Role Of Antiphospholipid Antibodies Research Articles

Antibodies to Domain I β2-Glycoprotein 1 in Patients with Antiphospholipid Syndrome and Systemic Lupus Erythematosus

The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of β2-glycoprotein 1 (β2-GP1), IgG anti-β2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-β2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-β2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-β2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-β2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-β2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-β2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-β2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-β2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-β2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-β2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-β2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively).

Role of antiphospholipid antibodies in Covid-19 and its correlation with disease progression

Abstract Background The SARS-CoV2 infection that leads to COVID-19 is a condition with an erratic and changeable course. The majority of patients have the mildest form, which frequently has flu-like symptoms so mild that the illness can go unnoticed. Acute respiratory distress syndrome (ARDS), progressive hypoxemia, and unilateral or bilateral pneumonia are among the severe manifestations that occur in about 15% of infected patients and may necessitate mechanical ventilation support. When systemic hyperinflammation is in its worst, multiple organs are affected (cytokine storm), lymphopenia is present, and levels of ferritin, D-dimers, C-reactive protein, chemokines and cytokines, are markedly elevated. Aim of the work To research the association between COVID-19 patient antiphospholipid (APL) markers and thrombotic events. Patients and methodology Our study was a cross-sectional study and patients were selected from ward and ICU unit in Dar El Shefa Hospital, Cairo governorate. Results Our study demonstrated that cases with risk factors for thromboembolic events had worse outcomes more frequently; obesity was a statistically significant factor in these differences. Additionally, we discovered that cases with cytokine storm had worse outcomes more frequently, and that the differences in thromboembolic events and deep venous thrombosis were statistically significant. Conclusion In COVID-19 pneumonia patients, the clinical significance of antiphospholipid syndrome (APAs) is still unknown. Furthermore, it is still unclear how long these APAs last and how much they contribute to thrombotic events in patients.

Evaluation of the association between antiphospholipid antibodies and ICU admission outcome in critically ill COVID-19 patients in Iranian population

The role of anti-phospholipid antibodies (aPLs) in the prognosis of COVID-19 patients is controversial. In order to prove the role of this factor, the necessary measures such as early initiation of anticoagulants should be started even in the early stages of the disease and in outpatients or the use of other drugs in addition to anticoagulants. We decided to investigate the role of these antibodies in ICU admission outcomes in critically ill COVID-19 patients. The case-control study was carried out in Isfahan, Iran, from March to September 2021. One hundred nine patients in the case group were selected, including patients admitted to the ICU with a COVID-19 diagnosis. The 140 patients in the control group were selected from hospitalized and outpatients with COVID-19 with PCR + and pulmonary involvement, similar to the case group without the need for ICU hospitalization. The anti B2GP1 (IgM, IgG) and anti-cardiolipin (IgM, IgG)) were compared in two groups. The frequency percentage of patients in the abnormal group of anti-phospholipid antibodies was about 10% in total. No statistically significant difference in these aPLs in continued measures was observed between the two groups of patients admitted to the ICU and those outside the ICU. Also, in the logistics regression analysis, no significant association was observed. Therefore, the cause of coagulation in patients admitted to the ICU is not related to these aPLs. This means that aPLs could not be a good predictor of patient admission to the ICU.

Prothrombotic role of antiphospholipid antibodies in a patient with sickle cell disease

&lt;abstract&gt; &lt;p&gt;Sickle cell disease (SCD) is a common inherited condition in African, Caribbean, and Mediterranean countries. SCD is a hematologic disorder caused by a well-characterized point mutation in the β-globin gene, which produces an abnormal hemoglobin S that results in the sickling of red blood cells in deoxygenated conditions. Patients with SCD display a “hypercoagulation state” leading to an increased risk of severe venous and arterial thrombotic vascular events. Herein we report a case of severe thrombotic complications in a patient with SCD who showed high antiphospholipid antibodies (APA) levels during vascular occlusions.&lt;/p&gt; &lt;/abstract&gt;

Extra criterial antiphospholipid antibodies in patients with antiphospholipid syndrome and systemic lupus erythematosus (preliminary data)

