Histone H1/MBP hydrolysing antibodies - novel potential marker in diagnosis of disease severity in systematic lupus erythematosus patients

Recently we have shown the presence of catalytically active IgGs, capable to cleave histone H1 and bovine myelin basic protein (MBP), in blood serum of SLE patients. Here we present data that demonstrate the correlation between a) proteolytic activity towards histone H1 and MBP of IgG-antibodies from blood serum of SLE patients and b) disease severity level in these patients. IgGs were isolated from blood serum by chromatography on protein G-sepharose. Commercial preparations of bovine myelin basic proteins (MBP) and calf thymus histone H1 were used as substrates. Analysis of the proteolytic activity showed that 16 of 38 lgG-preparations (42,1%) obtained from blood serum of SLE patients were capable of cleaving both histone H1 and MBP with different efficiency. It was revealed that the presence in blood serum of lgGs possessing proteolytic activity towards both histone H1 and bMBP closely correlates with manifestation of the disease severity in SLE patients.

Ankle-Brachial Index in Systemic Lupus Erythematosus:A Senegalese Case-Control Study

Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis and increasing cardiovascular risk which is recognized as a major cause of morbidity and death. Whether subclinical atherosclerosis has been evaluated by several methods, there are very limited data about Ankle-Brachial Index (ABI) in patients with systemic lupus erythematosus. The aim of the present study was to compare this index, between SLE patients and controls. We conducted a case-control study in the Department of Internal Medicine of our institution during the period from August 1, 2017 to December 31, 2018. We included 100 subjects, including 50 SLE patients and 50 control cases. This included 44 women and 6 men in patients with an identical distribution in controls. The mean age was 33.5 ± 11.3 years for cases and 33.3 ± 11.3 years (p-value: 0.93) for controls subjects. There was higher frequency of cardiovascular risk factors such as dyslipidemia (p-value at 0.009), low level of serum HDL-cholesterol (p-value??0.001), hypertriglyceridemia (p-value at 0.000) and hyperuricemia (p-value at 0.000) in patients with SLE. Overweight/obesity was higher in controls subjects (p-value at 0.028). There was no statistically significant difference in the frequency of diabetes-mellitus, smoking and high blood pressure. The abnormally ABI was recorded in 19 patients with SLE (38%) and 8 controls (16%) with a p-value: 0.01 and odds ratio: 3.22. Eight patients (16%) and four controls (8%) had low ABI without significant difference (p-value: 0.11 but odds-ratio at 2.98). Eleven patients with SLE (22%) and five controls (10%) had high ABI (p-value: 0.05 and odds-ratio: 3.24). In patients with SLE only disease activity (cSLEDAI) at the inclusion of the study was correlated?to abnormal ABI.?Conclusion:?This study showed an increasing prevalence of abnormal ABI in black African patients with SLE compared to controls with a correlation between disease activity and abnormal ABI.

Effective immune-inflammation index for ulcerative colitis and activity assessments

BACKGROUND The inverse association between systemic immune-inammation index(SII)and overall survival in tumors has been studied.AIM To evaluate the hematological indexes for assessing the activity of ulcerative colitis(UC).METHODS In this case-control study,172 UC patients and healthy participants were included.Comparisons were made among groups of white blood cells,hemoglobin,platelets,neutrophils,lymphocytes,monocytes,SII,neutrophil-tolymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).The relationship with hematological inflammation was verified by Spearman correlation analyses.The efficiency of SII,NLR,and PLR for distinguishing between UC and severe disease status was assessed by the receiver operator curve and logistic regression analyses.RESULTS The values of SII,NLR,and PLR were higher in UC patients than in controls(P<0.001)and were positively correlated with the Mayo endoscopic score,extent,Degree of Ulcerative Colitis Burden of Luminal Inflammation(DUBLIN)score,and Ulcerative Colitis Endoscopic Index of Severity(UCEIS).The cut-off NLR value of 562.22 predicted UC with a sensitivity of 79.65%and a specificity of 76.16%.Logistic regression analysis revealed that patients with SII and NLR levels above the median had a significantly higher risk of UC(P<0.05).Risk factors independently associated with DUBLIN≥3 included SII≥1776.80[odds ratio(OR)=11.53,P=0.027]and NLR value of 2.67-4.23(OR=2.96,P=0.047)on multivariate analysis.Compared with the first quartile,SII≥1776.80 was an independent predictor of UCEIS≥5(OR=18.46,P=0.012).CONCLUSION SII has a certain value in confirming UC and identifying its activity.

