Treatment of Patients with Systemic Lupus Erythematosus including Nephritis with Chlorambucil

Six female patients with systemic lupus erythematosus (S.L.E.) have been treated with chlorambucil. In five the decision was taken after failure by corticosteroids to control progressive renal disease in the face of unacceptable corticosteroid toxicity. After the introduction of chlorambucil renal function improved and all patients remain well six, six, five, three, and two-and-a-half years later, respectively. On renal biopsy five had focal proliferative glomerulonephritis. Repeat biopsy in two cases showed quantitative improvement. The sixth patient was treated with chlorambucil because of failure by corticosteroids to control peripheral vascular lesions and haemolysis and she remains well four years later. In four patients is it probable that amenorrhoea was related to chlorambucil treatment, but there were no other important side effects although one patient developed a degree of marrow depression during treatment. Chlorambucil may hold advantages over the immunosuppressive drugs normally recommended in this condition, azathioprine and cyclophosphamide, as it appears less liable to cause important marrow suppression and, unlike cyclophosphamide is not associated with alopecia and haemorrhagic cystitis.     

系统性红斑狼疮病人的临床护理及出院指导

目的:探讨系统性红斑狼疮患者的护理经验。方法:回顾性分析45例系统性红斑狼疮患者临床及护理资料;在护理过程中采用心理护理、对症处理及出院指导等护理措施,强调加强心理护理和健康教育指导,根据不同年龄、不同性格、不同文化和社会背景,分别给予耐心解释和心理疏导。结果:改变了病人的心理状态和认知能力,使病人保持平和心态,树立坚持长期治疗,战胜疾病的信心。45例病人中除3例因经济问题放弃治疗,其余患者均达到临床缓解。经定期复查,70%的病人得到长期缓解。结论:本组病例采取的护理措施切实可行,行之有效。     

系统性红斑狼疮合并甲状腺功能减退症50例临床分析

目的:分析系统性红斑狼疮合并甲状腺功能减退症50例临床症状和治疗效果.方法:选取2010年6月至2012年6月间于我院接受诊断和治疗的系统性红斑狼疮合并甲状腺功能减退症患者50例作为观察组,同时选取同期入院的单纯系统性红斑狼疮患者50例作为对照组,分析两组临床症状的差异.观察组患者分别给予系统性红斑狼疮合并甲状腺功能减退症联合治疗和甲状腺功能减退症单独治疗,观察比较治疗前后甲状腺功能差异.结果:观察组患者关节病变发病率为64.00％明显高于对照组的22.00％(P＜0.05):观察组患者雷诺现象的发病率为36.00％明显高于对照组的6％(P＜0.05).联合治疗患者治疗后促甲状腺素水平明显低于单独治疗(P＜0.05),联合治疗患者治疗后游离甲状腺素和游离甲状腺三碘原氨酸水平均明显高于单独治疗(p＜0.05).结论:系统性红斑狼疮合并甲状腺功能减退症患者的关节病变和雷诺现象发病率明显较高,联合治疗后甲状腺功能减退症恢复较佳.     

血β2微球蛋白水平在系统性红斑狼疮中的临床意义

目的：探讨系统性红斑狼疮（systemic lupus erythematosus,SLE）患者血β2-MG水平与疾病活动的相关性及其临床意义。方法：随机抽取2012年2月-2012年7月我科收治的62例SLE患者（SLE组）和同期在我院门诊体检的健康体检者40例（对照组）,检测和比较两组血清β2-MG、自身抗体、补体水平,并对SLE患者进行SLEDAI评分,分析SLE患者血清β2-MG水平与自身抗体、补体水平和SLEDAI评分的相关性。结果：SLE组血β2-MG水平（3．11±0．40μg／mL）显著高于对照组（2．23±0．23μg/mL）,差异有统计学意义（P〈0．05）;其中发生口腔溃疡、浆膜炎及蛋白尿的SLE患者的血β2-MG水平与无此三种表现的患者相比显著升高,差异有统计学意义（P〈0．05）。SLE患者的血β2-MG水平与抗ds—DAN抗体、SLEDAI均呈显著正相关（分别为r=0．289,r=0．361,P〈0．01）,与C3呈负相关（r=-0．271,P〈0．05）。结论：SLE患者血β2-MG水平高于正常,可作为SLE疾病活动指标用于监测疾病活动。     

