Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.     

抗环瓜氨酸肽抗体与系统性红斑狼疮关节炎的相关性研究

目的 研究抗环瓜氨酸肽(CCP)抗体在系统性红斑狼疮(SLE)患者中的临床意义,探讨抗CCP抗体与SLE患者关节炎及骨侵蚀的关系.方法 采用酶联免疫吸附试验(ELISA)方法检测138例SLE患者血清中抗CCP抗体水平,并与SLE患者关节表现及其他临床指标进行相关性分析.结果 抗CCP抗体在SLE患者中的阳性率为13.8%(19/138).SLE患者关节炎的发生率为50.7%,关节炎组抗CCP抗体阳性率(20%)高于非关节炎组(7.4%)(P＜0.05).在SLE关节炎患者中,抗CCP抗体阳性者类风湿因子(RF)阳性率显著高于抗CCP抗体阴性者(71.4%与14.3%)(P＜0.01).而且,抗CCP抗体与RF之间显著相关(r=0.36,P=0.002).抗CCP抗体阳性的SLE患者关节炎的发生率明显高于抗CCP抗体阴性者(73.7%与47.1%,P＜0.05).138例SLE患者中有8例出现受累关节的影像学改变,与抗CCP抗体阴性患者相比,抗CCP抗体阳性患者表现出侵蚀性关节炎的比例显著为高(35.7%与5.4%,P＜0.01).在8例表现为侵蚀性关节炎的患者中有2例患者抗CCP抗体和RF均阴性,而抗RA33抗体阳性.此8例患者均满足美国风湿病学学会(ACR)1987年类风湿关节炎(RA)的分类标准.SLE相关其他临床指标分析显示,关节炎组.与非关节炎组、抗CCP抗体阳性组与阴性组之间差异均无统计学意义.结论 13.8%的SLE患者体内存在抗CCP抗体.抗CCP抗体的出现与SLE患者关节炎和骨侵蚀密切相关,并对判断SLE关节炎的预后具有重要的临床价值.     

Anti-platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia

The role of antiphospholipid antibodies in the pathogenesis of the thrombocytopenia observed during primary antiphospholipid antibody syndrome (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used the MAIPA test to examine the frequency and specificity of anti-platelet antibodies directed against the major platelet membrane glycoproteins (GP IIb–IIIa, GP Ib–IX, GP Ia–IIa and GP IV) in patients where SLE and APAS were associated or not with thrombocytopenia. Results were compared with a series of 26 ITP patients, 46% of whom were shown to possess anti-platelet antibodies directed against one or more of the platelet surface glycoproteins. When APAS was associated with thrombocytopenia, 7/10 patients possessed antibodies against GP IIb–IIIa and/or GP Ib–IX. For SLE patients with thrombocytopenia, 6/10 patients were shown to have antiplatelet antibodies against GP IIb–IIIa, GP Ib–IX or GP IV. In contrast, for APAS ( n =11) and SLE patients ( n =11) without thrombocytopenia, only one patient had an antibody directed against GP IIb–IIIa and one patient had an antibody to GP IV. Our results suggest that antibodies directed against major platelet membrane glycoproteins may play a role in the thrombocytopenia that is seen during SLE and APAS.     

Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome

Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregnancy. Moreover, the relationship between SLE and pregnancy is in both directions. However, the current experience indicates that pregnancy in patients with SLE should not be regarded as an unacceptable high risk condition for the mother or her baby provided that careful planning of conception and multidisciplinary monitoring and treatment are carried out.     

Infections in patients with systemic lupus erythematosus

Infection is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). In most clinical series, infection ranks first or second as the most common cause of death in SLE patients worldwide, including Hong Kong. In this article, the spectrum of infections and their protean manifestations in lupus patients will be reviewed with emphasis on clinical data from Hong Kong and other Asian countries. A high index of suspicion and dedicated work‐up to identify the causative pathogens is pivotal to the early diagnosis and effective management of infective complications in patients with SLE.     

Massive hepatic infarction in systemic lupus erythematosus

Summary Liver disease in systemic lupus erythematosus, as demonstrated by abnormal histopathology, is rare and usually mild; typically, this hepatic disease is of chronic nature and not related to a hypercoagulable state. A patient is described in whom life-threatening hypercoagulability in association with systemic lupus erythematosus resulted in extensive liver infarction. Follow-up radionuclide liver scintigraphy suggested that regenerative recovery in the infarcted areas of the liver may be delayed or absent, but there was no evident functional hepatic impairment.     

