神经精神性狼疮患者的临床特点

目的了解神经精神性狼疮(neuropsychiatric systemic lupus erythematosus,NPSLE)患者的临床特点,加强对该病的认识,以指导临床进行早期诊断和治疗,改善疾病预后。方法选取2011年6月—2016年6月在海南省人民医院住院的82例NPSLE患者作为病例组,同期收集本院确诊为系统性红斑狼疮(systemic lupus erythematosus,SLE)但无神经精神症状的82名住院患者作为对照组,了解NPSLE患者神经精神症状,并比较两组患者的一般情况、临床表现、实验室和免疫学检查。结果 82例NPSLE患者,男性9例,女性73例,年龄(33.2±16.7)岁,病程1年者占69.5%,病例组患者病程要短于对照组(P0.05);62.2%的NPSLE患者在SLE发病3年内出现神经精神症状,常见的症状为狼疮性头痛(20.0%)、癫痫(12.0%)、性格改变(10.5%)和焦虑(10.5%),85.4%的患者合并有其他临床表现,主要为面部红斑(68.3%)、肾脏受累(59.8%)、关节疼痛(42.7%)等,与对照组相比,NPSLE患者更易合并光感性皮疹(P0.05);两组患者血小板、血肌酐、补体C4、免疫球蛋白Ig M、抗ds-DNA抗体、抗r-RNP抗体差异有统计学意义(P0.05)。结论 NPSLE患者偏向于青年女性,常发生于SLE病程的早期阶段,大部分患者在SLE发病3年内会出现神经精神症状,且更易合并光感性皮疹,血小板、肌酐、补体C4的降低和Ig M、抗ds-DNA抗体、抗r-RNP抗体水平的升高可辅助NPSLE进行早期诊断和预测。     

Gender differences are associated with the clinical features of systemic lupus erythematosus

Background  Systemic lupus erythematosus (SLE) mostly occurred in young women. This study was undertaken to investigate the different clinical characteristics of SLE between male and female patients, and to identify the sex hormone levels and clinical outcomes of different gender in SLE patients.

Methods  Of the 516 SLE patients admitted to the Peking University People’s Hospital from January 2008 to December 2010, 58 were male and 458 were female. Clinical manifestations, laboratory profiles and disease activity scores were evaluated in male and female patients. Sex hormones levels were also compared among male patients.

Results  The median age at SLE onset in male and female patients was 27.2 and 28.6 years, respectively. Compared with female patients, at onset of SLE, male patients showed higher rates of serious renal disease (58.6% vs. 47.2%, P=0.064), neuropsychiatric SLE (20.7% vs. 12.0%, P=0.055), and a higher incidence of anti-ds-DNA (25.9% vs. 16.8%, P=0.069), anti-Sm (17.2% vs. 8.7%, P=0.002), anti-Ro (46.6% vs. 28.4%, P=0.004), anti-U1RNP (29.3% vs. 15.3%, P=0.010), anticardiolipin antibody (25.9% vs. 11.4%, P=0.004), and decreased C3 levels (67.2% vs. 49.8%, P=0.009). Systemic lupus erythematosus disease activity index (SLEDAI) scores were higher in men than in women (16.8 vs. 12.8, P=0.038). Of the 58 male patients, 24 had not received aggressive treatment during the three months prior to the study. Levels of testosterone and dihydroepiandrosterone (DHEA) were lower in male SLE patients than in male healthy controls (P=0.004 and P=0.006, respectively). Low serum testosterone was an independent risk factor for the development of lupus nephritis (P=0.043). Male patients with elevated serum prolactin were at increased risk of developing neuropsychiatric manifestations of SLE (P=0.081).

Conclusion  Early recognition of risk factors and appropriate intervention are essential, which might lead to high disease activity and serious systemic damage in male SLE patients.

