Background： Antiphospholipid syndrome （APS）-related immune factors are considered as an important cause of recurrent spontaneous abortion （RSA）. Anticoagulant and anti-inflammatory treatments are believed to effe...Background： Antiphospholipid syndrome （APS）-related immune factors are considered as an important cause of recurrent spontaneous abortion （RSA）. Anticoagulant and anti-inflammatory treatments are believed to effectively improve adverse pregnancy outcomes by affecting the abnormal autoimmune response of the maternal-fetal interface. The aim of this study was to observe the clinical characteristics and treatment outcomes of anticoagulant regimens and anti-inflammatory plus anticoagulation regimens for APS-related RSA. Methods： APS-related RSA cases from September 2011 to September 2016 at Peking University Third Hospital were retrospectively analyzed. The patients were assigned to study group （anti-inflammation plus anticoagulation） and control group （simple anticoagulation）, The incidence of repeat abortion, the incidence of placental dysfunction, the gestational weeks of pregnancy, and the mean weight of the fetus were observed. Results： The pregnancy and neonatal outcome indicators of the repeat pregnancy loss rate （ 11. 11% vs. 22.70%）, placental dysfunction-related diseases （6.35% vs. 15.60%）, the mean birth weight of infants born after 24 weeks gestation （3152.4 ± 844.67 g vs. 2765.76 ± 816.40 g）, full-ternl delivery weight （3456.28 ±419.79 g vs. 3076.18±518.79 g）, the proportions of low birth weight infants （ 12.70% vs. 21.98%）, and small for gestational age （6.35% vs. 14.18%） differed significantly between the study and control groups （all P 〈 0.05）. The incidence of preterm delivery, term delivery, and stillbirth was not significantly different between the two groups, and there was no significant difference between the study and control groups in gestational age at birth （37.6 ± 3.3 weeks vs. 36.9 ± 3.2 weeks： P 〉 0.05）. Conclusion： The anti-inflammatory and anticoagulation regimen is more effective than the simple anticoagulation regimen in the treatlnent of APS recurrent abortion.展开更多
Background： The management of patients with recurrent miscarriage （RM） and antiphospholipid antibody syndrome （APS） includes prolonged treatment with heparin and aspirin, starting from the confirmation of pregnan...Background： The management of patients with recurrent miscarriage （RM） and antiphospholipid antibody syndrome （APS） includes prolonged treatment with heparin and aspirin, starting from the confirmation of pregnancy and continuing until 6 weeks after birth. This study was conducted to determine the relationship between changes in antiphospholipid antibody titers and clinical outcomes. The effect of a shortened treatment regimen was also evaluated. Methods： A prospective study of 123 patients with RM and APS between March 2012 and May 2014 was conducted. Patients were pretreated with a low dose of prednisone plus aspirin before pregnancy, and heparin was added after conception. The levels of antiphospholipid antibodies and pregnancy outcomes were evaluated. Results： All patients were positive for anti-β2-glycoprotein 1 （anti-β2-GP 1） IgM. Atier prepregnancy treatment with low-dose prednisone plus aspirin, 99 of 123 patients became pregnant, and 87 of those pregnancies resulted in successful live births, while 12 resulted in miscarriage, showing a success rate of 87.9%. In the live birth group, levels of anti-β2-GP1 were 56.8±49.0 RU/ml before the pretreatment regimen, 32. 1± 26.0 RU/ml after 2 months of pretreatment, and 24.1 ± 23. IRU/ml during early pregnancy （P 〈 0.05）. In the miscarriage group, antiphospholipid antibody titers were 52.8 ±30.7 RU/ml before pretreatment, 38.5 ±34.2 RU/ml after pretreatment, and 33.9 ±24.7 RU/ml during early pregnancy; the decrease in antiphospholipid antibodies was lower in the miscarriage group than in the live birth group （P 〈 0.05）. Of the 24 inferthe patients, the average antibody titer did not decline after pretreatment （P = 0.802）. Conclusions： Anti-[32-GP1 IgM was the predominant form of antibody in patients with RM and APS. The decreases in antiphospholipid antibody titers correlated with better pregnancy outcomes. The shorter treatment regimen was effective and economical.展开更多
