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Contour-enhanced funnel plot of the included studies assessing aCL antibodies shows no evidence of publication bias.
Source publication
Behçet's disease (BD) is a multifactorial systemic inflammatory disease of unknown aetiology characterised by several clinical manifestations including vascular involvements (i.e., both arterial and venous thrombosis). Antiphospholipid antibodies (aPLs)-including anticardiolipin (aCL), anti-β2-glycoprotein I (β2-GPI) antibodies and lupus anticoagul...
Contexts in source publication
Context 1
... funnel plot representing the prevalence of aCL antibodies in patients with BD (Fig 6) was used to evaluate publication bias in this meta-analysis. Based on visual inspection of the contour-enhanced funnel plot, it seems that there is no potential publication bias in the studies assessing aCL antibodies. ...
Context 2
... funnel plot representing the prevalence of aCL antibodies in patients with BD (Fig 6) was used to evaluate publication bias in this meta-analysis. Based on visual inspection of the contour-enhanced funnel plot, it seems that there is no potential publication bias in the studies assessing aCL antibodies. ...
Context 3
... funnel plot representing the prevalence of aCL antibodies in patients with BD (Fig 6) was used to evaluate publication bias in this meta-analysis. Based on visual inspection of the contour-enhanced funnel plot, it seems that there is no potential publication bias in the studies assessing aCL antibodies. ...
Citations
... Publication bias and sensitivity analyses were performed using different methods of analysis to investigate the strength of the result following a previous study with slight modifications [17,18]. Primarily, a funnel plot was created to identify the publication bias, followed by a Galbraith plot, which was constructed to visualize any outlier studies. ...
Thalassemia is one of the most prevalent genetic disorders worldwide and has previously been found to have an association with several physiological and organ complications. Several studies have found both its positive and inverse correlation with the glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of β-thalassemia major (β-TM) with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles, we finally included 15 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was −6.94, 95%CI: −20.69, 6.80 (p < 0.00001), which indicated a negative correlation of the GFR with β-TM. The sensitivity analyses found one study to be a slight outlier, and reanalyzing the data excluding that study, an MD was achieved of −16.46, 95%CI: −26.81, −6.11 (p < 0.00001), which provides even stronger support for our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to β-TM patients.
... A value of I 2 close to zero represents homogeneity, whereas, the following ranges of I 2 was used to interpret heterogeneity: I 2 = 25-50%: low heterogeneity, I 2 = 51-75%: moderate heterogeneity, I 2 >75%: high heterogeneity. For visual inspection of publication bias, funnel plot was generated [13]. ...
Introduction: The association between allergy and cancer is contradictory, whereas some forms of cancer have inverse associations with allergy. Allergic rhinitis (AR) is the most prevalent form of allergy, and lung cancer is one of the most prevalent forms of cancer, with the highest percentage of mortality. Recent studies report a positive association between asthma and lung cancer, although that, too, is not conclusive yet. However, AR has a positive association with asthma; therefore, our research question was to explore whether there is any correlation between AR and lung cancer epidemiologically. Methods and Results: Seven eligible articles were found to be eligible for this systematic review and meta-analysis, including 4663 cases and 9056 controls, five from the USA and one each from Canada and Germany. Pooled analysis [OR: 0.56; 95% CI: 0.45-0.70; p-value<0.00001], and [RR: 0.63; 95% CI: 0.51-0.77; p-value<0.00001] depicted a strong inverse relationship between AR and lung cancer. Among small-cell and non-small-cell lung cancer, the inverse association was stronger with Small-cell lung cancer (SCLC): [OR: 0.58, 95% CI: 0.46-0.73], and [RR: 0.64, 95% CI: 0.53-0.77], with a p-value <0.00001; however, this finding was only based on one study among females. The study in Canada (OR: 0.35 and RR: 0.38) and in Germany (OR: 0.18 and RR: 0.19) had lower OR and RR values compared to the studies in the USA (OR 0.62 and RR 0.69). However, two studies in Canada and Germany were the outlier studies in our study, and sensitivity analyses reduced the heterogeneity from 64% to 27% (for OR) and 72% to 40% (for RR) while analyses were conducted eliminating those studies. No low-quality studies were obtained. Conclusion: New epidemiological studies are required to observe the current scenario more comprehensively.
