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Purpose of the Review Elevated levels of anti-phospholipid (aPL) antibodies are the most important criterion in the diagnosis of anti-phospholipid syndrome (APS) and are usually responsible for promoting the risk of thrombotic complications. Now, in the course of the global coronavirus disease 2019 (COVID-19) pandemic, measurable aPL antibodies have also been detected in a noticeable number of patients showing a variety ranging from studies with only isolated positive tests to cohorts with very high positivity. Thus, the question arises as to whether these two different clinical pictures may be linked. Recent Findings The ambivalent results showed a frequent occurrence of the investigated aPL antibodies in COVID-19 patients to an individually varying degree. While some question a substantial correlation according to their results, a number of studies raise questions about the significance of a correlation of aPL antibodies in COVID-19 patients. Within the scope of this review, these have now been described and compared with each other. Summary Ultimately, it is necessary to conduct further studies that specifically test aPL antibodies in a larger context in order to make subsequent important statements about the role of APS in COVID-19 and to further strengthen the significance of the described comparisons.

BACKGROUND AND PURPOSE The mechanism of glomerular microthrombosis (GMT) in patients with lupus nephritis (LN) is largely unknown. The aim of this study is to investigate the association between antiphospholipid antibodies (aPLs) and factor Bb in LN patients with GMT. METHODS Patients with biopsy-proven LN hospitalized from July 2015 to July 2018 in our hospital were selected for this study. Levels of lupus anticoagulant (LAC), anticardiolipin antibodies (aCLs), anti-β2-glycoprotein I (anti-β2-GPI) antibodies and factor Bb were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. RESULTS A total of 25 LN patients with GMT and 76 LN patients without GMT were included in this study. In LN patients with GMT, the presence of anti-β2GPI and LAC were both significantly higher than in those without GMT (P

​ObjectivesA single nucleotide polymorphism in the NCF1 gene (NCF1-339, rs201802880), encoding NADPH oxidase type II subunit NCF1/p47phox, reducing production of reactive oxygen species (ROS) is strongly associated with the development of systemic lupus erythematosus (SLE). This study aimed at characterising NCF1-339 effects on neutrophil extracellular trap (NET) formation, type I interferon activity and antibody profile in patients with SLE.​MethodsNeutrophil NET-release pathways (n=31), serum interferon (n=141) and finally antibody profiles (n=305) were investigated in SLE subjects from Lund, genotyped for NCF1-339. Then, 1087 SLE subjects from the rheumatology departments of four Swedish SLE centres, genotyped for NCF1-339, were clinically characterised to validate these findings.​ResultsCompared with patients with normal-ROS NCF1-339 genotypes, neutrophils from patients with SLE with low-ROS NCF1-339 genotypes displayed impaired NET formation (p​ConclusionsThe NCF1-339 SNP mediated decreased NADPH oxidase function, is associated with high interferon activity and impaired formation of NETs in SLE, allowing dependence on mitochondrial ROS. Unexpectedly, we revealed a striking connection between the ROS deficient NCF1-339 genotypes and the presence of phospholipid antibodies and APS.

Introduction Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. Objectives To determine whether epidemiological, clinical and immunological factors played a role in the long-term persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. Methods The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. Results Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-β2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82–0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0–0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03–7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. Conclusion Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

The objective of the study is to enhance sorption capacity of diagnostic agents by using cardiolipin antigens for antiphospholipid syndrome in patients with systemic lupus erythematosus (SLE). A technique of emulsion polimerization was used. 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. Following the method described above we performed sorption of anticardiolipin antibodies from blood plasma of SLE patients who showed clinical presentations of antiphospholipid syndrome. All SLE patoents with signs of antiphospholipid syndrome showed reliably higher levels of cardiolipin antibodies compared with SLE patients without antiphospholipid syndrome signs; the antibody level was 0.365 ± 0.026 and 0.075 ± 0.003 on average, correspondingly (p < 0.001). 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 ± 0.0289; after sorption 0.059 ± 0.0170; p

Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000–2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-β2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (–1.44 mL/min/year compared to –0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.

