Antiphospholipid syndrome

Antiphospholipid syndrome is an autoimmune systemic disorder characterized by arterial, venous, or small vessel thrombosis and/or recurrent early pregnancy loss, fetal loss, or pregnancy morbidity in the setting of documented persistent antiphospholipid antibodies that include the lupus anticoagulant, or moderate-high titer anticardiolipin, or anti-β2Glycoprotein I antibodies. Associated clinical manifestations include livedo reticularis, cutaneous ulcerations, thrombocytopenia, hemolytic anemia, valvular heart disease, and nephropathy. The degree of risk associated with antiphospholipid antibody depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. Current standard treatment for unprovoked thrombosis is long-term warfarin or other vitamin K antagonist therapy. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin, usually low-molecular-weight heparin. Optimal treatment for standard therapy failures or for certain nonthrombotic manifestations is uncertain, although nonanticoagulation therapies that address multiple demonstrated mechanisms of disease are being explored.     

Cierre de la orejuela izquierda por ictus pese a la anticoagulación oral (ictus resistente): resultados del registro Amplatzer Cardiac Plug

Introduction and objectivesDespite the efficacy of oral anticoagulant (OAC) therapy, some patients continue to have a high residual risk and develop a stroke on OAC therapy (resistant stroke [RS]), and there is a lack of evidence on the management of these patients. The aim of this study was to analyze the safety and efficacy of left atrial appendage occlusion (LAAO) as secondary prevention in patients with nonvalvular atrial fibrillation who have experienced a stroke/transient ischemic attack despite OAC treatment.MethodsWe analyzed data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients with nonvalvular atrial fibrillation undergoing LAAO. Patientes with previous stroke on OAC therapy as indication for LAAO were identified and compared with patients with other indications.ResultsA total of 115 patients (11%) with RS were identified. The CHA₂DS₂-VASc and the HAS-BLED score were significantly higher in the RS group (respectively 5.5 ± 1.5 vs 4.3 ± 1.6; P < .001; 3.9 ± 1.3 vs 3.1 ± 1.2; P < .001). No significant differences were observed in periprocedural major safety events (7.8 vs 4.5%; P = .1). With a mean clinical follow-up of 16.2 ± 12.2 months, the observed annual stroke/transient ischemic attack rate for the RS group was 2.6% (65% risk reduction) and the observed annual major bleeding rate was 0% (100% risk reduction).ConclusionsPatients with RS undergoing LAAO showed similar safety outcomes to patients without RS, with a significant reduction in stroke/transient ischemic attack and major bleeding events during follow-up. Adequately powered controlled trials are needed to further investigate the use of LAAO in RS patients.     

Specificities of platelet autoantibodies in patients with lupus anticoagulants in primary antiphospholipid syndrome

 We have studied target platelet antigens in 22 patients with lupus anticoagulants and a primary antiphospholipid syndrome in order to determine whether any specificities of platelet autoantibodies are correlated with thromboembolism, and if these antibodies cross-reacte with phospholipids, which would suggest their role in the development of thromboembolic disease. Platelet counts were median 203×10⁹/l, range 100–298×10⁹/l. Platelet antibodies were found in six thrombocytopenic patients and in further nine patients. All these 15 patients had antibodies against GPIIb/IIIa, five patients against GPIb/IX, and six patients against GPIV. Anti-GPIb/IX and -GPIV occurred only in combination with anti-GPIIb/IIIa antibodies. There was no correlation between the presence of detectable platelet antibodies or any of their glycoprotein specificity and thrombocytopenia or the history of a thromboembolic disease. Eluates from platelets contained only GPIIb/IIIa reactivities, but neither anti-GPIb/IX nor anti-GPIV. None of the eluates contained lupus anticoagulant activity. In one case, the platelet eluates contained anti-GPIIb/IIIa and anticardiolipin IgG antibodies. These results suggest that in patients with a primary antiphospholipid syndrome the presence of platelet autoantibodies neither indicate a risk for thromboembolic disorder nor have lupus anticoagulant activity. Received: 27 January 1997 / Accepted: 10 March 1997     