The role of antiphospholipid antibodies (aPL), which are not included in the classification criteria, in antiphospholipid syndrome (APS) andsystemic lupus erythematosus (SLE) is not well understood.Objective: to determine the frequency of detection of IgG antibodies to domain 1 of β2-glycoprotein 1 (IgG-aβ2GP1-D1), IgA antibodiesto cardiolipin (aCL) and IgA antibodies to β2-glycoprotein 1 (IgA-a β2GP1) in patients with primary APS and APS in combination withSLE.Patients and methods. The study included 63 patients in whom IgG/IgM-aCL and IgG/IgM-aβ2GP1 were detected by enzyme-linkedimmunosorbent assay (ELISA) and IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GP1 and IgG-aβ2GP1-D1 by chemiluminescence analysis (CLA).Results and discussion. The detection rate of IgG-aβ2GP1-D1 was 76%, IgA-aCL – 56%, IgA-aβ2GP1 – 48%. Isolated positivity for IgA-aCL,IgA-aβ2GP1, IgG-aβ2GP1-D1 was not observed. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with high positivity forIgG/IgM-aCL and IgG/IgM-aβ2GP1. There was a statistically significant relationship between IgA-aCL/IgA-aβ2GP1 and the standard aPLprofile, as well as IgG-aβ2GP1-D1, IgG-aCL and IgG-aβ2GP1.Conclusion. A high detection rate of IgG-aβ2GP1-D1, IgA-aCL, IgA-aβ2GP1 was found in patients with APS. A statistically significant relationshipwas found between IgA-aCL/IgA-aβ2GP1 and the standard aPL profile, as well as IgG-aβ2GP1-D1 with IgG-aCL and IgG-aβ2GP1.

Prevalence of heart failure with preserved ejection fraction in antiphospholipid antibodies syndrome. The multicenter ATHERO-APS study

Abstract Background The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. Methods Prospective multicenter cohort study including 125 patients: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP &amp;gt;220 pg/ml, left atrial (LA) enlargement, increased left ventricular filling pressure. Results Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE (Figure). Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG &amp;gt;40 GPL (odds ratio [OR] 3.43, 95% Confidence Interval [CI] 1.09–10.77, p=0.035), anti β-2-glycoprotein-I IgG &amp;gt;40 GPL (OR 5.28, 1.53–18.27, p=0.009), lupus anticoagulants DRVVT &amp;gt;1.25 (OR 5.20, 95% CI 1.10–24.68, p=0.038), (OR 3.56, 95% CI 1.11–11.47, p=0.033) and triple positivity (OR 3.56, 95% CI 1.11–11.47, p=0.033) were associated with HFpEF after adjustment for age and sex. Discussion HFpEF has a clinically relevant prevalence in patients with APS. The role of antiphospholipid antibodies in the pathogenesis and prognosis of HFpEF needs to be investigated. Funding Acknowledgement Type of funding sources: None.

