antibodies, can affect endothelium both in vitro and in vivo. The EC activation might also have a gong effect on the other cell types, such as leukocytes and platelets. Due to the interplay between endothelium and these cells, the EC activation is likely able to favor their triggering that evidently is another pro-coagulant effect. The thrombotic manifestations of APS are widespread through all the anatomical districts, although some venous and arterial sites are more frequently affected. Being the aPL reactivity with the endothelium a general pathogenic mechanism, it is apparently in clash with the heterogeneity of the APS clinical manifestations. It has been recently reviewed that ECs functions and responses even to the same stimuli can be modulated differently by the adjacent cell types. Thus, it is not surprising that the anti-β2GPI can induce different effects in different anatomical sites.

Clinical and Prognostic Significance of Non-criteria Antiphospholipid Antibody Tests

Classification criteria for antiphospholipid syndrome (APS) require IgG and IgM isotypes of the anticardiolipin antibodies (aCL), anti-β2 glycoprotein I antibodies (aβ2GPI), and/or the lupus anticoagulant (LA) to satisfy the laboratory criterion for disease definition. However, over the past 20 years, several other non-criteria antiphospholipid antibodies (aPL) directed to other proteins of the coagulation cascade (i.e., prothrombin and/or phosphatidylserine–prothrombin complex), to some domains of β2GPI, or to the anticoagulant activity of annexin A5, have been proposed. The Laboratory Diagnostics Task Force at the 14th International Congress on aPL (Rio de Janeiro, Brazil, 2013) highlighted several non-criteria assays. However, there was consensus that further studies are necessary to obtain high-quality evidence defining their role as risk predictors. The task force reviewed the literature and conducted new studies between 2013 and 2016; the conclusions were presented at a special session during the 15th International Congress on aPL (www.apsistanbul2016.org, North Cyprus, September 2016). This paper updates our recommendations.