抗血小板生成素抗体与系统性红斑狼疮伴血小板减少的相关性研究

目的 分析抗血小板生成素(TPO)抗体在系统性红斑狼疮(SLE)中的作用,并探讨其与SLE伴血小板减少及病情的相关性.方法 应用酶联免疫吸附试验(ELISA)检测56例SLE患者中的抗TPO抗体,并与20例免疫性血小板减少性紫癜(ITP)及20名健康人对照.同时分析SLE患者临床特点.正态分布的计数资料采用x2检验或Fisher精确检验,计量资料采用t检验,非正态分布采用M(Q)表示及Wilcoxon's rank检验.结果 抗TPO抗体在SLE组中阳性率为39％,35％的免疫性血小板减少患者抗TPO抗体阳性,而健康对照中未能检测到抗TPO抗体(x2=11.058,P=0.001).26例伴发血小板减少的SLE患者中,15例(58％)抗TPO抗体阳性,而30例无血小板减少患者中仅有7例(23％,x2=6.894,P=0.009);进一步分析发现抗TPO体抗体阳性患者其血小板下降程度重(t=3.010,P=0.004).对照抗TPO抗体阳性与阴性患者的临床资料显示,关节炎(x2=5.959,P=0.015)、抗双链DNA(dsDNA)抗体阳性(x2=5.959,P=0.015)的SLE患者更易产生抗TPO抗体.结论 在伴发血小板减少的SLE患者中检测出较高阳性率的抗TPO抗体表明该抗体可能在SLE发生血小板减少的过程中起重要作用.在伴发血小板减少的SLE患者中检测该抗体具有一定的临床价值.     

抗β2-糖蛋白Ⅰ抗体在系统性红斑狼疮中的临床意义

目的了解抗!2-糖蛋白Ⅰ抗体(抗!2-GPⅠ抗体)与系统性红斑狼疮(SLE)临床特点的关系及在其诊断中的价值。方法采用酶联免疫吸附试验(ELISA)检测112例SLE患者、40例类风湿关节炎(RA)患者、30例干燥综合征(SS)患者和40名正常人血清中的抗!2-GPⅠ抗体水平。同时,测定患者血清中的抗心磷脂抗体(ACL)等指标,并分析其与患者的临床特点(如:血栓、流产)的关系及其临床意义。统计学分析采用t检验、!2检验和Spearman检验。结果抗!2-GPⅠ抗体在SLE中敏感性为21.4%(24/112),特异性为88.6%,在RA和SS敏感性分别为15.0%(6/40)和6.7%(2/30),40名正常对照均为阴性。抗!2-GPⅠ抗体与血栓形成密切相关(P<0.01),与ACL-IgG和IgM型水平呈正相关(r=0.479,P=-0.032;r=0.400,P=0.045)。抗!2-GPⅠ抗体与其他临床及实验室指标无明显相关性。结论抗!2-GPⅠ抗体在SLE中具有一定的敏感性,且可能在SLE的血栓形成中发挥作用,联合检测ACL与抗!2-GPⅠ抗体能够辅助诊断SLE伴血栓形成。     

Anti-prothrombin antibodies combined with lupus anti-coagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus

Anti-prothrombin antibodies (anti-prothrombin) and anti-beta2-glycoprotein I antibodies (anti-beta2-GP I) are the most common and characterized anti-phospholipid antibodies (aPL) detected using specific enzyme-linked immunosorbent assay (ELISA) systems. Recently, lupus anti-coagulant (LA) activity detected by a phospholipid-dependent coagulation assay was reported to be associated with anti-prothrombin and/or anti-beta2-GP I. Here we show that the co-existence of IgG anti-prothrombin and LA activity might be an essential risk factor for venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE). We examined not only the levels of antibodies to prothrombin and anti-beta2-GP I (both IgG and IgM isotypes) using an ELISA system, but also LA activity detected using both diluted Russell's viper venom time (dRVVT) and STACLOT LA test in 124 patients with SLE. The SLE patients were divided into four groups according to the results of ELISA and LA assay results for each aPL: group A, ELISA+ and LA+ group B, ELISA+ and LA-; group C, ELISA- and LA+ group D, ELISA- and LA-. Regarding IgG anti-prothrombin, the prevalence of VTE was significantly higher in group A (16/35 cases, 45.7%, P < 0.001, Fisher's exact probability test) than in the other groups (B, 2/30, 6.7%; C, 1/22, 4.5%; D, 1/37, 2.7%). With respect to IgM anti-prothrombin and IgG or IgM anti-beta2-GP I, the prevalence of VTE was higher in both groups A and C than in group D, but no statistical difference in prevalence was found between groups A and C. Multivariate logistic regression analysis of risk factors for VTE confirmed that the co-existence of IgG anti-prothrombin and LA activity was the only significant risk factor for VTE (odds ratio, 19.13; 95% confidence intervals, 4.74-77.18).     

