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
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
Contact Tracing Apps (CTAs) have been developed to contain the coronavirus disease 19 (COVID-19) spread. By design, such apps invade their users' privacy by recording data about their health, contacts, and-partially-location. Many CTAs frequently broadcast pseudorandom numbers via Bluetooth to detect encounters. These numbers are changed regularly to prevent individual smartphones from being trivially trackable. However, the effectiveness of this procedure has been little studied.We measured real smartphones and observed that the German Corona-Warn-App (CWA) exhibits a device-specific latency between two subsequent broadcasts. These timing differences provide a potential attack vector for fingerprinting smartphones by passively recording Bluetooth messages. This could conceivably lead to the tracking of users' trajectories and, ultimately, the reidentification of users. CCS CONCEPTS• Security and privacy → Pseudonymity, anonymity and untraceability.
BackgroundPsoriatic arthritis (PsA) is a chronic inflammatory disease that affects the skin, nails, tendons and joints. In addition, several comorbidities have been identified with PsA. In particular, a frequent occurrence of fatigue and mental disorders such as depression have been described in patients with PsA. Key cellular players in pathophysiology of PsA are T cells. However, in recent years, various autoantibodies such as anti-LL37 and anti-Pso-p27 have been identified in PsA as well [1]. Autoantibodies targeting G protein-coupled receptors (GPCRs) have been identified in several diseases and are involved in disease pathophysiology [2]. Many of these autoantibodies are agonists that enhance the effect of the natural ligand at the receptor [3].ObjectivesThe aim of this study was to investigate the association between autoantibodies directed to distinct GPCRs and disease activity as well as comorbidities in PsA.MethodsIn a prospective observational study forty-five patients with an active PsA according to CASPAR criteria and 24 healthy controls (HCs) matched according to age and sex were included in this study. The serum-concentrations of 20 autoantibodies directed to GPCRs involved in the renin-angiotensin-aldosterone system, the sympathetic and parasympathetic nervous system as well as chemokine, complement and scavenger receptors, were measured by the company CellTrend GmbH (Luckenwalde, Germany). Autoantibodies measured in patient’s sera at baseline were transformed and adjusted for age as confounder for further analyses. To compare autoantibody concentrations between PsA and HCs we applied Two-Way-ANOVA. Correlation analyses were performed using Pearson correlation. Autoantibody concentrations between patients with and without depression were analyzed by Student’s T test and binary logistic regression.ResultsPatients were equally distributed according to sex (male 51.1%, female 48.9%) and of a mean age of 47.5 ± 13.2 years. Mean arthritic disease manifestation assessed by DAPSA was 44.4 ± 21.2. Patients displayed a disease activity with a mean PASI of 6.19 ± 6.33, and high impact on patient reported outcomes with a mean DLQI of 10.3 ± 7.4 and a mean HAQ of 1.0 ± 0.8. Autoantibody concentrations did not differ significantly between patients with PsA and HCs. Further analysis revealed significant correlations between autoantibody levels, disease activity scores and treatment response of cutaneous disease manifestation after 16 weeks of treatment (Δ PASI),Figure 1. Moreover, the levels autoantibodies directed to the MAS receptor, CXCR3, PAR1 and stabilin were significantly higher in patients with PsA suffering from depression compared to patients without depression (MASR: p=0.035; CXCR3: p=0.011; PAR1: p=0.047; stabilin: p=0.035), although binary logistic regression did not prove any predictive value for these four antibodies.ConclusionAutoantibodies directed to GPCRs correlated with disease activity scores in patients with PsA. Further larger analyses regarding the functional role of these autoantibodies in PsA are required.References[1]Koussiouris J, Chandran V. Autoantibodies in Psoriatic Disease. The Journal of Applied Laboratory Medicine (2022) 7:281–293. doi: 10.1093/jalm/jfab120[2]Skiba MA, Kruse AC. Autoantibodies as Endogenous Modulators of GPCR Signaling. Trends in Pharmacological Sciences (2021) 42:135–150. doi: 10.1016/j.tips.2020.11.013[3]Yue X, Yin J, Wang X, Heidecke H, Hackel AM, Dong X, Kasper B, Wen L, Zhang L, Schulze-Forster K, et al. Induced antibodies directed to the angiotensin receptor type 1 provoke skin and lung inflammation, dermal fibrosis and act species overarching. Ann Rheum Dis (2022)annrheumdis-2021-222088. doi: 10.1136/annrheumdis-2021-222088Figure 1.Heatmap displaying Pearson’s correlation coefficient of correlation analyses between diseases activity scores and autoantibody concentrations adjusted for age at baseline. Pearson correlation analyses with a p-value <0.05 are marked with a box.Acknowledgements:NIL.Disclosure of InterestsHanna Grasshoff Speakers bureau: Abbvie, Sara Comduehr: None declared, Justus Ohmes: None declared, Diamant Thaçi Speakers bureau: Diamant Thaçi has received honoraria as an advisor, speaker and/or investigator from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Regeneron, Roche-Possay, Samsung, Sanofi and UCB., Consultant of: Diamant Thaçi has received honoraria as an advisor, speaker and/or investigator from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Regeneron, Roche-Possay, Samsung, Sanofi and UCB, Kai Schulze-Forster Shareholder of: board of management: CellTrend, Harald Heidecke Shareholder of: board of management: CellTrend, Peter Lamprecht: None declared, Gabriela Riemekasten: None declare.d.
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