Long-Term Evaluation of Antiphospholipid Antibodies in Patients with COVID-19

Background: The role of antiphospholipid antibodies (aPL) in COVID-19 coagulopathy remains controversial; moreover, follow-up data after >12 weeks are lacking.Methods: In this prospective single-centre study, we determined ‘criteria’ (IgG, IgM) and ‘non-criteria’ (IgA) anti–β2-glycoprotein I (anti-β2-GPI), and anti-cardiolipin (aCL) antibodies, as well as lupus anticoagulant (LAC) in 157 consecutive adult inpatients with COVID-19. Repeat testing was offered after >12 weeks to all patients with initially positive results.Findings: Patients had a median age of 69 years, and 38·9% were admitted to the intensive care unit (ICU). LAC was present in 35·6%, aCL in 12·5%, and anti-β2-GPI in 15·6% of the patients, respectively. The most commonly detected isotype was IgA (17·1%), followed by IgM (5·9%), and IgG (2·6%). Occurrence of LAC and/or aPL was observed in 73 (48·7%) patients and was associated with ICU treatment and higher C-reactive protein (p=0·009, and p=0·019 respectively), but not with thromboembolic events (p=0·130) when compared to the aPL-negative population. Patients with IgA double-positivity showed an increased 30-days mortality (75·0% vs 95·1%; p=0·001). Of the 73 patients with positivity for LAC and/or aPL, 38 (52·1%) patients were available for follow-up after >12 weeks. The median LAC ratio decreased from 1·30 (1·22-1·37) at first timepoint to 1·15 (1·10-1·25) (p=0·001) at follow-up, while aPL positivity remained unchanged.Interpretation: aPL are a transient phenomenon in COVID-19 most likely related to ‘non-criteria’ antibodies and inflammation and are associated with disease severity, but not with macrothrombotic events. Patients with double positivity for IgA aPL have an inferior survival probability.Funding Statement: Laboratory testing was supported in parts by Axonlab and Thermo Fisher Scientific.Declaration of Interests: Dr. Gerber reports non-financial support and funding for accredited continuing medical education program from Axonlab, and from Thermo Fisher Scientific, during the conduct of the study; personal fees and funding for accredited continuing medical education program from Alnylam, grants, personal fees and funding for accredited continuing medical education program from Pfizer, funding for accredited continuing medical education program from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma, SOBI, Janssen, Novo Nordisk, Mitsubishi Tanabe Pharma, outside the submitted work; Dr. Rossi reports unrestricted research grant, consultancy, travel from Jannsen, Abbvie, and AstraZeneca, outside the submitted work; Dr. Bernasconis institution received fees for his participation to advisory boards, travel grants from Gilead Sciences, ViiV Healthcare, Merck Sharp and Dohme, Pfizer, Abbvie, Sandoz AG, outside the submitted work; All other authors have nothing to disclose.Ethics Approval Statement: Clinical data were extracted from the electronic medical records. The study was approved by the Ethical Committee Ticino, Switzerland (2020-00838 RIF.CE 3621), and the need for a written informed consent was waived due to the non-interventional design of the trial with use of pre-existing biological material and health care data.

Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome

The diagnosis of antiphospholipid syndrome (APS) relies on the detection of antiphospholipid antibodies (aPL). Currently, lupus anticoagulant (LA), anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory criteria, if persistently present. LAC measurement remains a complicated procedure with many pitfalls and interfered by anticoagulant therapy. Solid-phase assays for aCL and aβ2GPI show interassay differences. These methodological issues make the laboratory diagnosis of APS challenging. In the interpretation of aPL results, antibody profiles help in identifying patients at risk. Other aPL, such as antibodies against the domain I of beta2-glycoprotein (aDI) and antiphosphatidylserine-prothrombin (aPS/PT) antibodies have been studied in the last years and may be useful in risk stratification of APS patients. Because of the methodological shortcomings of immunological and clotting assays, these non-criteria aPL may be useful in patients with incomplete antibody profiles to confirm or exclude the increased risk profile. This manuscript will focus on the laboratory aspects, the clinical relevance of assays and interpretation of aPL results in the diagnosis of APS.

Antiphospholipid syndrome in a pregnant woman and global cerebral ischemia in a newborn: are they connected?

Cerebral ischemia is the most common pathology of the central nervous system in newborns, and its neuropsychological consequences cause child disability. The global cerebral ischemia in a newborn may be caused by a violation of fetoplacental blood flow in pregnant woman with antiphospholipid syndrome. The article considers the role of antiphospholipid antibodies in the pathogenesis of hypoxice-mia-ischemic brain damage of the fetus and newborn child. The authors present a clinical case of a patient with spastic cerebral palsy and delayed psychomotor development born from a mother with antiphospholipid syndrome.

Pediatric Motor Inflammatory Neuropathy: The Role of Antiphospholipid Antibodies

We report the clinical case of a nine-year-old girl who presented with progressive motor neuropathy, revealed via the detection of a higher delay in F-wave recording using digitalized nerve conduction/electromyography. Since the lupus anticoagulant (LAC) positivity, detected using diluted Russell viper venom time (dRVVT), switched to persistent serological anticardiolipin immunoglobulin G (IgG) positivity, a possible non-thrombotic antiphospholipid antibody (aPL)-related clinical manifestation was suspected, and intravenous immunoglobulin treatment (IVIG) was started. The IVIG treatment was well tolerated and the complete resolution of motor impairment was obtained after the third IVIG infusion. Our findings suggest that it could be useful to check for antiphospholipid antibodies in children with a rapid onset of progressive neurological signs in order to provide the beneficial use of IVIG in the treatment of pediatric aPL neurological conditions.

Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies

ObjectiveThe role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities.MethodsHealthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females.ResultsPregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-β2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-β2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased.ConclusionsIgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.