系统性红斑狼疮伴发急腹症的诊治思考 一附18 例临床分析

目的：提高对系统性红疯狼疮（SLE）伴发急腹症临床表现的认识,总结诊断和治疗此类病例的经验。方法：对18例SLE伴发急腹症的病例进行回顾性分析。结果：SLE并发急腹症临床表现多样化,可以表现为消化道出血,肠梗阻。肠穿孔,急性胃肠炎,急性胰腺炎,急性腹膜炎等。治疗后16例病情得到控制,2例死亡。结论：SLE伴发急腹症预示病情危重,对此应提高认识,尽早诊断;应用大剂量肾上腺皮质激素和免疫抑制剂有良好的疗效。     

水痘-带状疱疹病毒对系统性红斑狼疮患者体液免疫功能的影响

目的:观察水痘患者、系统性红斑狼疮(systemic lupus erythematosus,SLE)患者和系统性红斑狼疮合并水痘患者体液免疫指标的变化,探讨水痘-带状疱疹病毒对系统性红斑狼疮患者体液免疫功能的影响。方法:选择在我院诊断治疗的水痘患者、系统性红斑狼疮患者和系统性红斑狼疮合并水痘患者共66例,同时设21例正常对照组;利用血液细胞分析仪检测各组血液中白细胞计数(WBC)、血小板计数(PLT)以及血红蛋白含量(HGB);采用免疫比浊法检测各组血清中免疫球蛋白G(IgG)、免疫球蛋白A(IgA)和免疫球蛋白M(IgM)以及补体C3、C4的水平。结果:与正常对照组比较,水痘组、SLE组以及SLE合并水痘组WBC、PLT和HGB含量下降,其中SLE组和SLE合并水痘组WBC、PLT降低,差异有统计学意义(P<0.05或P<0.01);水痘组血清中IgG、IgA和IgM含量下降,SLE组和SLE合并水痘组血清中IgG、IgA和IgM含量上升,其中水痘组血清中IgA含量减少有统计学意义(P<0.05),SLE组和SLE合并水痘组血清中IgG、IgA含量增加有统计学意义(P<0.05或P<0.01);水痘组血清中补体C3、C4含量增加,SLE组和SLE合并水痘组血清中补体C3、C4含量减少,其中SLE合并水痘组减少且差异有统计学意义(P<0.05)。与SLE组比较,SLE合并水痘组WBC明显增加(P<0.05),血清中IgG、IgA和补体C3、C4降低且差异有统计学意义(P<0.05)。结论:水痘-带状疱疹病毒可引起系统性红斑狼疮患者免疫系统相关指标的改变并对其产生影响。     

环磷酰胺联合人免疫球蛋白治疗SLE 的临床疗效及对血清IL-4 及MCP-4 水平的影响

目的:探讨环磷酰胺联合人免疫球蛋白治疗系统性红斑狼疮的临床疗效及对血清白细胞介素-4(IL-4)及单核细胞趋化蛋白4(MCP-4)水平的影响。方法:选取我院2013年1月到2014年5月收治的76例系统性红斑狼疮患者进行研究,随机分为观察组和对照组各38例。对照组使用环磷酰胺联合强的松的治疗,观察组采用人免疫球蛋白、环磷酰胺及强的松联合治疗,应用系统性红斑狼疮疾病活动度评分(SLEDAI)评价疾病程度,记录治疗前后两组24h尿蛋白、血清IL-4及MCP-4水平,并观察不良反应发生率。结果:治疗后两组SLEDAI评分、24h尿蛋白及血清IL-4及MCP-4水平较治疗前均显著降低(P0.05),且观察组均显著低于对照组(P0.05)。观察组不良反应发生率显著低于对照组(P0.05)。结论:环磷酰胺联合人免疫球蛋白治疗系统性红斑狼疮的效果显著,有效降低了患者血清IL-4及MCP-4的水平,对患者的预后有积极的影响。     

系统性红斑狼疮患者血清中IL-17 的检测及临床意义

目的:通过检测系统性红斑狼疮(SLE)患者外周血中IL-17的水平,探讨其临床意义。方法:用酶联免疫吸附法(enzymelinked immunosorbent assay,ELISA)检测61例SLE患者及30例健康人血清IL-17水平,并收集整理SLE患者的临床资料及实验室数据,分析其与临床的关系。结果:活动期SLE患者血清IL-17水平明显高于正常对照组(P<0.01),与SLE非活动组相比,差异亦有统计学意义(P<0.01)。但SLE非活动组与正常对照组间无统计学意义。结论:IL-17水平在活动期SLE患者血清中表达明显增高,且与SLEDAI评分呈正相关,提示IL-17可能参与了SLE疾病的病理过程,可能与疾病活动的关系密切。     

