Th17 cells in rheumatoid arthritis and systemic lupus erythematosus

Recent work has implicated a novel Th effector cell subset, the Th17 cell subset, in the development of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) because of the ability of Th17 cells to produce cytokines like IL‐17 and IL‐21 that can drive both inflammatory and humoral responses. In this review, we will discuss recent studies that have begun elucidating the factors that regulate the development of Th17 cells and provide a brief overview of the role of Th17 cells in RA and SLE.     

Treatment adherence in patients with rheumatoid arthritis and systemic lupus erythematosus

This study assessed self-reported adherence in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) from underserved healthcare settings. We conducted a cross-sectional survey of 102 ethnically diverse patients--70 with RA and 32 with SLE--attending rheumatology clinics at publicly funded hospitals in Houston, Texas; 43% were Hispanic, 32% African-American, and 25% White. Treatment adherence was evaluated using the compliance questionnaire rheumatology (CQR; 0, low adherence and 100, high adherence) and the questionnaire of the Adult AIDS Clinical Trials Group (AACTG). The patients were also asked how often they forgot to take their prescribed medications or discontinued them on their own. Mean patient age was 48.5 years; 75% were female, 32% were African-American, 43% Hispanic, and 25% White. Only one third reported never forgetting to take their medications; 40% reported having stopped their medications on their own because of side effects, and 20% because of lack of efficacy. Mean CQR score was 69.1 +/- 10.5, suggesting moderate adherence overall. Differences were also observed across ethnic groups: 23% of ethnic minority patients had problems taking their medications at specified times compared to 11% of Whites (p = 0.03). Lower education and side effects were associated with lower adherence. No differences were observed between RA and SLE patients. Many patients with RA and SLE report problems with treatment adherence. These appear to be more prevalent in African Americans and Hispanics than Whites; the impact of decreased adherence on outcomes could be significant and should be considered when treating patients with RA and SLE.     

血管紧张素转化酶基因多态性与系统性红斑狼疮相关性研究

目的探讨位于人类17号染色体长臂2区3带(17q23)上的血管紧张素转化酶(ACE)基因多态性G261T与系统性红斑狼疮(SLE)的关系。方法采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)方法检测人类17q23上的ACE基因多态性G261T,运用家系为基础的相关性检验(FBAT)方法,对119个中国汉族SLE患者家系(其中核心家系95个,119例患者,316名家系其他成员)ACE多态性位点(rs4303)进行等位基因和基因型分析。结果在119例SLE患者中：G、T等位基凶频率分别是44．8%和55．2%：基因型GG、GT和TT的频率分别是13．9%,62．0%,24．1%。FBAT单位点分析显示G261T多态性与SLE显著相关：附加模型(Z=2．877．P=0．004),显性模型(Z=2．557,P=0．011)以及隐性模型(Z= 2．202,P=0．028)。传递不平衡检验(TDT)和同胞传递不平衡检验(STDT)显示其中ACE-261T等位基因由杂合子父母优势传递给患病子女或者与正常同胞相比更容易传递给患者(X~2=11．66,P=0．001)。结论ACE基因是中国汉族人群SLE的易感基因；其中ACE-261T等位基因与SLE发病相关。     

Oxidative stress in systemic lupus erythematosus and rheumatoid arthritis patients: relationship to disease manifestations and activity

Aim: The present work was undertaken to study the status and contribution of oxidative stress in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. Relationship of the markers of oxidative stress to clinical manifestations, disease activity, damage and medications used were well considered. Methods: Thirty SLE and 30 RA female patients were included in the study and clinical examination and investigations were performed and disease activity was assessed. Markers of oxidative stress, including malondialdehyde (MDA) and antioxidant scavengers with glutathione (GSH) and glutathione peroxidase (GSH Px) were assessed. Results: Level of MDA, GSH and GSH Px were remarkably altered in RA and SLE patients compared to controls. Markers of increased oxidative stress and impaired antioxidant capacity were profound in RA and significantly reflected disease activity in RA and SLE, with special attention to alopecia and lupus nephritis. RA patients receiving methotrexate had significantly altered parameters and the steroid dose in SLE patients correlated with these markers. Conclusion: Oxidative stress was increased and more profound in RA than SLE and could well reflect disease activity, with special attention to SLE patients with alopecia and nephritis. Medications used are closely related to the oxidant/antioxidant imbalance. Considering antioxidants in novel therapeutic strategies is important in SLE and RA patients.     