Objective To estimate the annual incidence and prevalence of and frequency of mortality associated with antiphospholipid syndrome (APS). Methods An inception cohort of patients with incident APS in 2000-2015 from a geographically well-defined population was identified based on comprehensive individual medical records review. All cases met the 2006 Sydney criteria for APS (primary definition) or had a diagnosis of APS confirmed by physician consensus (secondary definition). Levels of lupus anticoagulant, IgM and IgG anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies were tested in a centralized laboratory. Incidence rates were age- and sex-adjusted to the 2010 US white population. Prevalence estimates were obtained from the incidence rates, assuming that there was no increased mortality associated with APS and that migration in or out of the area was independent of disease status. Results Among this cohort in 2000-2015, 33 cases of incident APS, as defined by the Sydney criteria, were identified (mean age of patients 54.2 years; 55% female, 97% white). The annual incidence of APS in adults ages ≥18 years was 2.1 (95% confidence interval [95% CI] 1.4-2.8) per 100,000 population. Incidence rates were similar in both sexes. The estimated prevalence of APS was 50 (95% CI 42-58) per 100,000 population, and was similar in both sexes. Six patients (18%) had a concurrent diagnosis of systemic lupus erythematosus. The most frequent clinical manifestation was deep vein thrombosis. The overall frequency of mortality among patients with APS was not significantly different from that in the general population (standardized mortality ratio 1.61, 95% CI 0.74-3.05). Conclusion APS occurred in ~2 persons per 100,000 population per year. The estimated prevalence was 50 per 100,000 population. Overall mortality was not notably different from that observed in the general population.

Objective The objective of this study was to analyse autoantibodies’ titres modulation during belimumab treatment in 50 patients with systemic lupus erythematosus (SLE). Methods Sera were collected at belimumab start (T0) and every six months until the 24th month. Disease activity index (SLEDAI-2K) was analysed at every timepoint. High avidity anti-dsDNA was detected by radioimmunological method, anti-ENA, anti-cardiolipin antibodies (aCL), anti-β2 glycoprotein I (anti-β2GPI) were analysed by ELISA. Results Fifty patients with SLE (mean SLEDAI-2K: 7.18 ± :3), mean age of 39 ± 11 years and mean follow-up of 13 ± 7.8 years were enrolled. A significant decrease of anti-dsDNA and anti-β2GPI IgM titres was observed at all timepoints. IgG aCL titre showed significant decrease only at T18. Anti-dsDNA negativization was detected in 21%, anti-β2GPI IgG in 33% and aCL IgG in 30% of sera, mostly at T6. Anti-ribosomal showed a significant titre decrease at T6 and T12, with negative seroconversion at T18. Anti-Sm titre significantly dropped down at T6, then remained stable during the time. Significant correlations were found between anti-dsDNA and anti-ribosomal titre and between SLEDAI ratio (SLEDAI value/SLEDAI T0) and anti-ribosomal titre ratio (value/value T0). Conclusions Belimumab treatment induced a significant reduction of SLE-specific autoantibodies titre and IgM anti-β2GPI. Anti-ribosomal titre decrease correlates with anti-dsDNA titre and disease activity improvement.

Objectives aPL are present in between 20 and 30% of patients with SLE. They can cause vascular events (VE) or pregnancy morbidity. aCL and anti-beta-2-glycoprotein I (anti-β2GPI) are measured in clinical practice. Domain I (DI) of β2GPI is the main site for aPL binding. We investigated the prevalence of IgG anti-DI, aCL and anti-β2GPI antibodies in early SLE and their association with mortality and development of VE. Methods Samples from 501 patients with SLE that had been obtained and stored early during their disease were tested for IgG anti-DI, aCL and anti-β2GPI antibodies by ELISA. LA status and history of VE were obtained by reviewing medical records. Kaplan–Meier analysis was used to investigate mortality and occurrence of VE, comparing groups with and without aPL in early disease. Results Of 501 patients, 190 (38%) had at least one of these aPL, of whom 112 had anti-DI alone. Of 276 patients with complete vascular history, 83 had experienced VE. The 39 patients who were double or triple-ELISA-positive for any combination of the three aPL were more likely to have or develop lupus anticoagulant (P Conclusion IgG anti-DI antibodies were present in early serum samples from 29% of patients and were more common than IgG aCL or anti-β2GPI. There was some evidence suggesting that double or triple-ELISA-positivity for these antibodies identified a group with worse outcomes.

