Features of Cognitive Dysfunction in Patients with Systemic Lupus Erythematosus

The purpose of the study was to explore the structure of cognitive impairment in patients with systemic lupus erythematosus and to determine the factors associated with its development. Materials and methods. Advanced examination of 64 patients with systemic lupus erythematosus was carried out. Neurological disorders were diagnosed in 54 patients (84.38% of patients). These patients were included in the main study group (group 1). In 10 (15.62% of patients) patients, these manifestations were not found and they entered the control group (group 2). The object of the study was cognitive impairment in patients with systemic lupus erythematosus. To assess the cognitive status of patients, the Montreal Cognitive Assessment Scale was used, a widely used questionnaire that evaluates cognitive functions across multiple domains. The laboratory study included blood tests to identify the type and titer of antinuclear antibodies, lupus anticoagulant, and antiphospholipid antibodies, in particular, anti-cardiolipin antibodies. Results and discussion. It was found that the complaints that patients usually present to describe impaired cognitive functions (such as "memory deterioration", "memory impairment", "decreased attention", "difficulty concentrating", etc.) were among the most common in patients with systemic lupus erythematosus. Thus, complaints of memory impairments were expressed by 37 patients (57.81% CI 45.71-69.91), impaired attention and concentration – 41 patients (64.06% CI 52.31-75.82), and between these complaints a strong correlation was established (r = 0.83; p <0.001). The results of the examination of patients using the Montreal Cognitive Assessment Scale showed that the average indicator among all examined is 25.0 (22.0; 27.5) points in the main group – 24.0 (22.0; 26.0) points, which is statistically significantly less (p <0.001) compared with the control group – 28.0 (27.0; 29.0) points. It was found that among patients who scored less than 26 points on the Montreal Cognitive Assessment Scale, there was a statistically significant decrease in indicators in the domains of memory, attention, and speech (p <0.001). It was found that there is a correlation between the presence of anti-cardiolipin antibodies with CD (determined by the Montreal Cognitive Assessment Scale) (rs = -0.56; p <0.001), the same correlation was found in relation to lupus anticoagulant (rs = -0.56; p <0.001). Conclusion. Cognitive dysfunction is one of the most common neurological manifestations of systemic lupus erythematosus. Among the examined patients, decrease in indicators in the domains of memory, attention and speech is the most often observed. Cognitive dysfunction may be associated with the production of certain classes of autoantibodies: antiphospholipid antibodies (in particular, anti-cardiolipin antibodies) and lupus anticoagulant

AB0696 ANTI-PHOSPHOLIPID AUTOANTIBODIES IN COVID-19 PATIENTS

Background:Because of the inflammation boosting cytokines, Coronavirus disease 2019 (COVID-19) has demonstrated thrombotic consequences that have increased its morbidity and mortality. There is evidence that mechanisms that contribute in thrombosis in COVID-19 patients are similar to those in anti-phospholipid syndrome (aPS). In fact, there is a possibility that anti-phospholipid autoantibodies (aPLs) might impulse thrombosis in patients with COVID-19, as literature suggests2.Objectives:The aim of our study was to evaluate the anti-phospholipid autoantibody titre in patients with COVID-19 during and after the infection.Methods:This is an observational study which included 71 patients with a recent COVID-19 up to 4 weeks after. Every patient was completed with aPL titre about IgG and IgM anti-cardiolipine (ACA) and lupus anticoagulant (LAC) autoantibodies. According to titre results, the patients were divided into groups in order to better show the immunologic results.Results:After gathering and analysing the data, it was estimated that 21 patients (29.6%) were positive for at least one type of aPL antibody: 12 patients were found positive for lupus anticoagulant autoantibodies (57.1%), 6 patients were double positive for LAC and ACA (28.6%), and 3 patients were positive for anti-cardiolipin antibodies (14.3%). Seven patients were IgM positive for any aPL (33.3%), 6 patients were found to have positive IgM and IgG (28.6%) and 8 patients had only IgG antibodies (38.1%).Conclusion:From this study it was observed that a significant proportion of patients with recent COVID-19 infection had positive anti-phospholipid antibodies, compared to the general population prevalence. This suggests that the impact of aPLs in COVID-19 might be of great importance. It should be carefully evaluated in order to better understand the mechanisms of thrombotic complications.References:[1]Wise Jacqui. Covid-19 and thrombosis: what do we know about the risks and treatment? BMJ 2020; 369:m2058[2]Zuo, Yu, et al. “Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19.” Science translational medicine 12.570 (2020).Disclosure of Interests:None declared