Antiphospholipid syndrome (APS) is a thromboinflammatory disease with a variety of clinical phenotypes. Primary thrombosis prophylaxis should take an individualized risk stratification approach. Moderate-intensity vit...Antiphospholipid syndrome (APS) is a thromboinflammatory disease with a variety of clinical phenotypes. Primary thrombosis prophylaxis should take an individualized risk stratification approach. Moderate-intensity vitamin K antagonist such as warfarin remains the primary strategy for secondary thrombosis prophylaxis among APS patients, especially for patients with predominantly venous disease. For now, direct oral anti-coagulants should be avoided in most APS patients, especially those with history of arterial manifestations. Obstetric APS management should be tailored based on an individual patient’s antiphospholipid antibody profile, and obstetric and thrombotic history. Pharmacological agents beyond anticoagulants may be considered for the management of microthrombotic and nonthrombotic manifestations of APS, although more data are needed. A relatively recent discovery in the area of APS pathogenesis is the implication of neutrophil extracellular traps in thrombin generation and initiation of inflammatory cascades. APS is a complex thromboinflammatory disease with a broad clinical spectrum. Personalized therapy according to an individual’s unique thrombosis and obstetric risk should be advocated.展开更多
Thrombotic events,both arterial and venous,are a major health concern worldwide. Further,autoimmune diseases,such as systemic lupus erythematosus,anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis,and an...Thrombotic events,both arterial and venous,are a major health concern worldwide. Further,autoimmune diseases,such as systemic lupus erythematosus,anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis,and antiphospholipid syndrome,predispose to thrombosis,and thereby push the risk for these morbid events even higher. In recent years,neutrophils have been identified as important players in both arterial and venous thrombosis. Specifically,chromatin-based structures called neutrophil extracellular traps(NETs) play a key role in activating the coagulation cascade,recruiting platelets,and serving as scaffolding upon which the thrombus can be assembled. At the same time,neutrophils and NETs are emerging as important mediators of pathogenic inflammation in the aforementioned autoimmune diseases. Here,we first review the general role of NETs in thrombosis. We then posit that exaggerated NET release contributes to the prothrombotic diatheses of systemic lupus erythematosus,ANCA-associated vasculitis,and antiphospholipid syndrome.展开更多
Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations.As a result,they can present great clinical challenges and evoke questi...Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations.As a result,they can present great clinical challenges and evoke questions about diagnostic criteria for liver diseases.Moreover,discriminating between liver involvement as a manifestation of connective tissue disease and primary liver disease can be challenging since they share a similar immunological mechanism.Most patients with connective tissue diseases exhibit liver test abnormalities that likely result from coexisting,primary liver diseases,such as fatty liver disease,viral hepatitis,primary biliary cirrhosis,autoimmune hepatitis,and drug-related liver toxicity.Liver damage can be progressive,leading to cirrhosis,complications of portal hypertension,and liver-related death,and,therefore,must be accurately identified.In this review,we highlight the challenges facing the diagnosis of liver damage associated with connective tissue disease and identify immune mechanisms involved in liver damage associated with connective tissue diseases.展开更多
Kidney is a major target organ in both antiphospholipid syndrome(APS)and systemic lupus erythematosus(SLE).The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis(APSN-LN)is intricate and rema...Kidney is a major target organ in both antiphospholipid syndrome(APS)and systemic lupus erythematosus(SLE).The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis(APSN-LN)is intricate and remains largely unrevealed.We proposed in present work,that generation of antiphospholipid antibodies(aPLs),especially those directed towards the oxidized neoepitopes,are largely linked with the redox status along with disease progression.Moreover,we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN.SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties.In current study,we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice,a murine model develops syndrome resembled human APS associated with SLE,for the first time.SM934 treatment comprehensively impeded autoantibodies production,inflammatory cytokine accumulation and excessive oxidative stress in kidney.Among others,we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets.Collectively,our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.展开更多