BACKGROUND Extractable nuclear antigen (ENA) and anti-double stranded DNA (anti-dsDNA) positivity and related diseases like systemic lupus erythematosus, Sjogren syndrome, and other autoimmune diseases are known to be associated with obstetrical complications and poor perinatal outcomes. OBJECTIVE To demonstrate the importance of ENA, anti-dsDNA, antiphospholipid (APL), and anticardiolipin (ACL) antibody positivity on pregnancy outcomes. METHODS Ninety one pregnant women with known ENA, anti-dsDNA, APL IgG and IgM, and ACL IgG and IgM antibody positivity were retrospectively compared with 91 randomly selected pregnant woman in terms of obstetrical complications and pregnancy outcomes. Beksac Obstetrics Index-pregnancy (BOIp), calculated as (number of children + (π/10))/gravidity in the current pregnancy, was used to compare the risk level between groups. RESULTS Significant differences were found in the median maternal age, gravidity, number of previous miscarriages, and BOIp between the groups (p= 0.04, p< 0.001, p< 0.001, and p< 0.001, respectively). Significant differences were also found between the study and control groups in the median gestational age at birth, birth weight, and APGAR1 score (p< 0.001 for all). Similarly, significant differences were found between groups in the rates of intra-uterine growth restriction, oligohydramnios, and gestational hypertension (p< 0.001, p= 0.05, and p= 0.05, respectively). There were 3 (3.3%) stillbirths in the study group and none in the control group (p= 0.123). CONCLUSION We evaluated the impact of anti-dsDNA, ENA, APL, and ACL antibody positivity, which may cause immunologic inflammation at placenta and thereby affect pregnancy outcomes.

The aim of this study was to evaluate how the cytokine profiles differed between autoantibody based subgroups of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disease, characterized by periods of flares (active disease) and remission (inactive disease). The disease can affect many organ systems, e.g., skin, joints, kidneys, heart, and the central nervous system (CNS). SLE patients often have an overproduction of cytokines, e.g., interferons, chemokines, and interleukins. The high cytokine levels are part of the systemic inflammation, which can lead to tissue injury. In the present study, SLE patients were divided into five groups based on their autoantibody profiles. We thus defined these five groups: ANA negative, antiphospholipid (aPL) positive, anti-Sm/anti-RNP positive, Sjögren's syndrome (SS) antigen A and B positive, and patients positive for more than one type of autoantibodies (other SLE). Cytokines were measured using Mesoscale Discovery (MSD) multiplex analysis. On the basis of the cytokine data, ANA negative patients were the most deviating subgroup, with lower levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-12/IL-23p40, and interferon gamma-induced protein (IP)-10. Despite low cytokine levels in the ANA negative group, autoantibody profiles did not discriminate between different cytokine patterns.

Background Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. Methods Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. Results In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-β2-glycoprotein I (β2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum β2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P

Objective: To define the role of IgA antibodies to cardiolipin (aCL) and IgA antibodies to beta-2 glycoprotein 1 (anti-β2-GP1) in the development of vascular complications in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Material and methods: A total of 187 patients with one of the following diagnoses: primary APS (PAPS), probable APS, SLE with APS, and SLE without APS. The comparison group consisted of 49 patients with other rheumatic diseases (RD), the control group included 100 relatively healthy individuals (without RD, oncological pathology, and infectious diseases). All patients underwent standard clinical, laboratory, and instrumental examinations before being included in the study and during follow-up. The aPL study included the determination of IgG/IgM aCL, IgG/IgM anti-β2-GP1 by enzyme-linked immunosorbent assay (ELISA), IgG/IgM/IgA aCL, IgG/IgM/IgA anti-β2-GP1 by chemiluminescence analysis (CLA), and lupus anticoagulant (LA). Results: IgA aCL were detected in 75 (40%) of the 187 patients with APS and SLE, in none of the comparison group, and in 2 (2%) of the control one. IgA anti-β2-GP1 were detected in 63 (34%) of the 187 patients with APS and SLE, in none of the patients in the comparison group, and in one (1%) of the control group. The prevalence of IgA aCL and IgA anti-β2-GP1 and their levels were statistically significantly higher in patients with APS (PAPS and SLE + APS) than the levels in patients with SLE and those of the comparison and control groups (p < 0.05). IgA aCL and IgA anti-β2-GP1 were significantly associated with thrombosis in APS (χ2 = 4.96; p = 0.02 and χ2 = 4.37; p = 0.04, respectively). The risk of thrombosis was 2.04 times higher in patients with positive IgA aCL than in patients without these antibodies, as well as in patients with positive IgA anti-β2-GP1; it was twice as high as in patients without antibodies. There was a high specificity of IgA aCL and IgA anti-β2-GP1 for both the diagnosis of APS and its clinical manifestations, despite a low sensitivity. Conclusions: The study revealed a relationship of thrombosis and APS with IgA aCL and IgA anti-β2-GP1. There was a high specificity of IgA aCL and IgA anti-β2-GP1 (95% and 93%, respectively) for the diagnosis of APS with a low sensitivity (54% and 44%, respectively). There were no patients with isolated positivity of IgA aCL and IgA anti-β2-GP1.