AB0078 LIPID IMMOBILIZATION AS A METHOD TO OBTAIN ANTIGENIC NANO-OBJECTS

Objectives:Objective of the study is to research the effect of emulsion polymerization on active sites of cardiolipin antigen determinant in antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE).Methods:Having integrated antigen nanoobjects we developed immobilized magnetocontrollable antigen nanosystems and put them to an evaluation test. The nanosystems are polyacrylamide granules with a built in antigen. To obtain stable immobilized multi–use biopharmaceuticals with targeted properties (shape, particle diameter, pore size, density) we used a modified version of emulsion polymerization method using polyacrylamide carrier gel. This method permitted a greater sorptive capacity, preserving the antigen in maximum native state, and opened up the possibility of controllable modification of nanoobjects. Cardiolipin was used as the antigen in question.Results:Following the method described above we performed sorption of anticardiolipin antibodies from blood plasma of SLE patients who showed clinical presentations of antiphospholipid syndrome. Blood serum from 10 apparently healthy individuals served as control. The level of cardiolipin antibodies was determined before and after sorption by indirect solid phase immunoenzyme method. In the eluate we estimated total protein by Lowry method. In vitro testing showed that the obtained antigen nanosystems based on immobilized cardiolipin could effectively remove cardiolipin antibodies from whole blood of SLE patients with clinical presentations of APS to achieve the values of healthy individuals (before sorption cardiolipin antibodies 0.328 ± 0.028; after sorption 0.059 ± 0.017; p<0.001; sorption capacity 8.00 ± 0.390 mg/ml).Conclusion:The method of emulsion polymerization with consideration to hydrophobic and hydrophilic properties of lipid molecules permits obtaining and modifying biomolecules with certain properties, in a controlled fashion.Disclosure of Interests:None declared

MTHFR 677 C< T and 1298 A>C polymorphisms increases the risk of recurrent abortion in the Iraqi woman

Background: The C677T and A1298C polymorphism mutations in the methylenetetrahydrofolate reductase (MTHFR) gene will be investigated in a multi-abortion study. Aim: To determine mutation (SNP) in the methyl tetrahydrofolate reductase (MTHFR) Gene with multiple abortion. Methods: “We nominated two hundred patients for this study in three groups: the study group, The first group included 50 women with a history of 1 or 2 missed first trimester Abortions and fifty to control group the last group which consisted of one hundred Patients with a history more than two missed abortion. Anticoagulants human blood tests such as (protein C, protein S, and lupus) as well as general serum tests IgG and IgM for (Cytomegalovirus, Toxoplasma gondii, Rubella virus, Anti-cardiolipin antibodies and anti-phospholipid antibody) were performed. In addition, screening of the maternal MTHFR C667T and MTHFR a 1298C mutation was determined by PCR.Result: all common serum test for study population (CMV, Toxo, Rubella, ACA and APL) IgG and IgM, also anticoagulants human blood test (protein C, protein S and Lupus) is negative. The frequency of heterozygous (genotype) A1298C and C677T was similar. The distribution of MTHFR, C677T and A1298C genotypes show significantly differences P ≤ 0.05; OR= (95%CI) between patients with multiple abortions and control subjects.Conclusions: the result suggestion MTHFR A>C 1298 and C< T 677 polymorphisms might be associated with multiple abortion in the examined population.

P251 Antiphospholipid antibodies in Crohn’s disease: Results of a prospective single-center study