The Role of Antiphospholipid Antibodies in Pathogenesis of Myocardial Infarction in Young Adults

The Role of Antiphospholipid Antibodies in Pathogenesis of Myocardial Infarction in Young Adults

Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac-1.

While the role of antiphospholipid antibodies in activating endothelial cells has been extensively studied, the impact of these antibodies on the adhesive potential of leukocytes has received less attention. This study was undertaken to investigate the extent to which antiphospholipid syndrome (APS) neutrophils adhere to resting endothelial cells under physiologic flow conditions and the surface molecules required for that adhesion. Patients with primary APS (n = 43), patients with a history of venous thrombosis but negative test results for antiphospholipid antibodies (n = 11), and healthy controls (n = 38) were studied. Cells were introduced into a flow chamber and perfused across resting human umbilical vein endothelial cells (HUVECs). Surface adhesion molecules were quantified by flow cytometry. Neutrophil extracellular trap release (NETosis) was assessed in neutrophil-HUVEC cocultures. Upon perfusion of anticoagulated blood through the flow chamber, APS neutrophils demonstrated increased adhesion as compared to control neutrophils under conditions representative of either venous (n = 8; P < 0.05) or arterial (n = 15; P < 0.0001) flow. At the same time, APS neutrophils were characterized by up-regulation of CD64, CEACAM1, β2 -glycoprotein I, and activated Mac-1 on their surface (n = 12-18; P < 0.05 for all markers). Exposing control neutrophils to APS plasma or APS IgG resulted in increased neutrophil adhesion (n = 10-11; P < 0.0001) and surface marker up-regulation as compared to controls. A monoclonal antibody specific for activated Mac-1 reduced the adhesion of APS neutrophils in the flow-chamber assay (P < 0.01). The same monoclonal antibody reduced NETosis in neutrophil-HUVEC cocultures (P < 0.01). APS neutrophils demonstrate increased adhesive potential, which is dependent upon the activated form of Mac-1. In patients, this could lower the threshold for neutrophil-endothelium interactions, NETosis, and possibly thrombotic events.

Damage index in lupus: the role of antiphospholipid antibodies.

Damage index in lupus: the role of antiphospholipid antibodies.

3005 Integrin Mac-1 Potentiates Neutrophil Adhesion and NET Release in Antiphospholipid Syndrome

OBJECTIVES/SPECIFIC AIMS: While the role of antiphospholipid antibodies in activating endothelial cells has been extensively studied, the impact of these antibodies on the adhesive potential of leukocytes has received considerably less attention. Mac-1 is a heterodimeric beta-2 integrin primarily expressed by myeloid-lineage cells. In its activated state, Mac-1 mediates cell-cell interactions by engaging a variety of surface molecules, including the endothelium-expressed glycoprotein ICAM-1. Here, our goals were (1) to determine the extent to which APS neutrophils adhere to healthy, resting endothelial cells under physiologic flow conditions, and (2) to identify potential therapeutic targets by elucidating the molecules required for that adhesion. METHODS/STUDY POPULATION: Primary APS patients (meeting Sydney criteria) and non-autoimmune controls were matched for age and gender. Freshly isolated human umbilical vein endothelial cells (HUVECs) were utilized within five passages. Samples were introduced into a flow channel via a programmable syringe pump, and perfused across a resting HUVEC monolayer. After 15 minutes of perfusion, the chamber was flushed, and the remaining adherent cells were quantified. Flow cytometry was used to identify differentially-expressed molecules on the surface of APS neutrophils. Neutrophil extracellular trap (NET) release was assessed in static neutrophil-HUVEC cultures. RESULTS/ANTICIPATED RESULTS: Pre-treating control neutrophils with APS plasma resulted in increased adhesion as compared with control plasma (&gt;2.5-fold for n = 12 plasma samples; p &lt; 0.05). This was true under both venous conditions (low shear) and conditions representative of the microvasculature (pulsatile flow and higher shear). Control neutrophils treated with APS plasma demonstrated upregulation of CD64, CEACAM-1, beta-2 glycoprotein I, and activated Mac-1 on the neutrophil surface, as well as shedding of L-selectin. Upregulation of activated Mac-1 and shedding of L-selectin were also triggered by IgG purified from APS plasma. For these changes to be meaningful clinically, we reasoned that they should be present on neutrophils in the peripheral blood of APS patients. Indeed, perfusion of anticoagulated blood through the flow chamber resulted in increased adhesion of patient neutrophils as compared with controls (&gt;5-fold for n = 18 patients; p &lt; 0.05). Similarly, patient neutrophils demonstrated upregulation of CD64, CEACAM-1, beta-2 glycoprotein I, and activated Mac-1 on the neutrophil surface. A monoclonal antibody specific for activated Mac-1 reduced the adhesion of APS neutrophils to HUVECs in the flow-chamber assay (&gt;2-fold reduction for n = 5 patients; p &lt; 0.05). Importantly, the same monoclonal antibody reduced NET release in neutrophil-HUVEC co-cultures. DISCUSSION/SIGNIFICANCE OF IMPACT: APS neutrophils have an increased adhesive potential, which is dependent upon the activated form of Mac-1. This may lower the threshold for both neutrophil-endothelium engagement and NET release in patients, and thereby have implications for events such as venous thrombosis. Studies are underway to determine the extent to which Mac-1 is a viable therapeutic target in preclinical models of APS.