Increased circulating platelet–leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis

It is possible that platelet activation may play a pathogenic role in the increased risk of thrombosis associated with antiphospholipid antibodies (APA). In this study, levels of in vivo platelet activation were measured in 20 patients with primary antiphospholipid syndrome (PAPS) and 30 systemic lupus erythematosus (SLE) patients (14 of whom had secondary APS) using sensitive flow cytometry. Soluble P-selectin levels were also assayed. Platelet CD63 expression was significantly higher in PAPS than normal controls (P = 0.007), as well as SLE patients with and without secondary APS (P = 0.03 and P = 0.002 respectively). PAC-1 binding was significantly higher in PAPS than the control group (P = 0.007) and SLE patients without APS (P = 0.015). Platelet-leucocyte complexes were significantly higher in SLE patients than both PAPS and the control group, and platelet-monocyte complexes were significantly increased in PAPS compared with the control group. (Platelet-leucocyte complexes were also significantly higher than controls in 10 rheumatoid arthritis (RA) patients without APA). Soluble P-selectin levels were significantly higher in PAPS and SLE patients than the control group. Platelet CD62p expression, annexin V binding and platelet microparticle numbers were not increased in PAPS or SLE patients. We conclude that there is evidence of increased platelet activation in PAPS and SLE, and this is important to note as it may have potential therapeutic implications with respect to use of antiplatelet agents in these patients.     

The frequency of circulating immune complexes in rheumatoid arthritis and systemic lupus erythematosus

Summary Sera from patients with rheumatoid arthritis and systemic lupus erythematosus have been examined for the presence of complement-fixing immune complexes using three assays, (a) a fluid phase Clq binding assay, (b) a solid phase Clq binding assay and (c) the Raji cell assay.By simultaneously screening all the sera within each disease group we established that circulating immune complexes frequently occur but that there is a discordance between the assays, even between the two assays involving binding to Clq. Distinct clinical profiles emerged with the fluid phase Clq binding assay being most frequently positive in sera from patients with extra-articular rheumatoid arthritis. The solid phase Clq binding assay and the Raji cell assay were more frequently positive in sera from patients with systemic lupus erythematosus. The prevalence of circulating immune complexes and the comparative performance of the three assays in each disease is examined in detail.     

Leflunomide in the treatment of rheumatoid arthritis and other autoimmune disorders

Leflunomide (Arava) is an isoxazole derivative approved by the US Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis (RA). Its mechanism of action is based on the inhibition of dihydro‐orotate dehydrogenase, an enzyme that controls the pathway for denovo synthesis of uridine ribose monophosphate (rUMP) in activated T‐cells. Leflunomide is structurally unrelated to other known immunomodulatory drugs in clinical use. Data have demonstrated benefit in control of clinical symptoms and quality of life in RA and prevention of radiologic progression after 24 months of treatment. Further, studies suggest a role for the combination of methotrexate plus leflunomide in the treatment of some patients with refractory RA. Recent studies have also indicated efficacy in psoriatic arthritis, other autoimmune disorders and in prevention of allograft rejection. A recent important issue is reports of potentially serious liver toxicity and guidelines for monitoring toxicity.     

Septic arthritis in patients with systemic lupus erythematosus: salmonella and nonsalmonella infections compared

OBJECTIVES: To assess the clinical characteristics and outcome of systemic lupus erythematosus (SLE) with septic arthritis. METHODS: In this 20-year retrospective study, we reviewed the charts of SLE patients with septic arthritis confirmed by synovial fluid analysis and culture. To identify risk factors for septic arthritis, data of SLE patients with septic arthritis were compared with data of 100 hospitalized SLE patients without septic arthritis. RESULTS: There were 10,732 inpatient records of 3,127 SLE patients; 29 SLE patients had septic arthritis. Their ages ranged from 14 to 68 years (mean, 35.1 +/- 14.1 years). The mean SLE duration before septic arthritis onset was 30.6 months. All patients received corticosteroids; 93% had active disease (SLEDAI > or = 4). Compared with controls, avascular necrosis (AVN) of the femoral head was the most common predisposing articular disease (Odds ratio, 3.799;CI, 1.59 to 9.05). Of the 29 patients, 17 (59%) had salmonella infections and 12 (41%) had other infections. Salmonella-infected patients were younger (28.7 +/- 10.4 years) than those with nonsalmonella infections (44.1 +/- 14.0 years; P = 0.002). The hip was the most commonly affected joint, especially in the salmonella group, followed by the knees and ankles. Salmonella-infected patients were more prone to oligo-articular septic arthritis. The overall mortality rate was 10%. CONCLUSIONS: Salmonella enteritidis B is the most common pathogen causing septic arthritis in younger SLE patients. Septic arthritis tended to be oligo-articular and involve the hip joint. AVN of the femoral head was the most common predisposing articular disease. Once septic arthritis is suspected, culture specimens should be collected and appropriate antibiotics given immediately.     

Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis patients

Objectives

Rheological characteristics of blood are strongly linked to atherothrombosis in the general population, but its contribution to atherosclerosis in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is currently unclear. This work examines the relationship between blood rheology, traditional cardiovascular (CV) risk factors, inflammation and subclinical atherosclerosis in SLE and RA.

Methods

Whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte deformability (ED), aggregation (EA) and erythrocyte NO production were measured in 197 patients (96 SLE and 101 RA) and compared to 97 controls, all females without previous CV events. Clinical information was obtained and fasting lipids and acute phase reactants were measured. The relationship between hemorheological parameters, CV risk factors and inflammation was assessed in patients and the impact of these variables on carotid intima-media thickness (cIMT) was evaluated in univariate followed by multivariate regression analyses.

Results

WBV and ED are significantly lower in patients, while EA is elevated as compared with controls. Hemorheological disturbances correlate with CV risk factors and markers of inflammation and are more profound in patients with metabolic syndrome. Multivariable analysis showed that menopause (OR 34.72, 95%CI 4.44–271.77), obesity (OR 4.09, 95%CI 1.00–16.68) and WBV (OR 3.98; 95%CI 1.23–12.83) are positively associated whereas current corticosteroid dose (OR 0.87; 95%CI 0.78–0.98), and erythrocyte NO production (OR 0.16; 95%CI 0.05–0.52) are negatively associated with cIMT.

Conclusion

Disturbed hemorheological parameters in SLE and RA women are related to the presence of CV risk factors and inflammation. WBV and erythrocyte NO are independently associated with the early stages of atherosclerosis.     

系统性红斑狼疮候选基因OAZ中单核苷酸多态性的系统筛选及相关分析

目的研究OLFl／EBF相关锌指蛋白基因（OAZ）上的单核苷酸多态性（SNP）与中国人群系统性红斑狼疮（SLE）发病的相关性。方法利用243个中国SLE患者核心家系DNA．依据http：／／www．hapmap．org/数据库中的信息，选取了OAZ基因上的35个SNP位点进行等位基因分型，以Haploview、Genehunter和Fbat生物信息学软件分析其与中国人SLE发病的相关性。结果对等位基因分型结果进行家系传递不平衡检验（TDT），提示rsl420683，rs6500240显示传递不平衡，rsl420683等位基因G优势传递给患者，传递：不传递=86：50，P=0．002；rs6500240等位基因C优势传递给患者，传递：不传递=88：56，P=0．008。结论OAZ基因上的SNP位点rs1420683和rs6500240与SLE发病相关．未发现这两个位点的突变影响转录因子的结合，并且相互之间并没有存在强的连锁关系，可能与邻近的某个影响蛋白结构或表达的功能性SNP存在连锁不平衡，需要进一步研究证实。     

Single nucleotide polymorphisms of CD244 gene predispose to renal and neuropsychiatric manifestations with systemic lupus erythematosus

Abstract

The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) of the CD244 gene with several clinical features of systemic lupus erythematosus (SLE). Two hundred and forty-three patients with SLE and 369 healthy controls were enrolled. Two SNPs (rs6682654 and rs3766379) in the CD244 gene were determined by allelic discrimination using a specific TaqMan probe. Only SNP rs3766379 was significantly associated with susceptibility to SLE [P = 0.009; odds ratio (OR) 1.28; 95% confidence interval (CI) 1.04–1.57]. The association was preferentially observed in subsets of SLE patients with nephritis and neuropsychiatric lupus. The frequency of the rs6682654 C allele was strongly associated with nephritis and neuropsychiatric lupus (P = 0.00065; OR 1.99; 95% CI 1.34–2.95, and P = 1.6 × 10^?7; OR 3.47; 95% CI 2.12–5.70, respectively), as was the frequency of the rs3766379 T allele (P = 0.0014; OR 1.86; 95% CI 1.27–2.71, and P = 2.6 × 10^?7; OR 3.15; 95% CI 2.00–4.96, respectively). In this study, an SNP of the CD244 gene was associated with susceptibility to SLE. There was a strikingly strong association in SLE patients with nephritis and neuropsychiatric lupus, suggesting that this genetic marker could predict involvement of those severe complications.     

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.