Background Coronavirus disease-2019 (COVID-19) is associated with thromboembolism. Antiphospholipid antibody (APLa) formation is one of the mechanisms. Vitamin D deficiency has been associated with thrombosis in antiphospholipid antibody syndrome. Objective Measure APLa and vitamin D in hospitalized COVID-19 patients with and without thrombosis to evaluate if thromboembolism is associated with concomitant APLa and vitamin D deficiency. Methods Case-control study. Hospitalized COVID-19 patients with a thromboembolic event (ischemic stroke, myocardial infarction, deep venous thrombosis/pulmonary embolism, Cases n = 20). Controls (n = 20): Age, sex-matched without thromboembolic events. Patients with autoimmune disorders, antiphospholipid antibody syndrome, thrombophilia, anticoagulation therapy, prior thromboembolism, chronic kidney disease 3b, 4, end-stage renal disease, and malignancy were excluded. Given the limited current literature on the role of concomitant antiphospholipid antibodies and vitamin D deficiency in causing venous and/or arterial thrombosis in hospitalized COVID-19 patients, we enrolled 20 patients in each arm. Anti-cardiolipin IgG/IgM, beta-2 glycoprotein-1 IgG/IgM, lupus anticoagulant and vitamin D levels were measured in both groups. Results Cases were 5.7 times more likely to be vitamin D deficient (OR:5.7, 95% CI:1.3–25.6) and 7.4 times more likely to have any one APLa (OR:7.4, 95% CI: 1.6–49.5) while accounting for the effects of sex. Patients with both APLa and vitamin D deficiency had significantly more thrombosis compared to patients who were antibody positive without vitamin D deficiency (100% vs 47.4%; p = 0.01). Conclusions Thrombosis in COVID-19 was associated with concomitant APLa and vitamin D deficiency. Future studies in COVID-19 should assess the role of vitamin D in reducing thrombosis.

Antiphospholipid antibodies (aPL) are related to poor pregnancy outcomes, but their effect on embryo implantation is unclear. We aimed to assess the prevalence of different aPL in women with recurrent implantation failure (RIF).We searched studies in PubMed (MEDLINE), Scopus and Cochrane Library. Quality of studies was scored by the Newcastle-Ottawa Scale and risk of bias assessment by items described in RevMan5 software. Statistical analyses were made using random-effects model and presented as pooled Odds Ratio (OR), 95% confidence interval (CI). Heterogeneity was assessed by IThis systematic review and meta-analysis included 17 studies and showed a high degree of variability in aPL positivity in RIF. In the latter, the risk of bias assessment suggested unclear bias on study performance with a median sample size and interquartile range for RIF patients and fertile women of 96 (57-417) and 100 (60.5-202.5), respectively. Among the criteria aPL, IgG anticardiolipin autoantibodies (OR 5.02, 95% CI [1.95, 12.93]) were associated with RIF. Within the non-criteria aPL, anti-β2 glycoprotein I-IgA (OR 64.8, 95% CI [9.74, 431.0]), and antiphosphatidylglycerol-IgG and IgM (OR 10.74, 95% CI [5.25, 22.0]; OR 4.26, 95% CI [1.76,10.31]; respectively) were associated with RIF, too.Anticardiolipin-IgG is a prevalent autoantibody in women with RIF. Three other non-criteria aPL, aβ2GP I-IgA, aPG-IgG and aPG-IgM also present a positive rate in RIF. Overall, these results advise about testing them as indicators of RIF risk in women seeking IVF treatment.

Acute transverse myelitis (TM) is a rare complication secondary to systemic lupus erythematosus (SLE) that can cause patients' extensive and severe neuropsychiatric disorders. Due to the rarity of the onset of acute TM, there is still no standard treatment protocol. This study was to summarize the clinical features of SLE-TM through a case report and systematic review.We report a case of acute TM with the initial symptoms of headache and fever on admission to hospital, with lesions in medulla oblongata, cervical medulla, and thoracic medulla. Furthermore, all cases of SLE combined with acute TM from January 1975 to February 2022 were concluded and reviewed to compare the disease's current treatment strategies and prognosis.Patients with SLE-TM are mainly female (97.65%), with an average age of 36.89, a TM incidence of 24.51% and a longitudinal myelitis (LM) incidence of 67.76%. In addition, 68.63% of patients present an increased albumin, and only 16.50% of patients could recover. 32.35% of patients showed positive anti-cardiolipin antibody. Moreover, the patients who could recover are generally younger than those in the improved and paraparesis groups. After classifying the statistical results twice according to magnetic resonance imaging results and prognosis respectively, the erythrocyte sedimentation rate (ESR) in LM group was significantly higher than that in the other two groups. The positive rate of anti-DNA and anti-cardiolipin antibody (ANCL) in TM group was significantly higher than that of the other groups. According to the prognostic grouping, ESR in the recovery group was significantly higher than those in the other two groups. The positive ANCL in the poor prognosis group was slightly higher than that in the other two groups.We offer a novel insight for this rare disease and hope to bring some inspiration the basic research for SLE-TM.