Pathogenic role of antiphospholipid antibodies: an update.

Pathogenic role of antiphospholipid antibodies: an update.

Potential Roles of Antiphospholipid Antibodies in Generating Platelet-C4d in Systemic Lupus Erythematosus.

Premature, accelerated onset of atherothrombotic disease is prevalent in patients with systemic lupus erythematosus (SLE). Most, if not all, atherothrombotic diseases are likely to involve platelets and complement. Previously, we discovered that platelets bearing complement activation product C4d (P-C4d) are present in SLE patients, and are significantly associated with antiphospholipid (aPL) antibody positivity and stroke in SLE patients. The goal of the present study was to further elucidate the role of aPL and other platelet-reactive autoantibodies in the generation of P-C4d. To determine the association between P-C4d and aPL antibodies, the serum levels of aPL antibodies and P-C4d of 180 SLE patients were measured by enzyme-linked immunoassays and flow cytometry, respectively. To investigate the role of aPL antibodies, and possibly other autoantibodies as well, in mediating the generation of P-C4d, in vitro 2-step P-C4d induction experiments were performed. The results showed that the presence and levels of aPL antibodies in the serum were specifically elevated in SLE patients with positive P-C4d. The plasma and immunoglobulins purified from SLE patients who were positive for P-C4d and aPL were capable of inducing C4d deposition on normal platelets in vitro. The capacity of SLE plasma in inducing P-C4d appeared to correlate proportionately to the serum aPL levels. Collectively, the results demonstrate that both aPL and other platelet-reactive autoantibodies may participate in mediating the generation of P-C4d in SLE patients.

Antiphospholipid antibodies can identify lupus patients at risk of pulmonary hypertension: A systematic review and meta-analysis.

Pulmonary hypertension (PH) is a life-threatening condition that may affect outcomes in patients with systemic lupus erythematosus (SLE). The role of antiphospholipid antibodies (aPL) on the risk of PH is controversial. Therefore our objective was to estimate the risk of PH (WHO groups 1-5) including associated pulmonary arterial hypertension (APAH, WHO group 1 only) related to aPL in patients with SLE. Systematic review and meta-analysis were performed: MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched through 2015. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcomes (PH including APAH). Two reviewers extracted study characteristics and outcome data from published reports. Estimates were pooled using random effects models and sensitivity analyses. PROSPERO registration number: CRD42015016872. Of 984 identified abstracts, 31 primary studies (five cohorts, 13 case-control, 13 cross-sectional) met inclusion criteria, including 4480 SLE patients. Prevalence of PH in aPL-positive vs. aPL-negative SLE patients was 12.3% vs. 7.3%, respectively. The overall pooled odds ratio (OR) for PH was 2.28 (95% CI, 1.65 to 3.15) (I2=39%). The risk of APAH was also significantly increased (OR=2.62 [95% CI, 1.11-6.15]). The risk of PH was the highest for lupus anticoagulant (OR=1.96 [95% CI, 1.31-2.92]) and IgG anticardiolipin antibodies (OR=2.64 [95% CI, 1.30-5.36]) while other antibodies were not significantly associated with PH. Among SLE patients, aPL can identify patients at risk for PH and APAH. These findings warrant implementation of effective screening and early treatment strategies.