Serum lipoprotein-associated phospholipase A2 activity in Chinese patients with systemic lupus erythematosus

Background:Few studies have explored the association between lipoprotein-associated phospholipase A2(Lp-PLA2)and systemic lupus erythematosus(SLE).However,most of these studies have investigated only European patient populations and have come to contradictory conclusions.Furthermore,few studies have been conducted on Chinese patient groups.This study aimed to explore the association between serum Lp-PLA2 activity and SLE in a Chinese patient group.Methods:Serum Lp-PLA2 activity was detected in 154 SLE patients and 55 age-,sex-,and body mass index-matched healthy controls.Information con-cerning the anthropometric data,clinical manifestations,SLE Disease Activity Index 2000(SLEDAI-2K),complement C3(C3),and complement C4(C4)erythrocyte sedimentation rate(ESR),and autoantibodies were evaluated.Results:The average level of serum Lp-PLA2 activity was 221�56 U/L in SLE patients compared with 160�37 U/L in healthy controls(p<0.001).SLE pa-tients that presented with nephritis,anemia,and fibrinolytic abnormality had higher serum Lp-PLA2 activity than SLE patients who did not present with these symptoms(p<0.05),and the levels of serum Lp-PLA2 activity correlated with the severity of the clinical manifestations(p<0.001).There was no correlation between serum Lp-PLA2 activity and serum autoantibodies levels(p>0.05).According to Spearman’s rank correlation coefficient,ESR,SLEDAI-2K,C3,and C4 significantly correlated with serum Lp-PLA2 activity(p<0.001).According to binary logistic regression,Lp-PLA2 activity was independently associated with active SLE in patients(OR 1.049;95%CI:1.025-1.073,p<0.001).Conclusions:Serum Lp-PLA2 activity is associated with some clinical man-ifestations(nephritis,anemia,and fibrinolytic abnormality)in SLE patients,and its activity may contribute to the development of SLE disease.These findings provide new insight into the pathogenesis of SLE.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Phenotypic characterization of patients with activated PI3Kδ syndrome 1 presenting with features of systemic lupus erythematosus

Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with APDS1.In this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)phenotype.The clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of SLE.The immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch recombination.These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE.Meanwhile,we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1.The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE phenotype.The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy.Here,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.

Relationship Between Clinical and Immunological Features with Magnetic Resonance Imaging Abnormalities in Female Patients with Neuropsychiatric Systemic Lupus Erythematosus

Background：Conventional magnetic resonance imaging （MRI） is the preferred neuroimaging method in the evaluation ofneuropsychiatric systemic lupus erythematosus （NPSLE）.The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE,to screen for the value of conventional MRI in NPSLE.Methods：A total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study.All patients were classified into different groups according to MRI abnormalities.Both clinical and immunological features were compared between MRI abnormal and normal groups.One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index （SLEDAI） score for MRI abnormalities.Multivariate logistic regression analysis investigated the correlation between immunological features,neuropsychiatric manifestations,and MRI abnormalities.Results：Thirty-six NPSLE patients （61%） showed a variety of MRI abnormalities.There were statistically significant differences in SLEDAI scores （P 〈 0.001）,incidence of neurologic disorders （P =0.001）,levels of 24-h proteinuria （P =0.001） and immunoglobulin M （P =0.004）,and incidence of acute confusional state （P =0.002）,cerebrovascular disease （P =0.004）,and seizure disorder （P =0.028） between MRI abnormal and normal groups.In the MRI abnormal group,SLEDAI scores for cerebral atrophy （CA）,cortex involvement,and restricted diffusion （RD） were much higher than in the MRI normal group （P 〈 0.001,P =0.002,P =0.038,respectively）.Statistically significant positive correlations between seizure disorder and cortex involvement （odds ratio [OR] =14.90;95% confidence interval [CI],1.50-151.70;P =0.023） and cerebrovascular disease and infratentorial involvement （OR =10.00;95% CI,1.70-60.00;P =0.012） were found.Conclusions：MRI abnormalities in NPSLE,especially CA,cortex involvement,and RD might be markers of high systemic lupus erythematosus activity.Some MRI abnormalities might correspond to neuropsychiatric manifestations and might be helpful in understanding the pathophysiology of NPSLE.