     

中国人CTLA-4基因-1722位点多态性与系统性红斑狼疮的相关性

目的 研究细胞毒性T淋巴细胞相关抗原4(cytotoxic Tlymphocyte-associated antigen 4,CTLA-4)基因启动子区-1722位点(T/C)多态性在中国南方地区汉族人群中的分布及其与系统性红斑狼疮(SLE)的相关性。方法 103例患者诊断均符合1982年美国风湿病学会修订的SLE分类标准,其中男13例,女90例。正常对照组110例,其中男21例,女89例。全部研究对象均为无血缘关系的中国南方汉族人群。采用微量全血提取法,从EDTA抗凝血中提取DNA。应用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法,对所有SLE患者和正常对照者进行CTLA-4基因-1722位点多态性检测。结果 CTLA-4基因-1722位点多态性在中国南方地区人群中普遍存在,与正常对照组比较,SLE患者CTLA-4基因-1722位点TC基因型频率明显升高(42%vs58%,P<0.05),CC基因型频率明显降低(25%vs15%,P<0.05),TT基因型频率虽有降低趋势,但差异无显著性(33%vs27%,P>0.05);而SLE患者等位基因频率和携带者频率分布均无显著性差异(P>0.05)。在不同人种CTLA-4基因-1722位点基因型频率和等位基因频率分布存在差异。结论 CTLA-4基因-1722位点多态性与SLE明显相关,CTLA-4基因可能是SLE的易感基因。     

细胞毒性T淋巴细胞相关抗原-4基因启动子区多态性与系统性红斑狼疮的遗传易感性

目的 探讨细胞毒性T淋巴细胞相关抗原-4（cytotoxic T lymphocyte-associated antigen 4,CTLA-4）基因启动子区多态性与系统性红斑狼疮（systemic lupus erythematosus,SLE）发病的相关性.方法 以医院为基础的病例对照研究,应用PCR-RFLP技术分析了97例SLE患者和200例对照在启动子区-1722 T＞C和-318 C＞T位点的多态性.结果 SLE患者组-1722 T＞C位点TT基因型频率高于对照组（P=0.002）,患者中的T等位基因比例高于对照组（OR=1.94,95%CI：1.34-2.80,P=0.000）;而在-318 C＞T位点,病例组和对照组的基因型频率和等位基因频率分布无显著差异.但是,两位点等位基因间存在连锁不平衡（精确P＜0.05）,且在病例组和对照组,单倍型频率分布不同（x^2=12.64,P=0.005）;其中,与对照组相比,病例组中T-C单倍型具有较高的频率（P=0.001）而C-C单倍型频率较低（P=0.002）.结论 CTLA-4基因-1722 T＞C位点多态与SLE易感性有关.虽然本次研究结果未发现-318 C＞T位点多态与SLE发病相关,但发现T-C单倍型为SLE易感单倍型,而C-C单倍型为其保护单倍型.     

汉族人系统性红斑狼疮和狼疮肾炎与IL-22受体基因多态性的关系

摘要：目的  对汉族人群系统性红斑狼疮患者白细胞介素22（IL-22）受体基因多态性进行研究,探讨其与系统性红斑狼疮和狼疮肾炎的关系。方法  选取2012年1月-2016年6月吉林大学第一医院系统性红斑狼疮患者360例和健康者360例作为研究对象,将其分为A组（系统性红斑狼疮组）和B组（对照组）;系统性红斑狼疮患者分为C组（狼疮肾炎组）和D组（无狼疮肾炎组）。观察IL-22R1基因rs3795299位点基因型和等位基因频率与系统性红斑狼疮、狼疮肾炎及系统性红斑狼疮临床特点的关系。结果  A组与B组IL-22R1基因rs3795299位点基因型和等位基因频率比较,差异无统计学意义（P >0.05）。C组患者GG基因型所占比例高于D组患者（P <0.05）,CG和CC基因型所占比例低于D组患者（P <0.05）;C组患者等位基因G频率低于D组（P <0.05）,等位基因C频率高于D组（P <0.05）。IL-22R1基因rs3795299位点等位基因频率在系统性红斑狼疮患者有关节炎、面部红斑、光敏感和口腔溃疡患者中的分布与无关节炎、面部红斑、光敏感和口腔溃疡患者中的分布不同,差异有统计学意义（P <0.05）。结论  在中国汉族人群中,IL-22R1基因rs3795299位点基因多态性与系统性红斑狼疮的易感性无关,与狼疮肾炎的易感性有关,与系统性红斑狼疮的临床特点相关。

     

汉族人群系统性红斑狼疮的易感位点及其多态性的相关性研究

目的 研究系统性红斑狼疮(SLE)的易感位点、基因及其多态性与汉族人群SLE易感性的关系.方法 应用Sequenom MassArray质谱阵列技术对5×10-6相似文献   

Toll-like receptor 9 is correlated to disease activity in Chinese systemic lupus erythematosus population

Background  Toll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE.