Background Assess the prevalence of antiphospholipid antibodies (APL) and their association with disease phenotype and activity in patients with Crohn disease (CD). Methods This is a prospective study involving 30 patients with CD over a period of 2016 to 2020. Family and personal history of thromboembolic disease and fetal loss as well as their delay in relation to the date of the sample were taken from from the interrogation. Disease-related data such as age at the time of diagnosis, location and phenotype of the disease as well as treatment medical received were identified from the medical records. Disease activity was evaluated according to the CDAI (Crohn Disease Activity Index) score calculated time of inclusion. The serum of the patients was tested on anti-β2-glycoprotein-I (anti-β2-GPI Ig M / G), anti-cardiolipin (ACA Ig M / G) by method enzyme immunoassay (ELISA). This test was considered positive if the rate of anti-cardiolipin antibody was&gt; 12U / mL and the level of anti-β2- glycoprotein-1&gt; 8U / mL. The occurrence of thromboembolic events was noted during follow-up. Results The average age was 47.3 ± 10.8 years (29 men and 21 women). A family history of thromboembolic disease has been noted in 2 patients. A patient developed a pulmonary embolism 37 months before his inclusion in postoperative context. A history of fetal loss was reported in 7 women (16%) with a delay ranging from 5 to 432 months (in mean 181.6 ± 146) before their inclusion in the study. The average age at time of diagnosis was 37.9 ± 11.7 years. Colonic localization of the disease was noted in 12 patients (41.4%) and the inflammatory phenotype was the more common (62.1%). The disease was active in 13 patients (44.8%) with a mean CDAI score of 149.2 ± 111.7 (23–469). A patient has presented a mesenteric infarction during his follow-up 35 months after his inclusion. Positive anti-β2-glycoprotein-1 antibody levels IgG type with levels negative anti-cardiolipin antibodies were found in 2 patients (6%). No patient had positive anti-cardiolipin antibodies. No difference was found for the prevalence of anti-β2-GPI in patients patients in remission compared to those with active disease (p = 0.22) and in patients with severe acute colitis compared to the rest of the patients (p = 0.2). The frequency of β2-GP1 was not higher in patients with CRP greater than 6 mg / L compared to those with a normal CRP (p = 0.4). Anti-TNF treatment was started in 5 patients and no association was found between anti-TNF treatment and the prevalence of anti-β2-GP1 (p = 0.7). APL status was not associated with phenotype and localization of disease or thrombotic events. Conclusion The present study did not demonstrate an association between APL antibodies and disease phenotype or activity.

Risk Assessment and Antithrombotic Strategies in Antiphospholipid Antibody Carriers

Antiphospholipid antibodies (aPL) are a cluster of autoantibodies directed against plasma proteins with affinity for membrane phospholipids. The most frequently tested aPL are lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-β2GPI). aPL play a key pathogenic role in the development of the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by recurrent thrombotic and/or pregnancy complications in patients with persistent aPL. However, aPL positivity is occasionally documented in patients with no previous history of thrombotic or pregnancy morbidity. LA activity, multiple aPL positivity, high-titer aPL, and a concomitant systemic autoimmune disease are recognized risk factors for future thrombotic events in asymptomatic carriers. Moreover, an accelerated atherosclerosis with increased cardiovascular (CV) risk has also been associated with aPL positivity, thus exposing aPL carriers to fatal complications and chronic disability requiring cardiac rehabilitation. Overall, an accurate risk stratification is recommended for aPL-positive subjects in order to prevent both venous and arterial thrombotic complications. In this review, we provide an overview of the main antithrombotic and risk assessment strategies in aPL carriers.

AB0408 DOES THE PRESENCE IN THE SERUM OF ANTIPHOSPHOLIPID ANTIBODIES CORRELATE WITH SPECIFIC/NON SPECIFIC CAPILLAROSCOPIC ABNORMALITIES?

Background:Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by specific vascular and obstetric manifestations and by antiphospholipid antibodies (aPL) positivity [1].To date, little is known regarding nailfold videocapillaroscopy (NVC) alterations in APS patients and in asymptomatic aPL-carriers, non-specific abnormalities being the most frequently reported [2,3,4].Objectives:To retrospectively analyze NVC alterations in APS patients and in asymptomatic aPL-carriers and to correlate NCV alterations with both clinical manifestations and serum aPL profile.Methods:Thirty-five aPL positive patients having received at least one NCV investigation (mean age 47 years, range 16-81, 31 female and 4 male) were retrospectively included in the study. For each patient complete medical history was collected with a particular attention to past vascular thrombosis and pregnancy morbidity. Patients were classified as affected by APS according to the updated Sapporo classification criteria [5]. Lupus anticoagulant (LAC), IgM and IgG anti-cardiolipin antibodies (ACL) and IgM and IgG anti-Beta2 Glycoprotein 1 (anti-B2GP1) were assessed in each patient according to the recommended procedures [5]. NCV parameters were analyzed in each patient, with a particular interest to hemorrhages or nailfold bed-parallel hemosiderin deposits (“comb-like”hemorrhages) presence [2,6]. Statistical analysis was performed by parametric and non-parametric tests.Results:Seventeen patients (mean age 49 years, range 16-81 years) were asymptomatic aPL-carriers and 18 (mean age 46 years, range 26-71 years) were affected by APS. Within APS patients, 16 had a history of vascular thrombosis and 2 had pregnancy morbidity; in 6 patients APS was secondary to other autoimmune rheumatologic conditions (3 to Systemic Lupus Erythematosus, 2 to vasculitides and 1 to Mixed Connective Tissue Disease).Among the total number of aPL-carriers and APS patients six patients showed a normal NVC pattern, 24 patients had non-specific NVC abmormalities and 5 patients had a “scleroderma-like” pattern. Interestingly, NCV microhemorrhages were significantly more frequent in APS patients than in asymptomatic aPL-carriers, both in score and in absolute (p=0.05 andp=0.04, respectively). Particularly, in APS patients “comb-like”hemorrhages had a statistically significant higher prevalence than isolated hemorrhages (p=0.03). Dilated capillaries score was significantly higher in APS patients than in asymptomatic aPL-carriers (p=0.01).Not any statistically significant difference was observed regarding other capillary parameters (score of giant capillaries, loss of capillaries, or anormal shpaes, i.e. angiogenesis). Not any statistical correlation was observed between NVC parameters and different aPL profile.Conclusion:The study shows that the total number of microhemorrhages and in particular the“comb-like”subtype, are significantly the most frequent specific abnormalities in APL patients when compared to asymptomatic aPL carriers. The presence of the “scleroderma like” NVC pattern may suggest a concomitant overlap syndrome. Not any correlation was found between aPL profile and other NVC parameters. Further studies need to develop a more specific APS NVC pattern for APS patients.References:[1]Tektonidou MG, et al RMD Open 2019; 5(1);[2]Cutolo M, Elsevier 2010, pp141-143;[3]Candela M, et al.1998:444-9;[4]Aslanidis S, et al. Clin Exp Rheumatol 2011, 29:307-9;[5]Miyakis S, et al. J Thromb Haemost 2006, 4:295–306;[6]Cutolo M, et al Best Pract Res Clin Rheumatol 2008, 22:1093-108Disclosure of Interests: :Giorgia Ferrari: None declared, Sabrina Paolino: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carmen Pizzorni: None declared, Greta Pacini: None declared, Emanuele Gotelli: None declared, Adriano Lercara: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Antiphospholipid syndrome and challenges with direct oral anticoagulants