系统性红斑狼疮低疾病活动度及缓解状况的真实世界研究

目的:研究系统性红斑狼疮(systemic lupus erythematosus, SLE)患者的真实世界低疾病活动度和临床缓解率,并分析其相关因素。方法:采用现场调查的研究方法,对国内11家医院1 000例SLE患者进行问卷调查,记录患者的一般资料、临床表现、实验室检查结果和治疗情况等。采用狼疮低疾病活动状态(lupus low disease activity state, LLDAS)和SLE缓解定义(definitions of remission in SLE,DORIS)评价患者低疾病活动度和临床缓解率,进一步分析符合LLDAS或DORIS缓解患者的临床特征。多因素Logistic回归分析影响LLDAS或DORIS缓解的相关因素。结果:1 000例SLE患者中,207例(20.7%)符合LLDAS标准,104例(10.4%)符合DORIS缓解。与不符合LLDAS或DORIS的患者相比,符合LLDAS或DORIS者高收入比例更高,病程更长,贫血、肌酐升高、红细胞沉降率增快和低白蛋白血症的发生率更低。应用羟氯喹>12个月或免疫抑制剂≥6个月的SLE患者缓解比例较高。多因素Logistic回归分析发现,红细胞沉降率增快、抗双链DNA抗体阳性、低补体血症(C3和C4)、蛋白尿及家庭收入低是不利于达到LLDAS或DORIS缓解的独立相关因素,而应用羟氯喹>12个月为达到LLDAS或DORIS缓解的保护因素。结论:SLE患者达到LLDAS或DORIS缓解状态的比例较低,规范应用羟氯喹和免疫抑制剂有助于患者的病情缓解。

新型细胞因子Metrnl与系统性红斑狼疮中巨噬细胞极化及其疾病活动度的关联研究

目的探讨镍纹样蛋白(Metrnl)在系统性红斑狼疮(SLE)及其严重并发症狼疮性肾炎(LN)患者中的水平,并探讨其与巨噬细胞极化状态及疾病活动度的关联。方法选取2023年6月至2024年5月该院收治的80例SLE患者作为研究对象,分为LN组(40例)和无LN组(40例),另选取同期该院30例年龄、性别匹配的健康体检者作为对照组。采用酶联免疫吸附试验检测Metrnl、M1型标志蛋白(iNOS)、M2型标志蛋白(Arg-1)、肿瘤坏死因子(TNF)-α和白细胞介素(IL)-10水平。采用Pearson相关分析SLE患者Metrnl水平与各项常规实验室指标水平,以及iNOS、Arg-1、TNF-α、IL-10的相关性。采用受试者工作特征(ROC)曲线分析Metrnl在SLE和LN中的诊断价值。结果LN组平均Metrnl水平为(98.35±37.12)pg/mL,明显低于无LN组的(167.89±25.74)pg/mL和对照组的(257.89±22.45)pg/mL,差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,SLE患者Metrnl水平与TNF-α水平均呈负相关(r=-0.328,P=0.015),与Arg-1、IL-10水平均呈正相关(r=0.538、0.489,P<0.05)。ROC曲线分析结果显示,Metrnl诊断SLE患者和健康体检者的曲线下面积(AUC)为0.88,灵敏度为90.32%,特异度为76.00%;诊断无LN患者和LN患者的AUC为0.83,灵敏度为87.10%,特异度为73.53%。结论Metrnl在SLE及LN的免疫调控中发挥重要作用,可能通过影响巨噬细胞极化状态调节疾病活动度。SLE患者血清Metrnl水平与炎症因子等临床指标水平均有明显相关性,为其作为评估疾病活动度和治疗反应的潜在生物标志物提供了理论依据。