文摘Background： Antiphospholipid syndrome （APS）-related immune factors are considered as an important cause of recurrent spontaneous abortion （RSA）. Anticoagulant and anti-inflammatory treatments are believed to effectively improve adverse pregnancy outcomes by affecting the abnormal autoimmune response of the maternal-fetal interface. The aim of this study was to observe the clinical characteristics and treatment outcomes of anticoagulant regimens and anti-inflammatory plus anticoagulation regimens for APS-related RSA. Methods： APS-related RSA cases from September 2011 to September 2016 at Peking University Third Hospital were retrospectively analyzed. The patients were assigned to study group （anti-inflammation plus anticoagulation） and control group （simple anticoagulation）, The incidence of repeat abortion, the incidence of placental dysfunction, the gestational weeks of pregnancy, and the mean weight of the fetus were observed. Results： The pregnancy and neonatal outcome indicators of the repeat pregnancy loss rate （ 11. 11% vs. 22.70%）, placental dysfunction-related diseases （6.35% vs. 15.60%）, the mean birth weight of infants born after 24 weeks gestation （3152.4 ± 844.67 g vs. 2765.76 ± 816.40 g）, full-ternl delivery weight （3456.28 ±419.79 g vs. 3076.18±518.79 g）, the proportions of low birth weight infants （ 12.70% vs. 21.98%）, and small for gestational age （6.35% vs. 14.18%） differed significantly between the study and control groups （all P 〈 0.05）. The incidence of preterm delivery, term delivery, and stillbirth was not significantly different between the two groups, and there was no significant difference between the study and control groups in gestational age at birth （37.6 ± 3.3 weeks vs. 36.9 ± 3.2 weeks： P 〉 0.05）. Conclusion： The anti-inflammatory and anticoagulation regimen is more effective than the simple anticoagulation regimen in the treatlnent of APS recurrent abortion.
文摘Background： The management of patients with recurrent miscarriage （RM） and antiphospholipid antibody syndrome （APS） includes prolonged treatment with heparin and aspirin, starting from the confirmation of pregnancy and continuing until 6 weeks after birth. This study was conducted to determine the relationship between changes in antiphospholipid antibody titers and clinical outcomes. The effect of a shortened treatment regimen was also evaluated. Methods： A prospective study of 123 patients with RM and APS between March 2012 and May 2014 was conducted. Patients were pretreated with a low dose of prednisone plus aspirin before pregnancy, and heparin was added after conception. The levels of antiphospholipid antibodies and pregnancy outcomes were evaluated. Results： All patients were positive for anti-β2-glycoprotein 1 （anti-β2-GP 1） IgM. Atier prepregnancy treatment with low-dose prednisone plus aspirin, 99 of 123 patients became pregnant, and 87 of those pregnancies resulted in successful live births, while 12 resulted in miscarriage, showing a success rate of 87.9%. In the live birth group, levels of anti-β2-GP1 were 56.8±49.0 RU/ml before the pretreatment regimen, 32. 1± 26.0 RU/ml after 2 months of pretreatment, and 24.1 ± 23. IRU/ml during early pregnancy （P 〈 0.05）. In the miscarriage group, antiphospholipid antibody titers were 52.8 ±30.7 RU/ml before pretreatment, 38.5 ±34.2 RU/ml after pretreatment, and 33.9 ±24.7 RU/ml during early pregnancy; the decrease in antiphospholipid antibodies was lower in the miscarriage group than in the live birth group （P 〈 0.05）. Of the 24 inferthe patients, the average antibody titer did not decline after pretreatment （P = 0.802）. Conclusions： Anti-[32-GP1 IgM was the predominant form of antibody in patients with RM and APS. The decreases in antiphospholipid antibody titers correlated with better pregnancy outcomes. The shorter treatment regimen was effective and economical.