To validate the association of thrombotic events with positive lupus anticoagulant (LA) and co-presence of anti-RNP/Sm, as well as the diagnostic accuracy of this combination of antibodies for thrombosis. Case-control study of patients with systemic lupus erythematosus (SLE) who presented thrombosis after SLE diagnosis and controls with SLE without thrombosis. Comorbidities, traditional risk factors, clinical variables, and treatment were evaluated. Antiphospholipid (aPL) and anti-RNP/Sm antibodies were determined. Sixty-three cases and 63 controls were studied, 88% women, median age of 40 years, and disease duration of 135 months at study inclusion. No differences were found between groups regarding age, comorbidities, or clinical characteristics at SLE diagnosis. Patients with thrombosis were more frequently positive for anti-RNP/Sm (p = 0.001), IgG aCL (p = 0.02), IgG anti-B2GPI (p = 0.02), IgM anti-B2GPI (p = 0.02), LA (p

International audience; Purpose of review: COVID-19 patients have a procoagulant state with a high prevalence of thrombotic events. The hypothesis of an involvement of antiphospholipid antibodies (aPL) has been suggested by several reports. Here, we reviewed 48 studies investigating aPL in COVID-19 patients.Recent findings: Prevalence of Lupus Anticoagulant (LA) ranged from 35% to 92% in ICU patients. Anti-cardiolipin (aCL) IgG and IgM were found in up to 52% and up to 40% of patients respectively. Anti-β2-glycoprotein I (aβ2-GPI) IgG and IgM were found in up to 39% and up to 34% of patients respectively. Between 1% and 12% of patients had a triple positive aPL profile. There was a high prevalence of aβ2-GPI and aCL IgA isotype. Two cohort studies found few persistent LA but more persistent solid phase assay aPL over time. aPL determination and their potential role is a real challenge for the treatment of this disease.

Objectives: The present meta-analysis aimed to assess the relationship between antiphospholipid antibodies (aPLs) or antiphospholipid antibody syndrome (APS) and the incidence of osteonecrosis (ON)...

Portal venous system thrombosis (PVST), a common complication of liver cirrhosis, is closely associated with thrombophilia. To explore the association of homocysteine (Hcy), anticardiolipin antibody (aCL), and anti-β2 glycoprotein I antibody (aβ2GPI), which are possible thrombophilic factors, with PVST in liver cirrhosis. Overall, 654 non-malignant patients (219 with and 435 without liver cirrhosis) admitted between January 2016 and June 2020 were retrospectively evaluated. Presence of PVST, degree of main portal vein (MPV) thrombosis, and clinically significant PVST were identified. Hcy level, hyperhomocysteinemia (HHcy), aCL positivity, and aβ2GPI positivity were compared according to the presence of liver cirrhosis and PVST. Positive aβ2GPI was significantly more frequent in patients with liver cirrhosis than those without, but Hcy level and proportions of HHcy and positive aCL were not significantly different between them. PVST could be evaluated in 136 cirrhotic patients. Hcy level [10.57 μmol/L (2.71-56.82) versus 9.97 μmol/L (2.05-53.44); P = 0.796] and proportions of HHcy [4/44 (9.1%) versus 13/81 (16.0%); P = 0.413] and positive aCL [1/23 (4.3%) versus 10/52 (19.2%); P = 0.185] and aβ2GPI [9/23 (39.1%) versus 21/52 (40.4%); P = 0.919] were not significantly different between cirrhotic patients with and without PVST. There was still no significant association of Hcy level, HHcy, aCL, or aβ2GPI with PVST based on Child-Pugh classification, MPV thrombosis >50%, and clinically significant PVST. Hcy, aCL, and aβ2GPI may not be associated with PVST in liver cirrhosis, suggesting that routine screening for Hcy, aCL, and aβ2GPI should be unnecessary in such patients.

