BackgroundCardiac manifestations in systemic sclerosis (SSc) can be either due to the fibrotic and vascular process or secondary to pulmonary arterial hypertension (PAH), cardiac inflammation, or renal crisis. Despite being one of the leading causes of death in SSc, cardiac involvement and its therapeutic options have been poorly studied. According to the ACR/EULAR recommendations, therapy with cyclophosphamide (CP) is applied to patients with cardiac manifestations. However, in case of inadequate response to CP, there are no other therapeutics evaluated.ObjectivesThe aim of this retrospective analysis was to explore the efficacy of a therapy with rituximab and mycophenolic acid (MPA), especially in cases of CP failure or therapy induced cardiac toxicityMethods14 Patients with SSc and cardiac involvement (defined as troponin T elevation plus right- or left ventricular systolic or diastolic dysfunction, myocarditis, pericarditis, right heart failure secondary to PAH, or arrhythmias) were analysed. Two patients each showed concomitant myositis and rheumatoid arthritis, respectively. Twelve patients were initially treated with CP and two patients with methotrexate (MTX). Due to a disease progress (either cardiac involvement, skin fibrosis or lung function) a therapy with rituximab and MPA was initiated [1] These patients were followed for up to five years.ResultsBefore initiation of CP or MTX electrocardiogram showed arrhythmias (atrial fibrillation, conduction blocks, multifocal ventricular extrasystoles (VES)) in 9 patients. Echocardiography revealed abnormalities in 10 patients including reduced left-ventricular ejection fraction (LV-EF), diastolic dysfunction, mitral regurgitation, or aortic aneurysm. 3 patients had PAH, 2 patients were diagnosed with post capillary pulmonary hypertension. Cardiac MRI revealed signs of myocarditis in 4 patients. 4 patients required cardiac resynchronization therapy or pacemaker implantation. Moreover, body plethysmography showed a reduction in forced vital capacity (FVC) in 12 patients, suggestive of restrictive lung disease. Under therapy with CP 11 patients had suffered from disease progress, 1 patient developed relapsing pneumonias and the 2 patients with overlap rheumatoid arthritis developed cardiac disease manifestations on MTX monotherapy. Consequently, rituximab 1000 mg q12weeks and MPA 1000 mg bid were initiated. Under this combination troponin T decreased in all patients (p=0.0002), LV-EF improved in 5, remained normal in 7 and deteriorated in 2 patients. The rate of VES improved in 8 patients. In one patient, myocarditis resolved completely (MRI). Moreover, pulmonary artery systolic pressure, measured by echocardiography, improved in all patients diagnosed with PAH under stable therapy. The modified Rodnan skin score improved in all patients, FVC improved in 7 patients, remained stable in 6 and decreased in the patient with overlap myositis. Rituximab infusions could be extended (1000 mg q24weeks) after 24-36 months of treatment in 11 patients. All patients showed peripheral blood depletion of B cells without noticed severe IgG deficiency. While 11 patients did not develop severe complications 2 patients died during follow-up of pneumonia and cardiogenic shock (overlap myositis), respectively and one patient developed a relapse of lung cancer with cerebral metastasis.ConclusionTherapy with rituximab and MPA is a promising alternative. However, its use requires risk stratification of patients with respect to adverse side effects which needs to be explored in future studies.References[1]Rimar D, Rosner I, Slobodin G. Upfront Combination Therapy With Rituximab and Mycophenolate Mofetil for Progressive Systemic Sclerosis. J Rheumatol 2021;48:304–5. https://doi.org/10.3899/jrheum.200484.Disclosure of InterestsNone declared
BackgroundIn acute COVID-19 infection, growing evidence hints towards a broad activation of plasma cells and the presence of pathologic autoantibodies (abs). A systematic screening for abs confirmed induction of diverse functional abs by SARS-CoV-2 infection (1, 2). Immune-mediated thrombosis, involving platelet activation, has been identified as one of the key pathogenic mechanisms in COVID-19 and is linked to morbidity and mortality (3). As natural abs against G protein-coupled receptors, functional abs against the thrombin receptor type-1 (PAR-1) might predispose for increased activation of the coagulation system present in COVID-19 infection.ObjectivesThe aim of this study is to identify the diagnostic value of anti-PAR1 antibodies and their capacity to predict the outcome of COVID-19 infection.Methods82 serum samples from 55 individuals with COVID-19 derived from three different hospitals in Schleswig-Holstein, Germany, and 88 single time point samples from healthy controls were subjected to ELISA-based quantification of anti-PAR-1 abs (CellTrend GmbH Luckenwalde, Germany). The levels of anti-AT1R abs were compared with clinical and laboratory parameters.ResultsCOVID-19 patients revealed markedly increased levels of circulating anti-PAR1 abs in hospitalized patients particularly in those required intensive care treatment in comparison to controls (p < 0.0001, Figure 1a). Anti-PAR1 ab levels were highest in patients with fatal outcome (p = 0.006, Figure 1a). Receiver operating characteristic (ROC) analysis of PAR1 abs levels in COVID-19 patients revealed a sensitivity of 84.00% and a specificity 79.25% for patients requiring intensive care unit (ICU) treatment and a sensitivity of 87.50 % and a specificity 84.51 % to distinguish fatal vs. non-fatal disease outcome (Figure 1b). We found correlation of circulating anti-PAR1 abs with D dimers.Figure 1.Levels of anti-PAR-1 abs in healthy controls (HC) versus COVID-19 positive patients with different disease severity and in non survivors (left). ROC curves are shown to discriminate patients requiring intensive care unit (ICU) or survivors in COVID-19 infection.ConclusionThe increased anti-PAR1 abs, their prediction to identify patients requiring ICU and fatal outcome, and the correlation with markers for blood clotting suggest a role for antibodies against PAR1 in the disease development of blood clotting in COVID-19.References[1]Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020: 370(6515).[2]Wang EY, Mao T, Klein J, et al. Diverse functional autoantibodies in patients with COVID-19. Nature 2021.[3]Bonaventura A, Vecchie A, Dagna L, et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol 2021: 21(5): 319-329.Disclosure of InterestsNone declared
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.