护理干预对系统性红斑狼疮患者激素治疗依从性的影响

目的:探讨护理干预对系统性红斑狼疮患者激素治疗依从性的影响。方法:选取应用糖皮质激素治疗系统性红斑狼疮的患者104例为研究对象,随机分为对照组和研究组各52例。对对照组患者应用常规的护理模式,而对研究组患者进行全程护理干预。根据患者对药物依从性的差异进行有针对性的护理。研究结果采用x2检验和t检验对结果进行分析,当P0.05有统计学意义。结果:研究组进行护理干预后,患者治疗的依从性及临床效果均明显高于对照组,并且研究组对相关知识的掌握情况明显高于对照组。结论:护理干预可提高患者对健康知识的认知及激素治疗的依从性,增强治疗效果、降低并发症的发生,从而提升患者的生活质量。     

系统性红斑狼疮早发动脉粥样硬化的研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是累及多系统多器官的自身免疫病,近年来的流行病学研究发现SLE患者已成为心血管痰病(cardiovascular disease,CVD)的高危人群,早发动脉粥样硬化(atherosclerosis,AS)是SLE患者最常见的CVD之一.传统心血管危险因素如高血压、高脂血症、肥胖等不能完全解释SLE早发AS,非传统危险因素如自身抗体、免疫复舍物、内皮功能障碍、系统性炎症反应等在SLE早发AS的发病机制中的作用越来越受到关注,深入研究这些非传统危险因素在SLE早发AS的致病作用,将有助于防治SLE患者的CVD,提高SLE患者生存率.     

Cyclophosphamide in Treatment of Systemic Lupus Erythematosus: 7 Years' Experience

This paper describes our experience with cyclophosphamide in the treatment of systemic lupus erythematosus. Since 1965 42 such patients have been treated either singly with cyclophosphamide or in combination with steroid. Serious complications have been rare except for amenorrhoea, which occurred in 14 out of 32 patients within the reproductive period. Our experience suggests that cyclophosphamide has an important, though not primary, part to play in the therapy of this disease.     

Impact of Anti-Peroxynitrite-Damaged-Thymidine- Monophosphate Antibodies on Disease Activity in Patients with Systemic Lupus Erythematosus

Present study probes the role of peroxynitrite (ONOO^-)-modified thymidine-5′-monophosphate (TMP) in SLE patients with different disease activity scores according to the SLE Disease Activity Index (SLEDAI). Serum analysis showed significant increased number of subjects positive for anti-ONOO^--TMP-protein antibodies in SLE patients with different SLEDAI scores. Interestingly, the levels of these antibodies were significantly higher among SLE patients, whose SLEDAI scores were ≥20. In addition, a significant correlation was observed between the levels of anti-ONOO^--TMP-protein antibodies and the SLEDAI score (r = 0.595, p < 0.0001). In short, this study shows a positive association between anti-ONOO^--TMP-protein antibodies and SLEDAI. The stronger response observed in patients with higher SLEDAI scores suggests that anti-ONOO^--TMP-protein antibodies may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.     

Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

Systemic Lupus Erythematosus (SLE) is one of the most relevant world-wide autoimmune disorders. The formation of autoantibodies and the deposition of antibody-containing immune complexes in blood vessels throughout the body is the main pathogenic mechanism of SLE leading to heterogeneous clinical manifestations and target tissue damage. The complexity of etiology and pathogenesis in SLE, enclosing genetic and environmental factors, apparently is one of the greatest challenges for both researchers and clinicians. Strong indications for a genetic background in SLE come from studies in families as well as in monozygotic and dizygotic twins, discovering several SLE-associated loci and genes (e.g. IRF5, PTPN22, CTLA4, STAT4 and BANK1). As SLE has a complex genetic background, none of these genes is likely to be entirely responsible for triggering autoimmune response in SLE even if they disclosure a potentially novel molecular mechanisms in the pathogenesis'' disease. The clinical manifestations and disease severity varies greatly among patients, thus several studies try to associate clinical heterogeneity and prognosis with specific genetic polymorphisms in SLE associated genes. The continue effort to describe new predisposing or modulating genes in SLE is justified by the limited knowledge about the pathogenesis, assorted clinical manifestation and the possible prevention strategies. In this review we describe newly discovered, as well as the most studied genes associated to SLE susceptibility, and relate them to clinical manifestations of the disease.     