基金Dr.Knight is supported by a pilot grant for preclinical studies from Jazz Pharmaceuticals。
文摘Antiphospholipid syndrome (APS) is a thromboinflammatory disease with a variety of clinical phenotypes. Primary thrombosis prophylaxis should take an individualized risk stratification approach. Moderate-intensity vitamin K antagonist such as warfarin remains the primary strategy for secondary thrombosis prophylaxis among APS patients, especially for patients with predominantly venous disease. For now, direct oral anti-coagulants should be avoided in most APS patients, especially those with history of arterial manifestations. Obstetric APS management should be tailored based on an individual patient’s antiphospholipid antibody profile, and obstetric and thrombotic history. Pharmacological agents beyond anticoagulants may be considered for the management of microthrombotic and nonthrombotic manifestations of APS, although more data are needed. A relatively recent discovery in the area of APS pathogenesis is the implication of neutrophil extracellular traps in thrombin generation and initiation of inflammatory cascades. APS is a complex thromboinflammatory disease with a broad clinical spectrum. Personalized therapy according to an individual’s unique thrombosis and obstetric risk should be advocated.
基金Supported by NIH K08AR066569a career development award from the Burroughs Wellcome Fund(Knight JS)Kazzaz NM was supported by Security Forces Hospital Program,Ministry of Interior,Riyadh,Saudi Arabia
文摘Thrombotic events,both arterial and venous,are a major health concern worldwide. Further,autoimmune diseases,such as systemic lupus erythematosus,anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis,and antiphospholipid syndrome,predispose to thrombosis,and thereby push the risk for these morbid events even higher. In recent years,neutrophils have been identified as important players in both arterial and venous thrombosis. Specifically,chromatin-based structures called neutrophil extracellular traps(NETs) play a key role in activating the coagulation cascade,recruiting platelets,and serving as scaffolding upon which the thrombus can be assembled. At the same time,neutrophils and NETs are emerging as important mediators of pathogenic inflammation in the aforementioned autoimmune diseases. Here,we first review the general role of NETs in thrombosis. We then posit that exaggerated NET release contributes to the prothrombotic diatheses of systemic lupus erythematosus,ANCA-associated vasculitis,and antiphospholipid syndrome.
文摘Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations.As a result,they can present great clinical challenges and evoke questions about diagnostic criteria for liver diseases.Moreover,discriminating between liver involvement as a manifestation of connective tissue disease and primary liver disease can be challenging since they share a similar immunological mechanism.Most patients with connective tissue diseases exhibit liver test abnormalities that likely result from coexisting,primary liver diseases,such as fatty liver disease,viral hepatitis,primary biliary cirrhosis,autoimmune hepatitis,and drug-related liver toxicity.Liver damage can be progressive,leading to cirrhosis,complications of portal hypertension,and liver-related death,and,therefore,must be accurately identified.In this review,we highlight the challenges facing the diagnosis of liver damage associated with connective tissue disease and identify immune mechanisms involved in liver damage associated with connective tissue diseases.
基金supported by the National Natural Science Foundation of China(81903882 and 81871240)the National Science and Technology Major Project“New Drug Creation and Manufacturing Program”(2018ZX09711002-014-001)the Personalized Medicines——“Molecular Signature-based Drug Discovery and Development”,Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12020107 and XDA12020369).
文摘Kidney is a major target organ in both antiphospholipid syndrome(APS)and systemic lupus erythematosus(SLE).The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis(APSN-LN)is intricate and remains largely unrevealed.We proposed in present work,that generation of antiphospholipid antibodies(aPLs),especially those directed towards the oxidized neoepitopes,are largely linked with the redox status along with disease progression.Moreover,we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN.SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties.In current study,we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice,a murine model develops syndrome resembled human APS associated with SLE,for the first time.SM934 treatment comprehensively impeded autoantibodies production,inflammatory cytokine accumulation and excessive oxidative stress in kidney.Among others,we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets.Collectively,our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.