多维健康评定量表在中国系统性红斑狼疮人群中的信度及效度研究

目的 评估中文版多维健康评定量表(MDHAQ-C)在中国SLE人群生活质量测量中的信度及效度.方法 招募SLE患者1 12例,信度分析采用组内相关系数(ICC)重测信度及克隆巴赫系数α内部一致性评估.聚合效度通过比较MDHAQ各维度得分与健康评定问卷(HAQ)、医院焦虑抑郁量表(HAD)及简明健康状况调查表(SF-36)的Spearman相关分析进行评估相关性评价.区分效度通过比较不同组别患者各维度得分差异进行Mann-Whitney检验进行分析.结果 在维度层面,克隆巴赫系数α分别为0.886及0.774;在条目层面,条目校正的项总计相关系数0.409～0.866.重测信度各维度组内相关系数值ICC范围0.615～0.920(P＜0.05).MDHAQ中文版大部分维度与HAQ、HAD及SF-36的相关性较好(P＜0.5至P＜0.001).针对不同疾病活动度及损伤程度的患者,MDHAQ不同维度得分差异有统计学意义(P＜0.05)区分效度.结论 MDHAQ中文版信度、效度良好,可作为躯体功能及生活质量的测评工具,用于中国SLE人群.     

Lupus Myocarditis: A Case–Control Study from China

Background:

Myocarditis is an uncommon but serious manifestation of systemic lupus erythematosus (SLE). This study aimed to investigate clinical characteristics and outcomes of lupus myocarditis (LM) and to determine risk factors of LM in hospitalized Chinese patients with SLE.

Methods:

We conducted a retrospective case–control study. A total of 25 patients with LM from 2001 to 2012 were enrolled as the study group, and 100 patients with SLE but without LM were randomly pooled as the control group. Univariable analysis was performed using Chi-square tests for categorical variables, and the Student''s t-test or Mann–Whitney U-test was performed for continuous variables according to the normality.

Results:

LM presented as the initial manifestation of SLE in 7 patients (28%) and occurred mostly at earlier stages compared to the controls (20.88 ± 35.73 vs. 44.08 ± 61.56 months, P = 0.008). Twenty-one patients (84%) experienced episodes of symptomatic heart failure. Echocardiography showed that 23 patients (92%) had decreased left ventricular ejection fraction (<50%) and all patients had wall motion abnormalities. A high SLE Disease Activity Index was the independent risk factor in the development of LM (odds ratio = 1.322, P < 0.001). With aggressive immunosuppressive therapies, most patients achieved satisfactory outcome. The in-hospital mortality was not significantly higher in the LM group than in the controls (4% vs. 2%,P = 0.491).

Conclusions:

LM could result in cardiac dysfunction and even sudden death. High SLE disease activity might potentially predict the occurrence of LM at the early stage of SLE. Characteristic echocardiographic findings could confirm the diagnosis of LM. Early aggressive immunosuppressive therapy could improve the cardiac outcome of LM.     

高迁移率族蛋白1对狼疮肾炎小鼠肾小球细胞增殖的影响

目的 通过敲低肾组织高迁移率族蛋白1(HMGB1)表达,探讨其对改善狼疮肾炎小鼠肾功能,降低肾小球细胞增殖水平的影响.方法 MRL/Faslpr鼠(n=24)被随机分为模型组、shHMGB1组和空质粒组;选取周龄、体质量相匹配的MRL/MpJ鼠为健康对照组.shHMGB1组和空质粒组采用电穿孔转染技术分别转染shHMGB1质粒和空质粒,模型组和健康对照组仅转染生理盐水.用全自动生化分析仪检测小鼠血清尿素氮和肌酐水平,测定尿蛋白浓度并计算24 h尿蛋白量(UP).HE染色观察肾组织的形态学表现;免疫荧光和Western印迹法检测小鼠肾小球中HMGB1和增殖细胞核抗原(PCNA)的表达;实时定量PCR法检测小鼠肾小球HMGB1和PCNA mRNA表达变化.结果 (1)与健康对照组相比,模型组小鼠肾小球HMGB1 mRNA和蛋白的表达升高(均P＜0.05);与模型组相比,shHMGB1组小鼠肾小球中HMGB1 mRNA和蛋白的表达降低(均P＜0.05).(2)与模型组相比,shHMGB1组小鼠尿蛋白减少(P＜0.05).(3)免疫荧光和Western印迹结果显示,与健康对照组相比,模型组小鼠肾小球中PCNA mRNA和蛋白表达升高(P＜0.05).与模型组相比,shHMGB1组肾小球中PCNA表达降低(P＜0.05).结论 敲低肾组织HMGB1表达可改善狼疮肾炎小鼠的肾功能,降低肾小球细胞的增殖水平.     