Molecular Characterization of Circulating Plasma Cells in Patients with Active Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC). The molecular characteristics and nature of circulating PC and B cells in SLE have not been completely characterized. Microarray analysis of gene expression was used to characterize circulating PC in subjects with active SLE. Flow cytometry was used to sort PC and comparator B cell populations from active SLE blood, normal blood and normal tonsil. The gene expression profiles of the sorted B cell populations were then compared.SLE PC exhibited a similar gene expression signature as tonsil PC. The differences in gene expression between SLE PC and normal tonsil PC and tonsil plasmablasts (PB) suggest a mature Ig secreting cell phenotype in the former population. Despite this, SLE PC differed in expression of about half the genes from previously published gene expression profiles of normal bone marrow PC, indicating that these cells had not achieved a fully mature status. Abnormal expression of several genes, including CXCR4 and S1P₁, suggests a mechanism for the persistence of SLE PC in the circulation. All SLE B cell populations revealed an interferon (IFN) gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells. These data indicate that SLE PC are a unique population of Ig secreting cells with a gene expression profile indicative of a mature, but not fully differentiated phenotype.     

The Impact of Vitamin D on Dendritic Cell Function in Patients with Systemic Lupus Erythematosus

Background

Excessive activity of dendritic cells (DCs) is postulated as a central disease mechanism in Systemic Lupus Erythematosus (SLE). Vitamin D is known to reduce responsiveness of healthy donor DCs to the stimulatory effects of Type I IFN. As vitamin D deficiency is reportedly common in SLE, we hypothesized that vitamin D might play a regulatory role in the IFNα amplification loop in SLE. Our goals were to investigate the relationship between vitamin D levels and disease activity in SLE patients and to investigate the effects of vitamin D on DC activation and expression of IFNα-regulated genes in vitro.

Methodology/Principal Findings

In this study, 25-OH vitamin D (25-D) levels were measured in 198 consecutively recruited SLE patients. Respectively, 29.3% and 11.8% of African American and Hispanic SLE patient had 25-D levels <10 ng/ml. The degree of vitamin D deficiency correlated inversely with disease activity; R = −.234, p = .002. In 19 SLE patients stratified by 25-D levels, there were no differences between circulating DC number and phenotype. Monocyte-derived DCs (MDDCs) of SLE patients were normally responsive to the regulatory effects of vitamin D in vitro as evidenced by decreased activation in response to LPS stimulation in the presence of 1,25-D. Additionally, vitamin D conditioning reduced expression of IFNα-regulated genes by healthy donor and SLE MDDCs in response to factors in activating SLE plasma.

Conclusions/Significance

We report on severe 25-D deficiency in a substantial percentage of SLE patients tested and demonstrate an inverse correlation with disease activity. Our results suggest that vitamin D supplementation will contribute to restoring immune homeostasis in SLE patients through its inhibitory effects on DC maturation and activation. We are encouraged to support the importance of adequate vitamin D supplementation and the need for a clinical trial to assess whether vitamin D supplementation affects IFNα activity in vivo and, most importantly, improves clinical outcome.     

成年女性系统性红斑狼疮血清中抗黄体抗体与月经异常 的相关性研究

目的:探讨成年女性系统性红斑狼疮(SLE)血清中抗黄体抗体与月经异常的相关性。方法:收集SLE患者及正常对照者的临床资料,详细记录入选研究对象的月经及生育情况,同时记录抗核抗体(ANA)等自身抗体的测定结果。采用酶联免疫吸附试验(ELISA)法检测患者血清中抗黄体抗体。结果:在入选的69例成年女性SLE患者中,26(38%)例患者抗黄体抗体阳性。而在40例健康对照者中,仅2(5%)例出现抗黄体抗体阳性。在入选的69例SLE患者中,29(42%)例患者的月经正常,40(58%)例患者出现月经异常。在40例健康对照者中,31(78%)例患者的月经正常,仅9(21%)例患者出现月经异常。有月经异常的SLE患者中抗黄体抗体的阳性率显著高于无月经异常的SLE患者(66%vs 18%,P<0.01),而在健康对照者中则未见有显著性差异。结论:SLE患者中抗黄体抗体的阳性率为38%,并可能与SLE的月经异常相关。     

Recent Developments in the Role of High-Mobility Group Box 1 in Systemic Lupus Erythematosus

High-mobility group box 1 (HMGB1) is an important molecule for several nuclear processes. Recently, HMGB1 has gained much attention as a damage-associated molecular pattern (DAMP) and has been implicated in the pathogenesis of several (auto)-immune diseases, in particular, systemic lupus erythematosus (SLE). A main pathogenic feature in SLE is the accumulation of apoptotic cells. Since HMGB1 is released from apoptotic cells it has been hypothesized that HMGB1 might fuel the inflammatory processes, as seen in this disease, and play a fundamental role in the pathogenesis. In this review, we discuss evidence in support of the theory that HMGB1 is an important mediator in SLE and may be considered a new autoantigen.     