Methods  mRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR). IFN-a expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA).

Results  TLR9 expression was significantly higher in SLE patients than that in health controls (P=0.011). SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P=0.001). TLR9 expression was positively correlated with fever (P=0.017), alopecia (P=0.046), safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (r_s=0.385, P=0.003), and the level of IRF5 (r_s=0.35, P=0.027) and IFN-a (r_s=0.627, P=0.001) in SLE patients.

Conclusion  TLR9 is associated with SLE disease activity and might be involved in the IFN-a pathway of SLE.

     

皖籍汉人系统性红斑狼疮的遗传流行病学研究

目的探讨系统性红斑狼疮（SLE）可能的遗传模式,并分析皖籍汉人SLE的遗传流行病学特征。方法采用调查表的形式收集患者的临床及家系资料,用Epi Info6．0及SPSS13．0软件包进行统计学分析,用SAGE3．1进行遗传模式的复合分离分析。结果平均发病年龄为30．2岁,平均病程为32．5个月。SLE存在多主基因效应、主基因模型拟合最好,支持在多基因基础上符合孟德尔遗传的主基因效应。结论遗传因素在SLE的发病中起着重要作用,SLE遵循多主基因遗传模式而非单基因遗传模式。     

系统性红斑狼疮17例分析

系统性红斑狼疮(SLE)多发于青中年女性,临床表现多样化。本文按美国风湿病学会(ARA)1982年修订的SLE诊断标准,选择17例住院SLE进行了分析,指出应注意对早期、不典型的病例的诊断,治疗方案和药物剂量必须根据病情活动情况而定,救冶狼疮性肾炎(LN)及减少激素用量是治疗中的重要问题。     

系统性红斑狼疮患者C4零基因对C4含量的影响

目的分析系统性红斑狼疮中C4零基因对SLE患者血清中补体C4含量的影响.方法采用国际参考实验室的方法及计算机凝胶图像光密度分析系统检测45例广东籍汉族人SLE患者,同时用单向免疫扩散法检测这些患者血清中补体C4含量.结果含 C4零基因的SLE患者血清中C4含量低于不含 C4零基因患者的C4含量(P < 0.05).结论 C4零基因的存在可引起SLE患者血清中补体C4含量下降.     

系统性红斑狼疮胸部X线平片的诊断价值

目的:探讨系统性红斑狼疮(SLE)患者的胸部X线表现,以提高对本病的认识.方法:分析56例SLE患者的临床和胸部X线资料.结果:56例SLE患者的胸部X线检查有46例可见异常,主要表现为肺部、心脏、胸膜和膈肌的浸润.结论:X线检查对SLE胸部病变的诊断具有重要价值,但其影像学表现不具有特异性,必须密切结合临床资料综合分析.     

Osteopontin gene polymorphism in association with systemic lupus erythematosus in Chinese patients

Background Osteopontin (OPN) is one kind of cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between Th1 and Th2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Some researches have showed that OPN may be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate possible association of a single nucleotide polymorphism（SNP）at position 9250 in exon 7 of the OPN gene (OPN gene 9250) with SLE in Chinese patients.Methods Totally 158 patients (18 males and 140 females) fulfilled the revised criteria for SLE by the American College of Rheumatology in 1982 and 180 healthy volunteer controls (34 males and 146 females), all from the south of China, consented to participate in the study. OPN gene 9250 polymorphism was detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).Results The frequency of TT genotype of the OPN gene 9250 was significantly lower (52.5% vs 70%, P&lt;0.05) and the frequency of TC genotype of the OPN gene 9250 was significantly higher (43.7% vs 29.4%, P&lt;0.05) in SLE patients than in controls. There were significant differences in OPN gene 9250 allele and phenotype frequencies between the SLE patients and controls (P&lt;0.05). When the SLE patients and controls were separated into men and women, significant differences of frequencies were noted in TT genotype, TC genotype and allele of the OPN gene 9250 in women (P&lt;0.05) but not in men (P&gt;0.05). Conclusions OPN gene 9250 polymorphism appears to be associated with susceptibility to SLE in Chinese Han ethnic population.     