系统性红斑狼疮合并甲状腺功能异常的临床分析

目的：探讨系统性红斑狼疮（ SLE）与甲状腺疾病之间的相关性。方法以186例完善甲状腺功能检查的SLE患者为研究对象,并以200例健康体健人群为对照组,比较甲状腺功能异常情况,甲状腺球蛋白抗体TGAb及抗甲状腺过氧化物酶TPOAb阳性率以及评估狼疮临床活动度。结果①甲状腺功能异常在SLE组发生率为28．5％,显著高于对照组7％,差异具有统计学意义（ P ＜0．05）;②SLE 组 TGAb阳性率16．7％,TPOAb阳性率25．8％,高于对照组中TGAb阳性率6％,TPOAb阳性率9％,两组差异具有统计学意义（ P ＜0．05）;③SLE组行SLEDAI评分,甲状腺功能正常组（8．2±4．7）分,甲状腺功能异常组（7．9±5．8）分,两组间差异无统计学意义（ P ＞0．05）;④甲状腺抗体阳性组SLEDAI评分（8．3±5．7）与抗体阴性组（7．9±6．4）相比,两组间差异无统计学意义（ P ＞0．05）。结论甲状腺功能异常、甲状腺抗体阳性在SLE患者中有较高的发病率,但与狼疮疾病活动无明显相关性, SLE 患者随访中需常规行甲状腺功能检查,重视甲状腺疾病诊治。     

Correlation Between Quantitative Anti-dsDNA Levels with Severity of Proteinuria in Systemic Lupus Erythematosus Patients

ObjectiveTo evaluate the correlation of quantitative anti-dsDNA level with proteinuria levels in patients with lupus nephritis in a tertiary care hospital.Study designIn this prospective cross-sectional study, 76 patients of newly diagnosed SLE coming to Fatima Memorial Hospital were included in the study period between January 2020 to June 2020. Demographic data such as age, gender, lupus manifestations such as serositis, arthritis, mucocutaneous disease, and neuropsychiatric manifestations were recorded. Quantitative anti-dsDNA was measured by enzyme-linked immunosorbent assay and proteinuria was estimated by 24 h urinary protein collection. Data was analyzed by SPSS 23. Association between categorical variables was assessed using chi-square test. For comparison of categorical independent and continuous dependent variable t-test or Mann–Whitney U test was applied.ResultsThe median age of the cohort was 29 (with inter quartile range – IQR – of 13) years. The female gender comprised of 68 (89.4%) of the cohort population. The median anti-dsDNA level was 54.9 (183.6 IQR) IU, and baseline proteinuria of the cohort was 520 mg/dL (1.49 IQR). There was a significant association of anti-dsDNA level with systemic features such as arthritis (p = <0.01), serositis (p = <0.01) and, Raynaud's phenomenon (p = <0.01). NPSLE and mucocutaneous features did not show statistically significant association (p = 0.91 and 0.14 respectively). Baseline anti-dsDNA showed a statistically significant correlation with baseline proteinuria levels (p = <0.01).ConclusionQuantitative anti-dsDNA is directly correlated with nephritis measured as proteinuria, and can be detected even before organ involvement. Hence, it can determine disease course and guide early treatment.     

Relación de la expresión génica de IP-10 con la actividad del lupus eritematoso sistémico

ObjectivesTo evaluate IP-10 gene expression in patients with SLE, and its possible relationship with disease activity.Patients and methodsThis study included 120 patients diagnosed with SLE and 30 healthy controls. The relative gene expression of IP-10 was investigated with the Fold Change method, which was correlated with the level of lupus activity evaluated with the SLEDAI 2-K instrument.ResultsDifferent levels of gene expression were found according to the SLE activity (p =<0.001). IP-10 gene expression levels were higher in patients with severe activity than in those with no activity, low activity, and moderate activity. The increase in gene expression in the severe activity group was significant with a Fold Change of 3.ConclusionThe significant increase in relative gene expression IP-10 may be a marker of severe lupus activity.