外周血T淋巴细胞亚群、NK细胞与系统性红斑狼疮活动性的关系

目的探讨系统性红斑狼疮（SLE）患者外周血淋T淋巴细胞亚群与病情活动性、肾脏损害的关系。方法采用APAAP法对78例SLE患者T淋巴细胞亚群及NK细胞作检测，分析SLE活动情况、肾脏损害与细胞免疫学指标改变之间的关系。结果活动期组SLE患者与非活动期组相比。CD3^＋、CD8^＋细胞数显著降低（P〈0．05）．而CD4^＋细胞数、CD4^＋／CD8^＋比值无明显差异；伴有肾脏损伤患者，NK细胞数明显降低（P〈0．05）。而CD8^＋、CD3^＋、CD4^＋／CD8^＋比值无明显差异。结论SLE患者外周血CD3^＋、CD8^＋细胞数的降低与疾病的活动度有关。CD4^＋细胞及CD4^＋／CD8^＋比值不能反映其病情活动；而NK细胞数量的减少往往与肾脏损害有密切关系。     

Clinical utility of urinary soluble CD163 in evaluation of lupus nephritis patients

Aim of the workTo assess urinary soluble CD163 (sCD136) in systemic lupus erythematosus (SLE) patients compared to healthy controls. In addition to determine its association with different SLE clinical features, laboratory investigations and pathological indices focusing on those suggest renal disease activity.Patients and methodsThe study included 58 SLE patients and 30 controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active lupus nephritis (ALN) (renal SLEDAI ≥ 4) and no-renal activity (NRA) SLE patients (renal SLEDAI = 0). Urinary sCD163 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Urine values were normalized to urinary creatinine excretion. Renal biopsies were performed in 21 ALN patients.ResultsThey were 54 females and 4 males with a mean age 31.8 ± 9.1 years and disease duration 6.2 ± 4.8 years. They were 31 with ALN and 27 NRA SLE patients. Urinary sCD163 level was significantly higher in SLE patients (1.85 ± 0.3) than controls (0.5 ± 0.36, p < 0.001). In ALN, it was significantly higher (2.91 ± 2.52) compared to NRA SLE patients (0.64 ± 0.38) and controls (p < 0.001 in both). The optimum cut-off value above which normalized urinary sCD136 can predict renal activity was > 0.82 with sensitivity of 90.3%, specificity of 88.89%, p < 0.001. Urinary sCD163 significantly correlated with renal (r = 0.75, p < 0.001) but not with extra-renal SLEDAI. It correlated with activity index of renal biopsy (r = 0.46, p = 0.038).ConclusionUrinary sCD163 is a potential biomarker for LN activity. Its level is associated with clinical features, laboratory investigations and pathological indices that indicate renal disease activity.     

羟氯喹联合利妥昔单抗治疗系统性红斑狼疮的临床研究

目的 研究羟氯喹联合利妥昔单抗治疗系统性红斑狼疮的临床疗效。方法 选择2017年1月—2019年12月榆林市第二医院的系统性红斑狼疮患者71例作为研究对象。用抽签法随机将患者分为对照组（36例）和观察组（35例）。对照组iv利妥昔单抗注射液,100 mg/次,1次/周。观察组在对照组基础上口服硫酸羟氯喹片,0.4 g/次,2次/d。两组均治疗4周。观察两组患者的临床疗效,同时比较两组治疗前后的系统性红斑狼疮疾病活动指数（SLEDAI）评分、24 h尿蛋白、血肌酐、血清白蛋白和炎性因子水平。结果 治疗后,观察组的有效率为91.43%,明显高于对照组的69.44（P<0.05）。治疗后,两组的SLEDAI评分、血肌酐及24 h尿蛋白水平明显降低,血清白蛋白水平明显升高（P<0.05）;且观察组的SLEDAI评分、血肌酐及24 h尿蛋白水平明显低于对照组,血清白蛋白水平明显高于对照组（P<0.05）。治疗后,两组血清白细胞介素（IL）-4、IL-17和单核细胞趋化蛋白-4（MCP-4）水平明显降低（P<0.05）,且观察组的血清IL-4、IL-17和MCP-4水平明显低于对照组（P<0.05）。结论 羟氯喹联合利妥昔单抗能改善系统性红斑狼疮患者的免疫功能,降低血清IL-4、IL-17和MCP-4水平,具有一定的临床推广应用价值。     