Objectives This study aimed to investigate the association of antiphospholipid antibodies (aPL) with clinical activity and renal pathological activity in patients with lupus nephritis (LN). Methods Levels of anticardiolipin () antibodies, anti-β2-glycoprotein I (anti-β2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. Results A total of 83 patients with LN were included in this study, 40 patients (48.2%) in the s positive group and 43 patients in the aPL negative group. LN patients with positive aPL had significantly higher SLEDAI (p = 0.012), more hematuria (p = 0.043), lower serum C3 (p = 0.003) and C4 (p = 0.014), and a higher pathological activity index (p = 0.012), more micro-thrombosis (p = 0.046) and more C3 deposits (p = 0.038) in the glomerulus than patients with negative aPL The level of IgG- was significantly correlated with SLEDAI and serum level of C3 (r = 0.44, p Conclusions Our work suggests that aPL, especially, are correlated with both clinical activity and renal pathological activity in patients with LN.

Background Antiphospholipid syndrome (APS) is an acquired pre-thrombotic autoimmune condition, which produces autoantibodies called antiphospholipid antibodies (APL) against phospholipid-binding plasma proteins. The diagnosis of APS requires at least one of Sapporo standard clinical manifestations and one laboratory criteria (persistently medium/high titer anticardiolipin antibodies, and/or medium/high titer anti-β2-glycoprotein I antibodies, and/or a positive lupus anticoagulant test). Gastrointestinal lesions are rarely reported in APS patients. APS cases with recurrent abdominal pain as the first clinical manifestation are even rarer. Case presentation This report describes an APS case with recurrent abdominal pain as the first clinical manifestation of antiphospholipid syndrome. The patient has a history of two miscarriages. Computed tomography of the abdomen confirmed mesenteric thrombosis and intestinal obstruction while laboratory tests for serum antiphospholipid and anti-β2-glycoprotein I antibodies were positive. This led to the diagnosis of APS. Conclusions This paper provides useful information on gastrointestinal manifestations and APS, also including a brief literature review about possible gastrointestinal symptoms of APS.

BACKGROUND The relationship between anticardiolipin (aCL) antibodies and cardiovascular events is uncertain and may vary according to arterial location. MATERIALS AND METHODS FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral artery disease (PAD). The rate of subsequent ischaemic events was cross-referenced with the presence of aCL antibodies (any isotype, IgG or IgM). RESULTS As of June 2017, 1387 stable outpatients were recruited. Of these, 120 (8.7%) showed positive levels of aCL antibodies. Over an average follow-up of 18 months, 250 patients developed subsequent events: 101 myocardial infarction, 57 ischaemic stroke and 92 critical leg events. Patients with positive aCL antibodies had a higher risk of distal artery events (a composite of ischaemic stroke or critical leg events) than patients with undetectable or low levels (rate ratio: 1.66; 95% CI: 1.07-2.60). However, an association with central coronary events was not found. The multivariate Cox analysis after adjustment for relevant clinical covariates showed that positivity of aCL antibodies is an independent risk factor for distal events (hazard ratio: 1.60; 95% CI: 1.01-2.55; P

Purpose: Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (−) subgroups of GO patients. Methods: Study included consecutive patients with GO (66 with Graves’ (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. Results: aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). Conclusion: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced against a variety of phospholipids and phospholipid-binding proteins. The purpose of this article is to review cutaneous findings in patients with APS diagnosis. An overview regarding prevalence, description, pathogenesis and histopathology, are described for cutaneous manifestations of APS.

Antiphospholipid antibody syndrome (APS) is characterized by the development of venous and/or arterial thrombosis and by gestational morbidity (recurrent fetal losses) in the presence of antiphospholipid antibodies. We report the case of a 38-year-old woman who was diagnosed with primary APS from thromboembolic abnormalities in the retinal periphery that led to retinal ischemia. The aim of this study is to share with physicians and medical undergraduates an atypical manifestation of the syndrome that is the most common acquired thrombophilia, that should be part of the diagnostic routine of all clinical specialties. RESUMO A síndrome do anticorpo antifosfolipídio (SAAF) caracteriza-se pelo desenvolvimento de tromboses venosas e/ou arteriais e pela morbidade gestacional (perdas fetais recorrentes) na presença de anticorpos antifosfolipídicos. Foi relatado o caso de uma paciente de 38 anos que foi diagnosticada com SAAF primária, a partir de alterações tromboembólicas na periferia da retina, que levaram à isquemia retiniana. O objetivo desse estudo é compartilhar com médicos e acadêmicos de medicina uma manifestação atípica da síndrome que é a trombofilia adquirida mais comum, devendo fazer parte da rotina diagnóstica de todas as especialidades clínicas.