... This vessel inflammation is characterized by mucosal and skin ulcerations in populations with genetic predisposition [84,85]. The most prevalent APLAs in BD are anti-CL and anti-β2-GPI, which are responsible for developing vascular pathologies, such as arterial and venous thrombosis [86]. In rheumatic and musculoskeletal diseases with positive APLA, routine screening for the antibodies is not supported enough by the literature; however, in some conditions like pregnancy planning or thromboembolic events in a patient's history, assessing APLA might be beneficial [78]. ...
Antiphospholipid antibodies (APLAs) are primarily directed toward phospholipid-binding proteins and are responsible for thrombotic events. APLAs include anti-β2Glycoprotein I (anti-β2GPI), anticardiolipin (anti-CL) antibodies, and lupus anticoagulant. These antibodies are typical markers of antiphospholipid syndrome (APS) and are a part of its diagnostic criteria. Many data underline the presence of APLAs in other rheumatic diseases (e.g., systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, rheumatoid arthritis and Behçet’s disease). However, they are also detected in patients with cancer, infection, and neurological disorders. Furthermore, healthy individuals may be carriers of APLAs. Chronic asymptomatic APLAs presence is most common in the elderly and subjects with chronic diseases (including malignancies). Specific kinds of APLAs are considered markers of oncological progression. These antibodies occur in 6% of pregnant women (without diagnosed APS) and are related to many pregnancy complications. Of worth, various types of APLAs are reported to have different prothrombotic properties. The risk of thrombotic events in APLA-positive but clinically naïve patients raises many questions in clinical practice. This manuscript analyses various clinical situations and consequences of the APLAs’ presence, particularly in patients without diagnosed APS. The prevalence, etiology, molecular background, and prothrombotic properties of numerous APLAs are broadly discussed. The new management approach in different clinical conditions and organ complications is present in the context of recent recommendations. Discussed data underlines that adequate and timely introduced thromboprophylaxis can decrease the risk of thrombus formation and prevent increased morbidity.
... Some other non-classical aPLs, such as antiphosphatidylinositol, anti-annexin A5 antiphosphatidylserine, antiphosphatidylethanolamine, and antiprothrombin antibodies, also play a role in the pathogenesis of other diseases [14,15]. The presence of the high titers of aPLs is found in certain medical conditions, including migraine, epilepsy, dementia, Behçet's disease, systemic lupus erythematosus (SLE), and other autoimmune diseases [16][17][18][19]. ...
Simple Summary
Autoimmune diseases cause cancer deaths through thromboembolic events caused by antiphospholipid antibodies. A total of 40 adult cancer patients and 40 age- and sex-matched healthy subjects participated. Blood samples were tested by ELISA methods for anticardiolipin antibodies. Cancer patients had 60.0% (n = 24) aCL antibodies versus none in healthy subjects (p < 0.001). All six lung cancer patients had positive aCL antibodies, and colon cancer patients had a borderline significant association (p = 0.051). In total, 72.7% of advanced-stage cancer and 81.8% of surgery patients had positive aCL antibodies. Cancer patients with cardiovascular comorbidity had higher aCL antibody positivity (p = 0.005).
Abstract
Antiphospholipid antibodies are highly prevalent in autoimmune diseases and mainly associated with thromboembolic events, which is one of the major reasons for cancer-related mortality. Confirmed adult cancer patients were included (n = 40) with an equal number of age- and sex-matched healthy controls. The presence and concentration of anticardiolipin antibodies were investigated by the enzyme-linked immunosorbent assay using the venous blood samples. aCL antibodies were detected in 60.0% (n = 24) of the cancer patients compared to none in the healthy controls (p < 0.001). The serum concentration of aCL antibodies was significantly higher in cancer patients than controls (p < 0.001) and ranged from 89.0 U/mL to 133.0 U/mL among the aCL-positive patients. All the lung cancer patients (n = 6) were diagnosed with positive aCL, and a borderline significant association of aCL antibody positivity was observed in colon cancer patients (p = 0.051). About 72.7% of the advanced-stage cancer individuals and 81.8% of the cancer patients who underwent surgery were diagnosed with positive aCL antibodies. A significant association of aCL antibody positivity was observed with cancer patients comorbid with heart diseases (p = 0.005). The prevalence and serum levels of aCL antibodies were significantly higher in cancer patients compared to healthy controls. Cancer patients (i.e., lung, liver, and colon), at advanced-stage, comorbid with heart diseases, who underwent surgery, were more likely to be diagnosed with aCL antibodies.
... Destruction by anticardiolipin antibodies leads to the formation of a blood clot. Anticardiolipin antibodies have been extensively studied as a clinical manifestation of BD [42]. NAE7:0 is an FA amide involved in innate immunity, cell protection, and inflammation modulation [43]. ...