The Tie2 Receptor Antagonist Angiopoietin-2 in Systemic Lupus Erythematosus: Its Correlation with Various Disease Activity Parameters

Background: Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage. Objective: to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity. Patients and methods: The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins. Results: The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p < 0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE. Conclusion: Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.     

B cell elimination in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus.     

The role of interleukins 4, 17 and interferon gamma as biomarkers in patients with Systemic Lupus Erythematosus and their correlation with disease activity

Aim of the workThis work was designed to study the production of proinflammatory cytokines in SLE patients and their correlation with disease activity and study if they can be used as biomarkers for renal activity in lupus nephritis patients.Patients and methodsThis study was carried out on 70 subjects divided into two groups: Group I (SLE group) which included 40 SLE patients and Group II (Control group) which included 30 apparently healthy controls. The patients were subjected to full history taking and complete clinical examination. Assessment of disease activity in SLE patients by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Sera of patients and controls were screened for the level of cytokine expression of T helper cells including interleukin 17 (IL-17), interleukin 4 (IL-4) and interferon gamma (IFN-γ).ResultsSerum levels of IL-4 were significantly lower while both IL-17 and IFN-γ were significantly higher in SLE patients than in the control group. The most powerful predictor and correlated cytokine with the SLEDAI in SLE patients was IL-17. Higher serum level of IFN-γ was associated with more pyuria and hematuria, while higher IL-17 was associated with more pyuria and proteinuria in SLE patients.ConclusionThe serum level of IL-17 and IFN-γ was proven to be significantly higher in SLE patients and can be used as biomarkers of renal activity.     

影响系统性红斑狼疮活动指数评分的主要指标分析

目的 探讨系统性红斑狼疮(SLE)住院患者的分布特征、临床表现、实验室指标及活动指标,为临床诊断提供更多的参考.方法 收集2006年1月至2010年6月宁夏医科大学总医院1037例SLE住院患者的病案资料.采用t检验和x2检验进行统计学分析.结果 5年住院病例呈逐年上升趋势;发病特点以20～40岁女性最为常见,占67.5％,男女比例为1∶8.26.关节痛是最常见的首发症状,占54.3％,其次是皮疹,占48.2％;补体C3下降、蛋白尿、血小板降低和抗dsDNA阳性可以作为SLE早期诊断的指标.综合分析SLE疾病活动指数(SLEDAI )＞9的患者占26.0％,影响SLEDAI活动指数评分的主要指标是:发热、关节痛、皮疹、蛋白尿、补体降低、抗dsDNA抗体滴度升高、胸膜炎、脱发、口腔溃疡、心包炎、活动性神经精神症状、血小板降低;活动组在发热、关节痛、皮疹、面部红斑、肺脏损害、脱发、口腔溃疡、心脏损害、神经精神症状和肾脏损害等的发生率均高于非活动组.抗dsDNA抗体滴度、红细胞沉降率和C3、C4水平异常发生率等指标在活动组均高于非活动组.结论 SLE是多系统、多脏器受累的疾病,在临床症状和免疫学指标上有其特征性改变,因而重视早期诊断,掌握疾病的发病特征和规律,正确判断病情的活动,对采取合理有效的治疗,延缓SLE患者病情发展,改善预后具有重要意义.     