Background Anti beta 2glycoprotein I (a beta 2GPI) and anticardiolipin (aCL) IgG/IgM show differences in positive/negative agreement and titers between solid phase platforms. Method-specific semiquantitative categorization of titers could improve and harmonize the interpretation across platforms. Aim To evaluate the traditional 40/80-unit thresholds used for aCL and a beta 2GPI for categorization into moderate/high positivity with different analytical systems, and to compare with alternative thresholds. Material and methods aCL and a beta 2GPI thresholds were calculated for two automated systems (chemiluminescent immunoassay [CLIA] and multiplex flow immunoassay [MFI]) by receiver operating characteristic curve analysis on 1108 patient samples, including patients with and without antiphospholipid syndrome (APS), and confirmed on a second population (n = 279). Alternatively, regression analysis on diluted standard material was applied to identify thresholds. Thresholds were compared to 40/80 threshold measured by an enzyme-linked immunosorbent assay (ELISA). Additionally, likelihood ratios (LR) were calculated. Results Threshold levels of 40/80 units show poor agreement between ELISA and automated platforms for classification into low/moderate/high positivity, especially for aCL/a beta 2GPI IgG. Agreement for semiquantitative interpretation of antiphospholipid antibodies (aPL) IgG between ELISA and CLIA/MFI improves with alternative thresholds. LR for aPL IgG increase for thrombotic and obstetric APS based on 40/80 thresholds for ELISA and adapted thresholds for the other systems, but not for IgM. Conclusion Use of 40/80 units as medium/high thresholds is acceptable for aCL/a beta 2GPI IgG ELISA, but not for CLIA and MFI. Alternative semiquantitative thresholds for non-ELISA platforms can be determined by a clinical approach or by using monoclonal antibodies. Semiquantitative reporting of aPL IgM has less impact on increasing probability for APS.

Anti‐phospholipid syndrome (APS) is a systemic autoimmune disorder defined by the simultaneous presence of vascular clinical events, pregnancy morbidity and anti‐phospholipid antibodies (aPL). In clinical practice, it is possible to find patients with APS who are persistently negative for the routine aPL tests (seronegative APS; SN‐APS). Recently, the identification of aPL immunoglobulin (Ig)A and/or anti‐β2‐glycoprotein‐I (β2‐GPI) IgA was shown to represent a further test in SN‐APS patients. In this study we analyzed the presence of anti‐vimentin/cardiolipin (aVim/CL) IgA in a large cohort of patients with SN‐APS, evaluating their possible association with clinical manifestations of the syndrome. This study includes 60 consecutive SN‐APS patients, 30 patients with APS and 40 healthy donors. aVim/CL IgA were detected by enzyme‐linked immunosorbent assay (ELISA). Results show that 12 of 30 APS patients (40%) and 16 of 60 SN‐APS patients (26.7%) resulted positive for aVim/CL IgA. Interestingly, SN‐APS patients who tested positive for aVim/CL IgA showed a higher prevalence of arterial thrombosis (p = 0.017, likelihood positive ratio = 5.7). This study demonstrates for the first time, to our knowledge, the presence of aVim/CL IgA in sera of patients with APS. In particular, they revealed a potential usefulness in identification of a significant proportion of SN‐APS patients. Moreover, as patients tested positive for aVim/CL IgA reported a high likelihood ratio to have the clinical features of APS, this test may be considered a suitable approach in the clinical evaluation of SN‐APS., This study demonstrates the presence of aVim/CL IgA in patients with APS. They revealed potential usefulness in the identification of a significant proportion of ‘seronegative’ APS patients (SN‐APS). Patients tested positive for aVim/CL IgA showed a higher prevalence of arterial thrombosis, suggesting that this test may be considered a suitable approach in the evaluation of SN‐APS patients.

BACKGROUND The diagnosis of antiphospholipid syndrome (APS) relies predominantly on the laboratory measurement of antiphospholipid antibodies (aPLs). We attempt to verify the analytical performance of anticardiolipin antibodies (aCL) IgA/IgG/IgM and anti-β2-glycoprotein I antibodies (aβ2GPI) IgA/IgG/IgM on a high-throughput automated immunoassay platform. METHODS Limit of blank (LOB), limit of detection (LOD), imprecision, and linearity were calculated according to the corresponding Clinical and Laboratory Standards Institute (CLSI) guidelines protocols. The biological reference intervals (RIs) were verified in healthy individuals. RESULTS The LoB of aCL IgA/IgG/IgM and aβ2GPI IgA/IgG/IgM were 0.000, 1.200, 0.200, and 0.400, 1.250, 0.100, respectively. The LoD were 0.093, 1.715, 0.337 and 0.547, 2.174, 0.185 CU, respectively. All the within-run CVs and total CVs were less than the criterion at 10%. The linear analysis showed a good correlation between the predictive values and observed values with correlation coefficients greater than 0.99. CONCLUSIONS The BIO-FLASH automated chemiluminescent analyzer performed well in measuring aPLs.