系统性红斑狼疮患者凝血-纤溶功能变化与疾病活动的关系

目的观察系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)患者凝血—纤溶功能变化,探讨其与SLE疾病活动指标及不同系统损害的关系。方法选择我院SLE患者109例及100例健康体检者,抽取外周静脉血,检测凝血—纤溶指标[活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)、纤维蛋白(原)降解产物(FDP)、D-2聚体(DD)]与SLE疾病活动指标[血沉(ESR)、补体(C)3、C4、抗双链DNA抗体(抗dsDNA抗体)、C反应蛋白(CRP)、免疫球蛋白G(IgG)、IgM、IgA],比较不同疾病活动度及不同系统损害的SLE患者血浆APTT、PT、TT、FIB、FDP、DD指标差异,采用pearson或Spearman秩相关分析法分析APTT、PT、TT、FIB、FDP、DD水平与SLE疾病活动指标的相关性;采用单因素及多因素Logistic回归分析法分析SLE患者疾病活动的影响因素。结果与健康体检者相比,SLE患者血浆PT、FIB、FDP、DD水平升高(P均<0.05);与非活动期[系统性红斑狼疮疾病活动度(SLEDAI)评分<5分]者比较,疾病活动期(SLEDAI评分≥5分)的SLE患者血浆FIB、FDP、DD水平高(P均<0.05)。与无肾脏病变者比较,出现肾脏病变的SLE患者血浆FIB、FDP、DD水平高(P均<0.05);与无间质性肺炎(ILD)者相比,存在ILD的SLE患者血浆FIB水平高(P<0.05);与未出现浆膜炎患者相比,出现浆膜炎的SLE患者血浆PT、APTT、FDP、DD水平高;与无血液系统受累者相比,存在血液系统受累的SLE患者血浆PT、APTT长(P均<0.05)。SLE患者血浆PT水平与ESR呈正相关、与C3呈负相关(P均<0.05);APTT与ESR、IgG、抗dsDNA抗体水平呈正相关,与C3、C4呈负相关(P均<0.05);FIB与ESR、IgG、C4、IgA水平及SLEDAI评分均呈正相关(P均<0.05)。SLE患者血浆DD与ESR、CRP、IgG、抗dsDNA抗体水平及SLEDAI评分呈正相关(P均<0.05);FDP与ESR、CRP、IgG、抗dsDNA抗体水平及SLEDAI评分呈正相关(P均<0.05)。单因素Logistic回归分析结果显示,FIB、ESR、IgA、IgG、抗dsDNA抗体升高及C3降低是SLE疾病活动危险因素(P均<0.05);多因素Logistic回归分析结果显示,FIB、ESR、IgG、抗dsDNA抗体水平升高是影响SLE疾病活动的独立危险因素(P均<0.05)。结论SLE患者血浆PT、FIB、DD、FDP水平升高,且疾病活动组及不同系统损害SLE患者存在不同凝血—纤溶指标的升高。血浆FIB、ESR、IgG、抗dsDNA抗体水平升高提示SLE疾病活动,凝血—纤溶指标异常可能提示SLE不同系统损害发生。

血清ICAM-1、IL-6水平与系统性红斑狼疮患者疾病活动度的关系及评估颈动脉粥样硬化的价值

目的 研究血清细胞间黏附分子(ICAM-1)、白细胞介素-6(IL-6)与系统性红斑狼疮(SLE)患者疾病活动性的相关性,并探讨其评估颈动脉粥样硬化(CA)的临床价值。方法 回顾性选取2021年1月至2023年12月广西医科大学附属柳州市人民医院收治的SLE患者98例作为研究对象,设为SLE组。按SLE疾病活动指数(SLEDAI)-2000将其分为中重度活动(SLEDAI≥10分)组(n=53)与轻度活动(SLEDAI<10分)组(n=45);并按是否合并CA将患者分为CA组(n=29)与非CA组(n=69)。另选取同期健康体检者50名作为对照组。比较各组血清ICAM-1、IL-6水平,比较CA组与非CA组的临床资料[性别、年龄、体重指数、吸烟史、饮酒史、高血压、高脂血症、SLEDAI评分、C反应蛋白(CRP)、红细胞沉降率(ESR)、补体(C3、C4)],并使用多因素Logistic回归分析影响SLE并发CA的相关因素;用受试者操作特征(ROC)曲线评价血清ICAM-1、IL-6对SLE并发CA的评估能力。结果 SLE组血清ICAM-1、IL-6水平分别为(150.47±46.39)ng/mL、(21.54±5.49) pg/mL,均显著高于对照组[(65.52±19.46)ng/mL、(9.31±2.35) pg/mL],差异均有统计学意义(P<0.05)。中重度活动患者血清ICAM-1、IL-6水平分别为(177.41±42.36) ng/mL、(25.31±4.78) pg/mL,均显著高于轻度活动患者[(118.74±38.21) ng/mL、(17.10±4.23) pg/mL],差异均有统计学意义(P<0.05)。CA组合并高血压比例、SLEDAI评分、血清CRP、ICAM-1和IL-6水平分别为48.28%、(13.96±2.04)分、(4.36±1.42) mg/L、(171.58±38.41) ng/mL、(24.31±4.27) pg/mL,均高于非CA组[17.39%、(7.41±2.13)分、(3.72±1.19) mg/L、(141.60±42.34) ng/mL、(20.38±5.11) pg/mL],而补体C3、C4水平分别为(0.38±0.11)、(0.09±0.02)g/L,均低于非CA组[(0.57±0.16)、(0.14±0.04)g/L],差异均有统计学意义(P<0.05)。经Logistic回归分析得出,高血压、血清较高ICAM-1水平、较高IL-6水平均是患者并发CA的危险因素(OR=1.110,95%CI:1.016~1.212;OR=1.239,95%CI:1.078~1.424;OR=1.217,95%CI:1.079~1.371;P<0.05)。ROC曲线分析得出,血清ICAM-1、IL-6评估SLE并发CA的曲线下面积(AUC)分别为0.735、0.722,二者联合的AUC为0.810,相比单项指标显著增大(P<0.05)。结论 SLE患者血清ICAM-1、IL-6水平增高与疾病活动度相关,且对SLE并发CA有评估价值。