Background
Behçet’s disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach.
Methods
Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients ( n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs.
Results
Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2.
Conclusions
We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.
... Antiphospholipid (aPL) antibodies are known to induce arterial and venous thromboses, as occurs in antiphospholipid syndrome 95 . A meta-analysis showed a significantly higher prevalence of aPL antibodies in patients with Behçet syndrome than in healthy controls 96 , although whether this increased prevalence is associated with thrombotic manifestations in Behçet syndrome is uncertain 97,98 . Another meta-analysis revealed an increased prevalence of hyperhomocysteinaemia in patients with Behçet syndrome with thrombosis compared with those without thrombosis, particularly in people from the Middle East, Mediterranean regions and Central and Far Eastern Asia 99 , although this increased prevalence was not observed in other studies 100,101 . ...
Behçet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. Vascular involvement, most frequently superficial vein and deep vein thrombosis, can occur in up to 50% of patients with Behçet syndrome. Venous thrombosis at atypical sites (inferior and superior vena cava, suprahepatic veins with Budd-Chiari syndrome, portal vein, cerebral sinuses and right atrium and/or ventricle) and arterial involvement (mostly in situ thrombosis and aneurysms of the pulmonary arteries, as well as aneurysms of the abdominal aorta, and peripheral and visceral arteries) are also unique features of Behçet syndrome. Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome. This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. This Review discusses the main histopathological, pathogenetic and clinical aspects of vascular Behçet syndrome, addressing their implications for therapeutic management. Future perspectives in terms of pathogenetic studies, disease monitoring and treatment strategies are also discussed.
... [1][2][3][4] APS is classified as primary when no clinical or laboratory evidence of another disease is found in the patient; secondary APS is defined when another clinical condition like an autoimmune disease, infection, drugs and/or cancer is present. 3,5 Secondary APS can occur in association with hemolytic anemia, 6,7 immune thrombocytopenic purpura, 8 juvenile arthritis, 3 rheumatoid arthritis, 9 psoriatic arthritis, 3 systemic sclerosis, 10 Behçet syndrome, 11 Sjögren syndrome, 12 polymyositis, 13 dermatoses, 13 rheumatic polymyalgia, 14 systemic lupus erythematosus, 15 eosinophilic myalgia, 3 vasculitis 8 and autoimmune thyroid disease 16 in which the presence of aCL and/or LA have been described. Furthermore, secondary APS has been associated with infectious diseases which trigger the production of aPLs capable of inducing some clinical manifestations such as the catastrophic antiphospholipid syndrome. ...
The antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by a hypercoagulability associated to vascular thrombosis and/or obstetric morbidity, is caused by the presence of antiphospholipid antibodies such as lupus anticoagulant, anti-β-2-glycoprotein 1, and/or anticardiolipin antibodies. In the obstetrical APS, antiphospholipid antibodies induce the production of proinflammatory cytokines and tissue factor by placental tissues and recruited neutrophils. Moreover, antiphospholipid antibodies activate the complement system which, in turn, induces a positive feedback leading to recruitment of neutrophils as well as activation of the placenta. Activation of these cells triggers myometrial contractions and cervical ripening provoking the induction of labor. In thrombotic and obstetrical APS, antiphospholipid antibodies activate endothelial cells, platelets, and neutrophils and they may alter the multimeric pattern and concentration of von Willebrand factor, increase the concentration of thrombospondin 1, reduce the inactivation of factor XI by antithrombin, increase the activation of factor XII, and reduce the activity of tissue plasminogen activator with the subsequent production of plasmin. All these effects result in less permeable clots, denser, thinner, and with more branched fibrin fibers which are more difficult to lysate. As a consequence, thrombosis, the defining clinical criterion of APS, complicates the clinical course of the patient.
... One recently published systematic review and meta-analysis established that there is a significantly higher prevalence of antiphospholipid antibodies in patients with Behcet's disease as compared with controls, which contributes to thrombosis. 13 APS is thought to be a secondary diagnosis, in addition to Behcet's disease, in this case. ...