The purpose of our study was to evaluate pregnancy outcomes of women with antiphospholipid antibodies (aPL) positivity and assess risk factors associated with adverse pregnancy outcomes. Pregnant women with aPL positivity were enrolled prospectively in China from January 2017 to March 2020. Treatment of low-dose aspirin and low molecular weight heparin were given. Pregnancy outcomes and coagulation function were recorded and compared with normal pregnancies. Multivariable logistic regression was performed to identify risk factors associated to intrauterine growth restriction (IUGR). 270 pregnant women, including 44 diagnosed as Antiphospholipid syndrome (APS), 91 as non-criteria APS (NCAPS) and 135 normal cases as control, were enrolled in the study. The live birth rate in aPL carriers and APS group was 97% and 95.5%, respectively. Adverse pregnancy outcomes did not show significant difference between aPL carriers and normal pregnancies, and between APS and NCAPS, except for IUGR. The incidence of IUGR was significantly higher in aPL carriers than normal pregnancies, and in APS patients than NCAPS (P < 0.05). After controlling for age, in vitro fertilization (IVF), pregnancy losses related to APS and treatment, anticardiolipin (aCL) positivity was the only variable significantly associated with IUGR, with an adjusted odds ratio of 4.601 (95% CI, 1.205-17.573). Better pregnant outcomes of aPL positive women, include APS and NCAPS, were achieved in our study with treatment based on low-dose aspirin (LDA) plus low molecular weight heparin (LMWH). The incidence of IUGR was still higher in them, and aCL positivity was the only one risk factor associated with IUGR.

SUMMARY The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these “criteria” of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies. RESUMO A classificação de Sapporo revisada para a síndrome antifosfolipídica definida de 2006 incluiu como critérios laboratoriais aqueles testes para anticorpos antifosfolípides cuja acurácia era considerada satisfatória de acordo com a evidência então disponível. Porém, na prática, a sensibilidade e especificidade desses anticorpos antifosfolípides “critério” são por vezes insuficientes para identificar ou descartar a síndrome antifosfolípide. Tem-se estudado se a acurácia do diagnóstico laboratorial da síndrome poderia ser melhorada por meio da testagem de anticorpos antifosfolípides não critério. Neste trabalho revisamos a evidência a respeito das associações clínicas e valor diagnóstico dos anticorpos não critério mais estudados, nomeadamente: anticorpos antifosfatidiletanolamina, antianexina A5, antiprotrombina, anticomplexo fosfatidilserina/protrombina, IgA anticardiolipina e IgG antidomínio I da anti-β2 glicoproteína I.

Background/PurposeLoss of positivity of antiphospholipid antibodies has been observed in clinical practice post-thrombosis in patients with SLE with secondary antiphospholipid syndrome (APS). Our study defined the frequency of this loss and the duration before positivity recurred.MethodsIn this prospective study, patients with SLE having at least two positive antiphospholipid markers prior to thrombosis and at least 1 year of follow-up after thrombosis were included. Antiphospholipid markers included lupus anticoagulant (dilute Russell viper venom test >45 s followed by mixing and confirmatory tests) and/or anticardiolipin titre (aCL IgG ≥20, aCL IgM ≥20 and/or aCL IgA ≥20). The percentage of visits with positive antiphospholipid markers after thrombosis was calculated. For patients with a negative antiphospholipid marker any time after thrombosis, survival estimates were performed to calculate the time to return of antiphospholipid positivity.ResultsIn APS due to SLE, complete loss of antiphospholipid positivity post-thrombosis was up to 41% for aCL IgG, 51% for IgM and 50% for IgA, but only 20% for those with lupus anticoagulant. Of those who at some point lost aCL IgG or became negative for lupus anticoagulant, the majority (60% and 76%, respectively) reacquired the antibody within 5 years. In contrast, of those who lost aCL IgM or IgA, fewer reacquired it within 5 years (37% and 17%, respectively).ConclusionIntermittent positivity of antiphospholipid antibodies is present in APS due to SLE. These fluctuations make it difficult to decide on length of anticoagulation. Lupus anticoagulant is more likely to persist post-thrombosis.