血清anti-β2GPI、FSTL1、PD-1对系统性红斑狼疮免疫功能、疾病活动度的影响

目的探究血清抗β2糖蛋白I抗体(anti-β2GPI)、卵泡抑素样蛋白(FSTL1)、程序性死亡受体1(PD-1)对系统性红斑狼疮(SLE)患者免疫功能、疾病活动度的影响。方法选取我院2019年1月~2022年6月SLE患者113例作为观察组,另选取同期健康体检者105例作为对照组。比较两组、不同疾病活动度患者血清anti-β2GPI、FSTL1、PD-1水平,评价各血清指标与疾病活动度的关系,并根据观察组血清表达水平分为高表达者、低表达者,对比两者免疫功能(CD4+、CD8+、CD4+/CD8+),分析各血清指标与免疫功能相关性。结果观察组血清anti-β2GPI、FSTL1、PD-1高于对照组(P<0.05);血清anti-β2GPI、FSTL1、PD-1高表达患者CD4+、CD4+/CD8+低于低表达患者,CD8+高于低表达患者(P<0.05);血清anti-β2GPI、FSTL1、PD-1与CD4+、CD4+/CD8+呈负相关,与CD8+呈正相关(P<0.05);血清anti-β2GPI、FSTL1、PD-1水平随疾病活动度增加呈升高趋势,且重度活动患者>中度活动患者>轻度活动患者>病情稳定患者(P<0.05);血清anti-β2GPI、FSTL1、PD-1与疾病活动度显著相关(P<0.05)。结论血清anti-β2GPI、FSTL1、PD-1高表达可能参与SLE患者细胞免疫功能紊乱、疾病活动度加重的发生过程。

系统性红斑狼疮患者外周血中γδT细胞及其主要功能亚群的变化及临床意义

目的探讨系统性红斑狼疮(SLE)患者外周血中γδT细胞及其主要功能亚群γδT1、γδT17细胞的变化及其临床意义。方法采用流式细胞术检测21例SLE患者(SLE组)、16例健康对照患者(HC组)外周血γδT细胞、γδT1细胞、γδT17细胞的比例及绝对数。采用Pearson相关性分析法分析外周血γδT细胞、γδT1细胞、γδT17细胞与临床指标的相关性。结果SLE患者外周血γδT细胞占淋巴细胞百分率为(2.30±1.10)%,低于HC组的(3.30±1.51)%,差异有统计学意义(P<0.05);γδT1细胞占淋巴细胞百分率为(0.93±0.67)%,低于HC组的(2.09±1.21)%,差异有统计学意义(P<0.001);γδT17细胞占淋巴细胞比率为(1.53±2.82)‰,与HC组的(0.18±0.12)‰比较有增多的趋势,但差异无统计学意义(P>0.05)。SLE患者外周血γδT细胞绝对数为(2.88±2.18)×10^(4)/mL,低于HC组的(7.96±3.96)×10^(4)/mL,差异有统计学意义(P<0.0001);SLE患者外周血γδT1细胞绝对数为(1.20±1.17)×10^(4)/mL,低于HC组的(5.05±3.04)×10^(4)/mL,差异有统计学意义(P<0.0001);SLE患者外周血γδT17细胞绝对数为(1.03±1.08)×103/mL,高于HC组的(0.40±0.24)×103/mL,差异有统计学意义(P<0.05)。SLE患者外周血中γδT17细胞比例与系统性红斑狼疮疾病活动度评分(SLEDAI)(r=0.59,P<0.01)、红细胞沉降率(r=0.65,P<0.01)呈正相关,γδT17细胞绝对数与SLEDAI(r=0.59,P<0.01)呈正相关,与补体C3水平(r=-0.53,P<0.05)呈负相关。结论SLE患者外周血中γδT细胞数量显著下降主要由其γδT1细胞亚群减少所致,γδT17细胞在SLE发病及活动中发挥了重要作用。