联合检测系统性红斑狼疮患者血尿趋化因子的临床意义

目的了解系统性红斑狼疮(SLE)患者血、尿巨噬细胞炎症蛋白-1α(MIP-1α)、巨噬细胞炎症蛋白-1β(MIP-1β)、激活正常T细胞表达和分泌因子(RANTES)浓度变化并探讨其临床意义。方法用双抗体夹心ELISA方法检测37例SLE患者和20例健康志愿者的血清及尿液的MIP-1α、MIP-1β、RANTES浓度,分析其变化与SLE发病及疾病活动的关系。结果血、尿MIP-1α、MIP-1β浓度在SLE患者显著升高(P<0.001,P=0.003),其中血MIP-1α在狼疮肾炎和非狼疮肾炎患者均显著升高(P<0.01,P=0.004),血MIP-1β主要在非狼疮肾炎患者显著升高(P=0.012);血MIP-1α、MIP-1β浓度在激素治疗后显著降低(P=0.001,P=0.008);血、尿间趋化因子浓度无显著相关,尿RANTES浓度与SLEDAI显著正相关(r=0.515,P=0.014)。结论趋化因子参与了SLE的发病,在不同脏器损害的SLE患者中趋化因子所起的作用不同,血、尿趋化因子浓度间无显著相关,联合检测血、尿趋化因子浓度,有利于评估SLE的脏器损害和疾病活动。     

Pregnancy in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of reproductive age. Pregnancy and its outcome is a major concern to most SLE patients. Queries regarding the risk of disease flares during pregnancy, chance of fetal loss, and the safety of various drugs are often raised. With the improvement in the understanding of the pathogenesis of SLE and the judicious use of immunosuppressive drugs, better disease control can now be achieved and SLE patients should not be deprived of the opportunity for bearing children. Prepregnancy counselling and close collaboration with other specialists such as the obstetricians and the perinatologists is essential in optimising the maternal and fetal outcome in lupus pregnancies. In this review, important issues regarding the fertility rate, optimal timing of conception, risk of disease flares during lupus pregnancy, pregnancy course, fetal outcome, safety of various drugs used for disease control during pregnancy and lactation, and contraceptive advice are discussed.     

系统性红斑狼疮患者Toll样受体9基因多态性的初步研究

目的研究Toll样受体9(TLR9)基因在系统性红斑狼疮(SLE)中是否存在多态性。方法提取26例SLE患者mRNA并逆转录为cDNA,扩增产物经3730 DNA自动测序仪测定TLR9基因序列。结果TLR9 mRNA自起始位点起第1783、2269和3222位碱基存在二态性(A或G),这3个位点为单核苷酸多态性(SNP)位点,分别称之为SNP1、SNP2和SNP3,其中SNP1是我们新发现的多态性位点,SNP2和SNP3为美国国立生物技术信息中心(NCBI)SNP数据库中公布的位点,它们均不改变氨基酸编码。SNP2在人群中可表现为AA纯合、GG纯合或AG杂合3种基因型,在SLE患者中以AG型为主(50%),而在正常人中以GG型为主(75%)(P<0.05);SNP1和SNP3只在一名男性SLE患者中发现,表现为AG杂合,其余个体均为GG纯合。结论TLR9基因编码区中的一个单核苷酸多态性与SLE发病相关联。     

系统性红斑狼疮患者外周血T细胞CTLA-4表达及其临床意义

目的：研究系统性红斑狼疮（systemic lupus erythematosus, SLE）T细胞中CTLA-4的表达及临床意义。方法：分离正常人和SLE患者的外周血单个核细胞（peripheral blood mononuclear cells,PBMCs）,以抗-CD3、抗-CD28刺激培养48 h,刺激培养前后收取细胞,以流式细胞术（FCM）检测CD4+和CD8+T细胞中CTLA-4+细胞比例,并分析其与SLE疾病活动性指数（SLEDAI）和肾损害的关系。再以ELISA法检测培养上清中游离的CTLA-4水平。结果：SLE患者刺激前的CD4+和CD8+T细胞且主要是CD25+T细胞中CTLA-4+细胞的比例较正常人显著增高,与SLEDAI呈正相关;而其CD8+CD28- T细胞中CTLA-4+细胞比例也显著高于正常人,但与SLEDAI之间无显著相关性;经抗-CD3、抗-CD28抗体刺激后,其CD4+CD25+T细胞、CD8+CD25+T细胞或CD8+CD28-T细胞中CTLA-4+细胞的比例却显著低于正常人,但与SLEDAI之间无显著相关性,仅在活动性SLE患者中有肾损组的CD8+CD28-T细胞中CTLA-4+细胞的比例显著低于非肾损组;而且经刺激培养后SLE患者PBMC上清中游离的CTLA-4水平也显著低于正常人。结论：SLE患者新鲜分离的T细胞（CD4+及CD8+）中CTLA-4表达异常增高,反映T细胞异常活化和疾病活动;另一方面,SLE患者T细胞又存在CTLA-4诱导性表达障碍,可能与SLE T细胞体外再活化能力减弱有关。     