Cardiac abnormalities in patients with systemic lupus erythematosus: the role of antiphospholipid antibodies

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course. More than 90% of cases of SLE occur in women, frequently starting at childbearing age. It is characterized by the presence of autoantibodies potentially directed toward every organ or apparatus. Cardiac alterations are frequent in patients affected by SLE and the simultaneous presence of antiphospholipid antibodies (aPL), able to cause arterial thrombosis in any vascular district, is considered a possible risk factor for cardiac damage in SLE patients. The aim of this study is to correlate the main cardiac disorders, estimable through transthoracic echocardiography, in SLE patients as well as the typical autoantibody pattern of the disease. Our study included 76 patients: 38 SLE and 38 controls patients. Control patients have been properly selected to be comparable in gender, age and risks factors for cardiovascular disease. We performed autoantibody panel to assess the prevalence of various autoantibodies during SLE development (antinuclear antibody [ANA], double-stranded DNA [dsDNA], extractable nuclear antigen antibodies [ENA], aPL). In the study, the determination of the IgG and IgM isotypes for aPL (cardiolipin, phosphatidylinositol [aPI], phosphatidylserine, phosphatidic acid [aPA], and anti-β2-glycoprotein I antibodies) were checked. Echocardiography was performed in all patients. In patients affected by SLE, 94.7% was positive to ANA (relative risk 20; 95% confidence interval 4.9-340; p<0.0001) whereas 60.5% was positive for aPL. In patients with SLE, valvular alterations were observed, with a statistically significant correlation between mitral and aortic insufficiency (p=0.01 and p=0.02, respectively). Among aPL-positive patients, 68% (17/25) exhibited at least one hemodynamically significant echocardiographic alteration, vss 3/13 (23%) of patients with negative aPL, with a statistically significant correlation (relative risk 2; 95% confidence interval 1.0-29.8; p=0.01). Among positive-aPL patients, a statistically significant correlation was also observed between mitral insufficiency and aPI-IgG positivity (p=0.01) and, regarding non-valvular alterations, between left atrial enlargement and aPI-IgG positivity (p=0.01) and between left ventricular hypertrophy and aPA-IgG positivity (p=0.03). The present study confirms that SLE is an important risk factor for the presence of cardiac alterations, especially for valvular damage. Moreover, the presence of aPL antibodies in patients with SLE is significantly associated with an increased risk of heart disease, and some specific cardiac alterations are correlated with the positivity of some subclasses of aPL.

Antiphospholipid antibodies and lower extremity peripheral arterial disease - a systematic review and meta-analysis.

Despite being an important risk factor for venous thromboembolism and ischaemic stroke, the role of antiphospholipid antibodies in patients with peripheral arterial disease remains a matter of debate. The aim of this study was to evaluate the association of persistently elevated antiphospholipid antibodies and lower extremity peripheral arterial disease. We conducted a systematic review of electronic databases including MEDLINE, EUROPUBMED and EMBASE to assess the prevalence of antiphospholipid antibodies in patients with lower extremity peripheral arterial disease. Case-control studies were included if they reported the prevalence of antiphospholipid antibodies in patients with lower extremity peripheral arterial disease. Two reviewers (FV and EG) independently assessed the eligibility of all articles. The primary outcome measure was the odds ratio (OR) for the prevalence of antiphospholipid antibodies patients with lower extremity peripheral arterial disease, along with the corresponding 95 % confidence intervals (CIs). Our initial electronic search identified 128 relevant abstracts, of which two studies were included. Antiphospholipid antibodies were found in 50/571 patients with lower extremity peripheral arterial disease and 13/490 of the controls, OR 3.32 (95 % CI = 1.49 to 7.4). In those with critical limb ischaemia, the prevalence of antiphospholipid antibodies was elevated compared to controls, pooled OR 4.78 (95 % CI = 2.37 to 9.65). Our systematic review and meta-analysis suggests that the prevalence of persistently elevated levels of antiphospholipid antibodies is increased in patients with lower extremity peripheral diseases when compared to healthy controls, especially in those with critical limb ischaemia.