全身免疫炎症指数与溃疡性结肠炎疾病活动度的相关性研究

目的分析溃疡性结肠炎(UC)患者的全身免疫炎症指数(SII)水平,并评估其与疾病活动度的关系。方法纳入UC患者161例(UC组)和同期健康体检者150例(对照组)。采用改良Mayo评分评估UC组患者的疾病活动度,将其分为缓解期组26例和活动期组135例[其中轻度活动组(30例)、中度活动组(67例)和重度活动组(38例)]。收集所有受试者的一般临床特征和实验室检查指标,比较各组患者外周血SII、血小板与淋巴细胞比值(PLR)、中性粒细胞与淋巴细胞比值(NLR)等炎症指标的差异。采用Spearman相关分析评估SII与UC疾病活动度的相关性,采用受试者工作特征(ROC)曲线评估SII对UC活动期严重程度的预测价值。结果UC组患者PLR、PLT计数、NLR、中性粒细胞计数(Neu)及SII均显著高于对照组,Hb、年龄均显著低于对照组(P<0.001)。活动期组患者Neu、PLT计数、NLR、PLR、SII、C反应蛋白(CRP)及红细胞沉降率(ESR)均显著高于缓解期组,LYM显著低于缓解期组(P<0.05)。轻度活动组、中度活动组和重度活动组患者Neu、PLT计数、NLR、PLR、SII、CRP、ESR均依次升高;轻度活动组和中度活动组患者Hb水平均高于重度活动组(P<0.05)。Spearman相关分析结果显示,Neu、PLT计数、NLR、PLR、SII、CRP、ESR与UC疾病活动度及UC活动期严重程度均呈正相关,Hb与UC活动期严重程度呈负相关(P<0.001)。ROC曲线分析结果显示,ESR、PLR、PLT计数、NLR、Neu、CRP及SII对活动期UC和重度UC均具有一定预测价值(P<0.001),其中SII的AUC均最大。结论SII可能有助于评估UC疾病活动度和活动期严重程度。

全身免疫炎症指数与系统性红斑狼疮患者疾病活动度的关联分析

目的通过评估全身免疫炎症指数(systemic immune inflammatory index,SII)水平与系统性红斑狼疮(systemic lupus erythematosus,SLE)患者的疾病活动度之间的关系,探索SLE患者疾病活动度简便评估的新方法;方法收集在昆明医科大学第一附属医院风湿免疫科就诊的SLE患者临床资料,根据系统性红斑狼疮活动指数(SLEDAI)分组,比较、分析SII水平与疾病活动的相关性,绘制接受者工作特征曲线(receiver operating characteristic curve,ROC),评价SII对SLE疾病活动度的预测价值。结果SLE患者疾病轻度活动组的SII水平显著低于重度活动组(经Bonferroni校正,P<0.05/3=0.017),SII水平与SLEDAI评分存在相关性(r=0.130,P<0.05),ROC曲线下面积为0.581(P<0.05)。结论SII可作为反映SLE疾病活动度的一种简便、快速的参考指标。