不完全系统性红斑狼疮患者的随访研究及病情进展预测

目的 观察不完全系统性红斑狼疮（ILE）患者的临床随访研究结果，探索其病情进展预测因素。方法 对ILE患者定期随访，记录其临床资料及实验室检查结果，随访结束时分析病情进展预测因素。结果 共有19例ILE患者入选本项研究。在3年的随访研究中，有11例ILE患者发展为SLE。危险因素分析显示颡部红斑、光过敏、抗dsDNA抗体阳性与SLE进展相关。结论 在本次随访研究中，虽有58％的ILE患者最后进展为SLE，但所有患者的SLEDAI分值都较低，提示ILE为狼疮的一种比较轻的亚型。颡部红斑、光过敏及抗ds—DNA抗体阳性预示这些患者可能发展为SLE．     

集中环磷酰胺冲击联合泼尼松在初治SLE患者中的疗效

目的:观察集中环磷酰胺(CTX)冲击联合泼尼松在初治系统性红斑狼疮(SLE)患者中的疗效。方法:选取初诊且未经治疗的SLE48例。CTX每2周冲击1次。每次第1dCTX0.4g,第2dCTX0.6g。泼尼松0.8mg/kg体质量。对SLE患者进行SLE活动性指数(SLEDAI)评分。将总分数(SLEDAIT)分成临床评分(SLEDAIc)、实验室评分(SLEDAIL)。分别于治疗前,治疗后4,8,12周进行SLEDAIT、SLEDAIc、SLEDAIL评分。于治疗前及治疗后12周测定尿蛋白、血清补体、血清抗双链DNA抗体(ds-DNA)。结果:共有41例随访至12周。治疗后4周与治疗前比较,SLEDAIT、SLEDAIc及SLEDAIL均明显下降(P<0.01),在8周时SLEDAIc继续下降(P<0.05),而SLEDAIL下降不明显。12周时SLEDAIT变化不明显。12周时与治疗前比较,补体C3、C4及ds-DNA均显著下(P<0.01)降,尿蛋白下降不明显。结论:集中环磷酰胺冲击方案有效。在12周时CTX总量可达6～8g,能迅速缓解病情,而不增加CTX的不良反应,可减少泼尼松的用量。     

89例系统性红斑狼疮患者免疫指标测定的分析

目的：分析免疫学指标对诊断系统性红斑狼疮患者及病情监测的意义。方法：分别应用单向免疫扩散法,间接免疫荧光法、快速斑点免疫印迹技术、形状学方法。结果：活动期ＩｇＧ、ＩｇＡ、ＩｇＭ升高,Ｃ３、Ｃ４下降ＡＮＡ抗体、ｄｓＤＮＡ抗体及ＥＮＡ抗体阳性,淋巴细胞转化率下降;非活动期ＩｇＧ、ＩｇＡ、ＩｇＭ、Ｃ３、Ｃ４近似参考值,ＡＮＡ抗体、ｄｓＤＮＡ抗体滴度下降或转阴,ＥＮＡ抗体及淋巴细胞转化率无明显变化。结论：     

系统性红斑狼疮患者血清泌乳素水平的研究

目的探讨泌乳素（PILL）与系统性红斑狼疮（SLE）的关系。方法检测91例SLE患者与30例健康成人血清PILL水平。结果SLE患者血清PILL水平明显高于正常对照组，且活动期患者PILL水平显著高于静止期患者，PILL水平与抗ds-DNA水平呈正相关。活动期狼疮性肾炎（LN）患者血清PILL水平显著高于静止期患者，PILL水平与抗ds-DNA水平呈正相关。结论SLE患者血清PILL水平与病情活动相关，可将PILL作为判断SLE病情活动性的指标之一；PRL在SLE发病中可能起一定的作用。