High-sensitivity C-reactive protein (hs-CRP) in systemic lupus erythematosus patients without cardiac involvement; relation to disease activity,damage and intima-media thickness

Aim of the workTo assess the high sensitivity C-reactive protein (hs-CRP level) in systemic lupus erythematosus (SLE) patients without cardiac involvement and find its relation with clinical and laboratory findings, disease activity, damage index and intima-media thickness (IMT).Patients and methodsForty-five female SLE patients were recruited in the present study without any cardiac involvement. History taking, examination and laboratory investigations were performed for patients. Disease activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage by the Systemic Lupus International Collaborating Clinics (SLICC) index. Thirty age matched female healthy subjects were considered as a control group. hs-CRP was measured quantitatively by microplate immunoenzymometric assay and the IMT measured by ultrasonography.ResultsThe hs-CRP in the patients was significantly higher (4.84 ± 3.91 mg/l) compared to the control (1.74 ± 0.61 mg/l) (p < 0.001). The IMT in the patients was significantly increased (0.72 ± 0.37 mm) compared to the control (0.54 ± 0.15 mm) (p 0.004). There was no difference in the level of hs-CRP according to the presence or absence of clinical manifestations. However, it was significantly higher in those with positive DNA (5.71 ± 4.36 mg/L) compared to those with negative results (3.12 ± 1.97 mg/L) (p 0.009). There was a significant correlation of the hs-CRP level with the IMT (r 0.49, p 0.001) and SLEDAI (r 0.67, p < 0.001).ConclusionsThese findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of future cardiac events. Measuring hs-CRP may be useful as a marker of disease activity, increased IMT and subclinical atherosclerosis in SLE especially those with positive ds-DNA.     

CXCR3 polymorphism is associated with male gender and pleuritis in patients with systemic lupus erythematosus

Background

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organs. Chemokines and their receptors play an important role in the pathogenesis of SLE. Lymphocytes expressing CXCR3, chemokine receptors of CXCL4, 9, 10, and 11, increase in patients with SLE and animal models, particularly in those with skin manifestations and nephritis. We investigated CXCR3 genetic polymorphisms in patients with SLE and their association with clinical manifestations.

Methods

A total of 346 patients with SLE and 540 healthy controls were investigated for CXCR3 intron 1 polymorphisms rs2280964 and rs34334103 by Taqman analysis.

Results

rs2280964 and rs34334103 were not associated with all patients with SLE, but rs34334103 showed a significant association with male patients with SLE. Among the clinical manifestations, pleuritis was associated with the rs34334103 polymorphism.

Conclusion

The CXCR3 polymorphism rs34334103 was associated with male gender and pleuritis in patients with SLE.     

血清sFas和sICAM-1的测定对系统性红斑狼疮患者疾病活动性及治疗转归预测价值

目的:探讨系统性红斑狼疮(SLE)患者血清凋亡调节蛋白sFas和可溶性细胞间黏附分子(sICAM-1)对疾病活动性及治疗转归的预测价值.方法:采用酶联免疫吸附试验(ELISA)检测SLE患者和正常人血清sFas和sICAM-1的水平,分析sFas和sICAM-1的含量与SLE患者的疾病活动度指数SLEDAI和免疫指标(ANA、dsDNA等)的相关性,研究用sFas和sICAM-1指标判断疾病的活动性,并进行了SLE病例的前瞻性和治疗前后对照研究.结果:SLE患者血清sFas和sICAM-1平均水平分别为4.18μg/L和464.5μg/L,显著高于正常对照组2.27μg/L和190.4μg/L.SLE患者血清sFas和sICAM-1水平活动期均高于非活动期(P＜0.001),ANA高滴度组高于ANA低滴度组,dsDNA抗体阳性组高于dsDNA抗体阴性组,肾损害组高于非肾损害组;且SLE患者血清sFas和sICAM-1水平与SLE患者SLEDAI呈正相关(r=0.688和r=0.728).以非活动性SLE组的-x±s作为评判临界值,同时定量检测sFas(＞4.45 μg/L)、sICAM-1(＞438.6μg/L)对SLE活动性的预测具有较好的灵敏度、特异度.结论:sFas和sICAM-1与SLE发病有关,可反映SLE患者的疾病活动性,同时定量检测可有助于预测患者的病情活动和转归.