系统性红斑狼疮疾病活动度相关特征分析及评估模型的构建

目的:对系统性红斑狼疮(systemic lupus erythematosus,SLE)患者进行临床分层,分析不同活动度患者的临床特征,并探讨关键临床指标在SLE疾病活动度评估中的应用价值及评估模型的构建。方法:回顾性分析1995年5月至2014年4月北京大学人民医院确诊的SLE患者临床资料。收集患者的人口学信息、临床表现、实验室检查结果,根据SLE疾病活动度指数2000(systemic lupus erythematosus disease activity index 2000,SLEDAI-2000)将患者分为疾病活动组与无疾病活动组。采用t检验、Mann-Whitney U检验以及χ^(2)检验比较两组间差异,并使用Spearman相关性分析评估疾病活动组中与SLE活动度相关的临床指标。基于统计学分析结果,构建了逻辑回归模型,并对模型性能进行评估。结果:两组在基本人口学特征上差异无统计学意义。疾病活动组中,抗核抗体(antinuclear antibodies,ANA)及抗双链DNA抗体(anti-double-stranded DNA antibodies,anti-dsDNA)阳性率升高;白细胞计数(white blood cell,WBC)、红细胞计数(red blood cell,RBC)、血红蛋白(hemoglobin,HGB)、淋巴细胞(lymphocytes,LY)、总蛋白(total protein,TP)、白蛋白(albumin,ALB)及补体C3水平显著降低,免疫球蛋白A(immunoglobulin A,IgA)、免疫球蛋白G(immunoglobulin G,IgG)水平明显升高。相关性分析结果显示,血红蛋白、白蛋白、补体C3和补体C4与其他临床指标相比具有更高的相关性指数,其中补体C3与疾病活动度具有一定负相关性。基于12项差异具有统计学意义的指标构建的逻辑回归模型准确率为91.4%,敏感性为94.4%,特异性为81.0%,受试者工作特征曲线(receiver operating characteristic,ROC)的线下面积(area under curve,AUC)为0.944。结论:全面评估与SLE疾病活动度相关的临床指标,以实验室检查指标为主构建的逻辑回归模型能够较准确地评估SLE患者疾病活动度,为SLE患者的个体化治疗提供参考。

贝利尤单抗治疗中国成人狼疮性肾炎有效性和安全性的Meta分析

目的系统评价真实世界中贝利尤单抗治疗中国成人狼疮性肾炎(LN)患者的有效性和安全性。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、万方、中国知网、维普、中国生物医学文献数据库,搜集贝利尤单抗治疗中国成人LN患者的真实世界研究,检索时限均从建库至2023年7月7日。由2位评价员独立筛选文献、提取资料并评价纳入研究的质量后,采用RevMan 5.3软件进行Meta分析。结果共纳入10篇真实世界研究,包括253例中国成人LN患者。Meta分析结果显示,贝利尤单抗治疗中国成人LN患者的肾脏完全缓解率、肾脏部分缓解率、不良反应发生率分别为61%(95%CI为46%~76%,P<0.00001)、23%(95%CI为2%~44%,P=0.03)、30%(95%CI为16%~43%,P<0.00001);贝利尤单抗可显著降低24 h尿蛋白水平(MD=-1.71,95%CI为-3.02~-0.40,P=0.01)、尿总蛋白肌酐比值(MD=-1.76,95%CI为-2.06~-1.46,P<0.00001)、系统性红斑狼疮疾病活动度指数(MD=-8.63,95%CI为-12.12~-5.13,P<0.00001)和糖皮质激素用量(MD=-18.65,95%CI为-31.82~-5.48,P=0.006),显著升高补体C3水平(MD=0.19,95%CI为0.08~0.30,P=0.0006)和补体C4水平(MD=0.06,95%CI为0.02~0.09,P=0.001),但不能改善血清肌酐水平和估算肾小球滤过率(P>0.05)。结论贝利尤单抗对中国成人LN患者具有良好的有效性和安全性。

SLE患者经泼尼松治疗后NLR、PLR及NC3R水平变化与其疾病活动度的关系

目的探讨系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)患者中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值、中性粒细胞与补体C3的比值与疾病活动度的关系,并根据其水平变化评估患者疾病活动度。方法前瞻性方便选取2022年9月—2023年9月高邮市中医医院收治的86例SLE患者为研究对象,根据患者治疗前SLE疾病活动度评分分为轻度活动组、中度活动组、重度活动组,患者均口服泼尼松连续治疗3个月,比较治疗前后疾病活动度及实验室指标。结果重度活动组中性粒细胞与淋巴细胞比值(Neutrophil to Lymphocyte Ratio,NLR)、血小板与淋巴细胞比值(Platelet to Lymphocyte Ratio,PLR)水平高于轻度活动组和中度活动组,中性粒细胞与补体C3的比值(Neutrophil to Complement C3 Ratio,NC3R)水平低于轻度活动组和中度活动组,差异有统计学意义(P均<0.05);NLR、PLR与疾病活动度正相关(r=0.053、0.299,P均<0.05),NC3R与疾病活动度负相关(r=-0.673,P<0.05)。结论SLE患者经泼尼松治疗后NLR、PLR及NC3R水平变化与疾病活动度密切相关。