This case discusses a 10-year-old boy who presented in significant respiratory distress with cardiac tamponade with associated gross ascites and hepatomegaly, requiring urgent transfer for pericardiocentesis. On further investigation, he was found to have multiple pulmonary emboli and evidence of panserositis. An underlying rheumatological cause was suspected in the absence of any evidence of infection or malignancy, and blood tests were positive for anti-double stranded DNA, anticardiolipin and antiglycoprotein antibodies as well as HLA B51. In his medical history, he has previously had mouth ulcers, chronic anaemia of undetermined cause and erythema multiforme. These symptoms, along with clinical presentation, mean a diagnosis of Behcet's disease and associated antiphospholipid syndrome was felt to be most likely. Anticoagulation therapy was commenced for treatment of the emboli, and colchicine was started for management of Behcet's disease. The patient was discharged clinically well from the hospital and continues under specialist rheumatological and haematological follow-up.
... 2 The autoinflammatory theory only partly explains the vessel inflammation and occlusion, and different clinicians investigated the contribution of inherited and acquired thrombophilia to the vascular damage of BD with variable results. [3][4][5] Amongst the former's determinants, the methylenetetrahydrofolate reductase (MTHFR) received some attention 6 : MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate (5,10-MTHF) to 5-methyltetrahydrofolate . The latter provides the methyl group required for regenerating Cob(I)alamin to methylCob(III)alamin, one of the active forms of vitamin B12 and the cofactor which provides the methyl group required for re-methylation of homocysteine (HC) to methionine by 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR, methionine synthase). ...
Aim To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations.
Methods Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes.
Results The search strategy retrieved 48 case–control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls (p < 0.0001) with wide heterogeneity (I2 = 89.7%) that remained unchanged after sensitivity analysis according to year of article publication, age of BD participants, study size, study quality, method of HC determination, and male/female ratio >1.5; some pooled ethnicities explained a small part of the heterogeneity (I2 = 16.3%). Active BD participants had higher HC than inactive ones (p < 0.0001), with moderate heterogeneity (I2 = 49.2%) that disappeared after removal of an outlier study with very high disease activity. BD participants with any vascular involvement had higher HC than those without (p < 0.0001) with wide heterogeneity (I2 = 89.7%); subgroup analysis on venous thrombosis only changed neither effect size (p < 0.0001) nor heterogeneity (I2 = 72.7%). BD participants with ocular involvement had higher HC than those without (p < 0.0001) with moderate heterogeneity (I2 = 40.3%).
Conclusion Although causality cannot be inferred, the consistency of the elevation of plasma HC in BD, particularly in patients with active disease, with vascular and ocular involvement suggests an intrinsic involvement of HC in these clinical manifestations.
... [10] In addition, the prevalence of aCL and anti-β2GPI antibodies has been observed to be significantly higher in patients with Behçet's disease and patients with systemic sclerosis compared to controls. [11,12] Therefore, aPL are routinely measured to assess underlying risk factors for obstetric and/ or thrombotic complications or in the diagnostic work-up for suspected autoimmune diseases. [13] However, data on the prevalence of aPL positivity and characteristics of patients with positive aPL are scarce, due to heterogeneity of aPL-related clinical manifestations and differences in laboratory testing. ...
Objective
Lupus anticoagulant (LAC) and antiphospholipid antibodies (aPL), both further summarized as aPL, are frequently assessed in routine daily clinical practice in diagnostic work-up for suspected autoimmune diseases or to test for underlying risk factors in patients with thrombosis or obstetric complications. The aim of this study is to determine the prevalence of aPL positivity in patients with an indication for aPL testing in routine clinical practice.
Methods
In this retrospective single center study indication for aPL testing, aPL test results and clinical data were collected for patients tested between June 2015 and April 2018.
Results
During the study period, 16,847 single aPL tests were performed in 2,139 patients. In 212 patients ≥1 positive aPL test was found, confirmed in 43.9% with a second positive test. Indications for aPL testing were diagnostic work-up/follow-up of autoimmune diseases (33.6%), thrombosis (21.4%) and obstetrical complications (28%). Seventy-four patients (3.5% of all patients) fulfilled the criteria of the antiphospholipid syndrome (APS), of whom 51% were newly diagnosed. Second positive aPL titers and titers of APS patients were significantly higher compared with positive aPL titers at first measurement (p < 0.05). Patients with indication arterial thrombosis and diagnostic work-up/follow-up of autoimmune diseases had significantly higher levels of aCL IgG and anti-β2GPI IgG compared with patients with other indications.
Conclusion
Prevalence of ≥ 1 positive aPL test was 9.9% and APS was diagnosed in 3.5% of the patients. Patients with arterial thrombosis had significantly higher anti-β2GPI IgG and aCL IgG, which should be confirmed in future studies.