Antiendothelial cell antibodies in systemic lupus erythematosus

Objective: Anti‐endothelial cell antibodies (AECAs) are a heterogeneous group of antibodies against a variety of antigenic determinants on endothelial cells (EC). AECAs are known to play an immunopathogenic role in triggering EC activation, leading to vascular damage. The purpose of this study was to assess: (i) the incidence of AECAs in systemic lupus erythematosus (SLE) patients with nephritis (LN) and to compare this with SLE patients without clinical evidence of nephritis; and (ii) to understand the association of AECAs with disease severity based on renal histopathological findings. Method: Fifty‐three clinically and histopathologically proven cases of LN were studied along with 20 patients without evidence of nephritis. AECAs were detected by immunofluorescence using cultured human umbilical vein endothelial cells (HUVECs). The titres and immunoglobulin subclass of AECAs were also identified. Other autoantibodies were also detected. Results: In the LN group, 21 (39.6%) were AECA positive and 19 (35.8%) were antineutrophil cytoplasmic antibody (ANCA) positive. Autoantibodies to double‐stranded DNA (anti‐dsDNA) were present in 49 (92.4%) cases. In patients without nephritis, seven (35%) tested positive for AECA, five for ANCA and all were antinuclear antibody (ANA) positive. Anti‐dsDNA was detected in 16 patients (80%), higher incidence of AECAs was noted in diffuse proliferative glomerulonephritis (41.2%) as compared to focal proliferative glomerulonephritis (37.5%) and membranoproliferative glomerulonephritis (33.3%). IgG‐AECA subclass was noted in 85.7% patients, IgM‐AECA and IgG + M AECA subclasses of AECA were detected in 7.1% cases. AECAs were also found to be associated with other autoantibodies such as ANA, anti‐dsDNA and ANCA. Conclusion: No significant differences in AECA positivity was found between SLE with and without nephritis.     

系统性红斑狼疮脑病36例临床分析

目的研究系统性红斑狼疮脑病患者临床表现特点。方法分析、归纳2000-01-01~2004-10-10中日友好医院神经内科36例系统性红斑狼疮脑病患者症状、体征、辅助检查。结果36例系统性红斑狼疮脑病患者主诉症状9类,其中头痛、意识障碍、肢体无力居发生率前3位;发现体征13类,其中病理反射、意识障碍、肢体瘫痪居前3位。结论(1)系统性红斑狼疮脑病是活动性系统性红斑狼疮的表现之一。(2)系统性红斑狼疮患者无论病史长短,均可发生系统性红斑狼疮脑病。(3)系统性红斑狼疮脑病表现复杂多样。     

Endothelial cell-binding antibodies in patients with systemic lupus erythematosus

 The implications of endothelial cell-binding IgG antibodies (EC IgG) in systemic lupus erythematosus (SLE) was evaluated by determining level of EC IgG in sera from 112 SLE patients. The serum EC IgG level was determined by the cyto-ELISA method using human umbilical vein endothelial cells (HUVEC), human microvascular endothelial cells (HMVEC), and aortic endothelial cells (HAEC) as antigens. The levels of EC IgG were significantly higher among patients with SLE than among healthy control subjects (P < 0.001), and 68% (76/112) of SLE patients were shown to be EC IgG-positive. In patients with active lupus nephritis, the level of EC IgG was statistically and significantly elevated compared with those without lupus nephritis (P < 0.05). Negative correlations between EC IgG level and levels of CH50, C3, and lymphocyte count were revealed (P < 0.05, P < 0.005, and P < 0.05, respectively). When clinical course was evaluated, the levels of EC IgG correlated with disease activity. Definitive correlations in antibody levels between HUVEC and HMVEC, and between HUVEC and HAEC were revealed (both P < 0.0001). The results of this study revealed that the EC IgG in patients with SLE was involved in the onset of clinical manifestation, especially in patients with active lupus nephritis. Received: January 28, 2002 / Accepted: July 12, 2002 Acknowledgments This investigation was supported by grants from the Research Committee on Intractable Vasculitides, and the Ministry of Health and Welfare of Japan, from 1996 to 2000. Correspondence to:H. Bando     

A case of systemic lupus erythematosus with various central and peripheral neurological disorders developed with motor paralytic bladder as a major manifestation

A 29-year-old female with systemic lupus erythematosus who developed accerelated hypertension, motor paralytic bladder and various other neurological abnormalities is described. Cystometry demonstrated flaccid atonic neuropathic bladder. Elevated protein level and albuminocytologic dissociation were recognized in her cerebral spinal fluid. Magnetic resonance imaging study detected high signal intensities in themedulla oblongata andcauda equina. Her clinical symptoms and laboratory abnormalities were resolved after two courses of methyl-prednisolone pulse therapy. Possible roles of antiphospholipid antibodies were considered in the pathogenesis of her neurologic abnormalities.     