Direct oral anticoagulants have become the mainstay of the management of venous thromboembolism and atrial fibrillation, and long-term anticoagulation is indicated for those at high risk of further thrombotic events. This includes patients diagnosed with antiphospholipid syndrome, for whom the ‘triple positive’ laboratory combination of lupus anticoagulant, β2-glycoprotein-1 and anti-cardiolipin antibodies signify those at greatest risk. Data from meta-analysis and randomised control trials have raised the concern that direct oral anticoagulants may be less effective than vitamin K antagonists for the prevention of thrombosis in patients with thrombotic antiphospholipid syndrome, particularly those with the triple positive profile. This article reviews the diagnosis of thrombotic antiphospholipid syndrome, strategies for testing without interruption of anticoagulation, evidence concerning the safety of direct oral anticoagulants in this setting, and the implications for current investigation and management of unprovoked venous thromboembolism.

P172 Anti-domain I positivity in SLE at diagnosis is predictive of atherosclerotic plaque development

Background Cardiovascular disease is a significant burden on SLE patients, and no satisfactory markers exist to predict atherosclerotic development in patients. This study utilised an orthogonal approach to develop a marker of cardiovascular progression with predictive value in SLE patients. Methods The earliest available sample from a cohort of 92 SLE patients was tested for anti-Domain I (aDI), anti Beta-2-Glycoprotein-I, and anti-Cardiolipin antibodies. Persistent positivity was not assessed. These patients then had vascular ultrasound scans (carotid and femoral arteries) (mean 10 years later) to assess subclinical atherosclerotic plaque. A range of demographic, clinical and serological markers were recorded at the time of the scan. Predictors of plaque presence were investigated using binary logistic regression. Results A total of 34 patients from the cohort of 92 had atherosclerotic plaque (37%). A total of 32 patients had aDI positivity, of which 20 (62.5%) also had Plaque, this is reflected by the significantly higher levels of aDI antibodies seen in Plaque patients (p &lt; 0.01). Anti-DI positivity was predictive of the development of plaque in the future (Odds Ratio (OR) 5.476, p &lt; 0.001). No association was seen for any other antibody tested. Multiple binary logistic regression showed aDI positivity had as much predictive value as triglyceride levels on the day of the scan (OR 3.5 vs 3.9, Table 1) for predicting plaque in patients. Age at scan was a third independent variable associated with atherogenic plaque. Conclusion Early aDI positivity may be a good marker of atherogenesis in SLE patients in the long term. Disclosures T.C.R. McDonnell: Other; I am an inventor on the patent for Domain I. F. Farinha: None. C. Pericleous: Other; This Author is an Inventor on the Patent for Domain I. M. Griffin: None. A. Nicolaides: None. S. Croca: None. I. Giles: Other; This Author is an Inventor on the Domain I Patent. A. Rahman: Other; This Author is an Inventor on the Domain I Patent..