Patients with Systemic Lupus Erythematosus Have Higher Prevalence of Thyroid Autoantibodies: A Systematic Review and Meta-Analysis

Background

Thyroid autoimmunity is considered the most common type of organ-specific autoimmune disorder and can be associated with other autoimmune endocrine disorders or non-endocrine diseases. Systemic lupus erythematosus is a prototypical autoimmune disorder with multifactorial etiology. The pathogenesis and development of the disease may result from a loss of immune tolerance and the resulting synthesis of autoantibodies against nuclear antigens. Autoimmune factors may be common features of both thyroid autoimmunity and systemic lupus erythematosus, making it likely that both conditions may coexist within some patients.

Methods and Findings

A number of studies have investigated whether an association between thyroid autoimmunity and systemic lupus erythematosus exists. However, the results of these studies have been inconsistent. Furthermore, most of these studies have had relatively small sample sizes, which have rendered them insufficiently powerful to determine whether there is an association between systemic lupus erythematosus and thyroid autoimmunity. The main objective of this meta-analysis is to provide reliable estimates of the extent of any association between thyroid autoimmunity and systemic lupus erythematosus by combining the primary data from all relevant studies. Literature databases were searched, including the Medline, Embase, Web of Science, Chinese Wanfang and CBM databases, from January 1970 to May 2014. A total of 1076 systemic lupus erythematosus cases and 1661 healthy controls were included in this study. From these data, the odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis results showed that the prevalence of thyroid autoantibody positivity in patients with systemic lupus erythematosus was higher than in healthy controls (TgAb: OR = 2.99, 95% CI = 1.83–4.89; TPOAb: OR = 2.20, 95% CI = 1.27–3.82, respectively).

Conclusion

The results of this meta-analysis suggest that thyroid autoimmunity is more prevalent in patients with systemic lupus erythematosus than in a control group.     

The Clinical Significance of Vitamin D in Systemic Lupus Erythematosus: A Systematic Review

Background

Vitamin D deficiency is more prevalent among SLE patients than the general population. Over the past decade, many studies across the globe have been carried out to investigate the role of vitamin D in SLE from various clinical angles. Therefore, the aim of this systematic review is to summarise and evaluate the evidence from the published literature; focusing on the clinical significance of vitamin D in SLE.

Methods

The following databases were searched: MEDLINE, Scopus, Web of Knowledge and CINAHL, using the terms “lupus”, “systemic lupus erythematosus”, “SLE and “vitamin D”. We included only adult human studies published in the English language between 2000 and 2012.The reference lists of included studies were thoroughly reviewed in search for other relevant studies.

Results

A total of 22 studies met the selection criteria. The majority of the studies were observational (95.5%) and cross sectional (90.9%). Out of the 15 studies which looked into the association between vitamin D and SLE disease activity, 10 studies (including the 3 largest studies in this series) revealed a statistically significant inverse relationship. For disease damage, on the other hand, 5 out of 6 studies failed to demonstrate any association with vitamin D levels. Cardiovascular risk factors such as insulin resistance, hypertension and hypercholesterolaemia were related to vitamin D deficiency, according to 3 of the studies.

Conclusion

There is convincing evidence to support the association between vitamin D levels and SLE disease activity. There is paucity of data in other clinical aspects to make firm conclusions.     

Establishment of Autoantibody-Producing Cell Lines from Peripheral Blood Lymphocytes of Patients with Systemic Lupus Erythematosus

Autoantibody-producing B cell lines were established from peripheral blood lymphocytes of patients with systemic lupus erythematosus. Peripheral blood lymphocytes obtained from five of seven patients were successfully transformed by Epstein-Barr virus. Two of four established B lymphoblastoid cell lines examined in this study produced anti-nuclear factor antibodies and one of them produced anti-single-stranded DNA and anti-double-stranded DNA antibodies. These results indicate that B cell clones committed to self antigens are transformed by Epstein-Barr virus and continue to produce autoantibodies. In order to establish a monoclonal autoantibody-producing B cell line, the cells were cloned by a limiting dilution method. The data suggest that it is possible to establish a monoclonal autoantibody-producing B cell line by the combination of transformation of B cells by Epstein-Barr virus and extensive cloning.