初诊SLE患者抗CTLA-4抗体水平及其临床意义

目的探讨初诊系统性红斑狼疮(SLE)患者血清中抗CTLA-4抗体水平及其临床意义。方法选取2022年1月至2023年6月在苏州大学附属第一医院风湿免疫科就诊的初诊SLE患者56例作为病例组,同时选取我院体检中心52例体检者作为对照组。采用酶联免疫吸附试验(ELISA)检测两组血清中IgG和IgM型抗CTLA-4抗体。比较不同临床特征(包括皮疹、口腔溃疡、浆膜炎等等)初诊SLE患者组间抗CTLA-4抗体水平差异。采用Pearson相关分析评估初诊SLE患者抗CTLA-4抗体与疾病活动指标[包括SLE疾病活动指数2000版(SLEDAI-2K)、抗ds-DNA以及C反应蛋白(CRP)]的关系。结果病例组IgG和IgM型抗CTLA-4水平均高于对照组(t=4.657、5.014,P均<0.05);IgG和IgM型抗CTLA-4抗体水平在SLE合并浆膜炎的患者中高于未合并浆膜炎患者(t=1.849、2.013;P=0.046、0.032);Pearson相关分析显示,IgM型抗CTLA-4抗体与SLEDAI-2K(r=0.425,P=0.029)及补体C3(r=-0.494,P=0.029)呈正相关;IgG和IgM型抗CTLA-4抗体与CRP(r=0.301、0.404;P=0.041、0.022)和抗ds-DNA抗体(r=0.644、0.363;P=0.002、0.036)呈正相关。结论初诊SLE患者血清抗CTLA-4抗体呈高表达,且该抗体与浆膜炎、疾病活动度相关。

系统性红斑狼疮患者外周血T淋巴细胞Mg^(2+)转运蛋白1水平表达及临床价值研究

目的探讨Mg^(2+)转运蛋白1(magnesium transporter protein 1,MagT1)在系统性红斑狼疮(systemic lupuserythematosus,SLE)患者外周血T淋巴细胞中的表达情况,并阐述其临床意义。方法选取西双版纳傣族自治州人民医院2019年1月~2021年6月收治的79例SLE患者作为研究对象,依据SLE疾病活动指数(SLE disease activityindex,SLEDAI)评分将SLE患者分为中重度组(SLEDAI≥10,n=32)和轻度组(SLEDAI<10,n=47),另选取同期体检健康者40例作为对照组。记录患者临床生化和血清免疫相关指标水平;采用实时定量PCR(quantitative realtimePCR,qRT-PCR)法和Western Blot法检测患者外周血T淋巴细胞中MagT1 mRNA和蛋白表达情况;Pearson相关性分析外周血T淋巴细胞MagT1蛋白与生化免疫相关指标表达的关系;绘制受试者工作特征(receiver operatingcharacteristic,ROC)曲线分析外周血T淋巴细胞MagT1蛋白表达对SLE及其严重程度的诊断价值。结果与对照组比较,轻度组和中重度组患者外周血T淋巴细胞中MagT1 mRNA[0.65(0.36,0.99),0.23(0.07,0.36)vs 1.20(0.83,1.37)]和MagT1蛋白[0.35(0.22,0.42),0.22(0.15,0.27)vs 0.53(0.40,0.63)]表达水平明显降低,差异具有统计学意义(Z=5.247,7.078;5.128,7.257,均P<0.05);与轻度组比较,中重度组患者外周血T淋巴细胞中MagT1 mRNA和蛋白表达水平明显降低,差异具有统计学意义(Z=5.169,3.599,均P<0.05)。Pearson相关性结果显示,外周血T淋巴细胞MagT1蛋白表达水平与血清血红蛋白(hemoglobin,HGB)及补体3(complement 3,C3)和补体4(complement 4,C4)水平呈正相关(r=0.496,0.637,0.588,均P<0.05);与红细胞沉降速率(erythrocyte sedimentation rate,ESR)、超敏C反应蛋白(hypersensitive-C reactive protein,hs-CRP)、免疫球蛋白(immunoglobulin G,IgG)水平和SLEDAI呈负相关(r=-0.598,-0.476,-0.646,-0.514,均P<0.05)。ROC曲线结果显示,外周血T淋巴细胞MagT1蛋白表达水平诊断SLE曲线下面积为0.893(95%CI:0.838~0.948),敏感度和特异度分别为90.0%,67.1%,诊断SLE严重程度曲线下面积为0.739(95%CI:0.631~0.848),敏感度和特异度分别为57.4%,84.4%。结论外周血T淋巴细胞MagT1在SLE患者中表达下调,且与SLE严重程度呈负相关,对SLE诊断和病情严重程度具有一定的诊断价值。