系统性红斑狼疮患者血栓性事件与血浆血小板来源的细胞外微囊泡水平的关联性

[目的]探讨血小板来源的细胞外微囊泡(PEV)与系统性红斑狼疮(SLE)血栓性事件的关联性。[方法]采用横断面研究方法,纳入2019年1月—2022年4月于开滦总医院风湿免疫科就诊的SLE患者144例。收集入选患者的一般情况、实验室数据以及血栓性事件资料,采用流式细胞术检测血浆PEV。比较合并和未合并血栓性事件的SLE患者之间血浆PEV水平,并进一步将144例SLE患者分为高水平PEV组(PEV≥300.48个/μL)和低水平PEV组(PEV<300.48个/μL),比较不同PEV水平组间血栓性事件发生情况和凝血指标间的差异,采用Spearman相关分析血浆PEV与凝血指标的相关性,多因素Logistic回归分析血浆PEV与血栓性事件的关联性。[结果]合并血栓性事件的SLE患者血浆PEV水平高于无血栓性事件的SLE患者[306.65(150.98,342.75)个/μL比227.04(178.23,281.36)个/μL,P<0.01]。与低水平PEV组比较,高水平PEV组血栓性事件发生率更高(38.29%比20.61%,P<0.05)。Spearman相关分析显示,...     

Clinical significance of plasma presepsin levels in patients with systemic lupus erythematosus

Objectives: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SLE.

Methods: This retrospective study comprised 35 patients with SLE and 72 with non-SLE autoimmune diseases who visited our facility during the period from August 2012 to September 2015. Plasma PSEP levels and laboratory data were compared between SLE and non-SLE. Clinical markers of SLE disease activity, including SLE disease activity index 2000 (SLEDAI-2K), serum complement concentrations and serum anti-ds-DNA antibodies were assessed in correlation with plasma PSEP levels.

Results: Plasma PSEP levels in SLE were higher than those in non-SLE. This phenomenon holds true when comparing SLE and non-SLE patients in the absence of infection (p?=?.0008). Plasma PSEP levels in SLE patients negatively correlated with C3 (r =?–0.4454, p =?.0430), CH50 (r =?–0.4502, p =?.0406) and positively with SLEDAI-2K (r =?0.4801, p =?.0237).

Conclusion: Elevated plasma PSEP levels were correlated with disease activity of SLE, suggesting inappropriate monocyte or neutrophil activation in the pathophysiology of SLE exacerbation.     

Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage

While it has been established that anti-phospholipid antibodies (aPL) are associated with recurrent miscarriage (RM), the importance of anti-beta2 glycoprotein 1 (GP1) IgG and anti-annexin V IgG antibodies as risk factors for RM is undefined. We have investigated the prevalence of anti-beta2 GP1 IgG and anti-annexin V IgG antibodies in 54 aPL-positive and 48 aPL-negative women with RM. The prevalence of IgG anti-beta2 GP1 antibodies was not significantly different in persistently aPL-positive women with RM (7%), aPL-negative women with RM (6%) and the normal parous control group (3%). Anti-annexin V IgG antibody prevalence was significantly increased in aPL-positive women with RM compared with aPL-negative women with RM (P = 0.01). The elevations were found in 35%, 19% and 16% of aPL-positive women with RM, aPL-negative women with RM and the control group respectively. No women showed positivity for both anti-beta2 GP1 IgG and anti-annexin V antibodies. Anti-beta2 GP1 IgG antibodies do not appear to be contributory to the investigation of women with RM. Anti-annexin V antibody positivity, although associated with aPL positivity in women with RM, is not an independent risk marker.     

Clinical and serological correlates of antinucleosome antibodies in South Africans with systemic lupus erythematosus

Antinucleosome antibodies (AnuA) are increasingly recognized as an important biomarker in the diagnosis and subset stratification of patients with systemic lupus erythematosus (SLE). The aim of the study was to determine the sensitivity, specificity, and clinico-serological correlates of AnuA in black South Africans with SLE. We performed a cross-sectional study of 86 SLE patients attending a tertiary center and 87 control subjects. AnuA were tested using a second-generation enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value of AnuA were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p < 0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were seropositive for AnuA were more likely to have skin involvement (discoid lupus and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our findings provide further evidence that AnuA are a sensitive and specific diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores suggest that AnuA may have a role in predicting disease outcome. The correlation between IgG aCL and AnuA is a novel finding that merits further studies to determine possible common peptide specificities of the antibodies.