Influence of C4 null genes on infection with human immunodeficiency virus

The hypothesis that complement is important in the host response to human immunodeficiency virus (HIV) was tested. Complement C4 and Bf allotypes were determined in 26 patients who fulfilled the diagnostic criteria for persistent generalised lymphadenopathy due to HIV, 72 homosexuals who were negative for antibody to HIV, and 185 control subjects drawn from the local population. HLA-A, B, and DR were also typed and the phenotypes examined for the presence of supratypes and C4BQ0. Eleven patients (42%) had C4B null alleles compared with only 13 (18%) homosexuals who were negative for antibody and 28 (15%) controls. From estimates of gene frequencies the difference between the patients with lymphadenopathy and the controls was significant after conservative correction. In the patients only a minority (six) of the C4B null alleles were contained within ancestral haplotypes. Together with the fact that C4 null alleles result in partial deficiency of C4, this finding suggests that products of complement genes are important in infection with HIV or its consequences, or both. A role is proposed for complement and Fc receptors.     

系统性红斑狼疮C4零基因对C4活性的影响

目的 探讨系统性红斑狼疮（ＳＬＥ）Ｃ４零基因的存在对Ｃ４活性的影响４,方法 采用国际参考实验室的方法及计算机凝固图像光密度分析系统检测４５例广东籍汉族人ＳＬＥ患者Ｃ４零基因,同时用氨溶血法检测这些患者血清中补体Ｃ４活性。结果 含Ｃ４零基因的ＳＬＥ患者血清中补体Ｃ４活性低下不含Ｃ４零基因患者的Ｃ４活性（Ｐ〈０．０１）。结论 ＳＬＥＣ４零基因的存在以地Ｃ４活性有影响,Ｃ４零基因能引起ＳＬＥ患者血清中补     

Correlation between Systemic Lupus Erythematosus Disease Activity Index,C3, C4 and Anti-dsDNA Antibodies

Background

Therapeutic decisions in systemic lupus erythematosus (SLE) are based on the disease activity and nature of organ involvement. There are various clinical and laboratory methods to assess the lupus flares.

Methods

Fifty one SLE patients with active disease (lupus flare) were studied. Systemic lupus erythematosus disease activity index (SLEDAI), C3, C4 and anti-double stranded DNA levels were estimated and repeated monthly till remission. After remission these tests were done three monthly. Values of serological parameters were then correlated with SLEDAI score.

Result

Thirteen (25.4%) patients had predominantly renal involvement while 38 (74.6%) patients had non-renal affliction. Musculoskeletal and mucocutaneous symptoms were the commonest features of lupus flare (90%). It was observed that 12 out of 13 (92.3%) patients with active renal involvement had low C3 levels and 11 (84.6%) had low C4 levels. The anti-dsDNA levels were elevated in all patients with predominant renal flare. In non-renal flare anti-dsDNA titre was raised only in 35% cases. Low C3 and C4 levels were noticed in 43% and 53% of non-renal flares respectively. Significant positive correlation was noticed between SLEDAI score and anti-dsDNA levels (0.01 level two-tailed prediction) and a significant negative correlation was observed with SLEDAI and C3, C4 levels (0.01 and 0.05 levels, two-tailed prediction) in our patients. On subgroup analysis it was noticed that this correlation is stronger for renal lupus. Negative correlation of SLEDAI and complement levels was not observed in non-renal flares.

Conclusion

Calculation of SLEDAI is a vital clinical tool for assessment of SLE patients. Serial estimation of anti-dsDNA titre, C3 and C4 levels help us diagnose lupus flare and make appropriate therapeutic decisions in patients with high SLEDAI score.Key Words: Systemic lupus erythematosus, Lupus flare, Complement, Anti-dsDNA     

系统性红斑狼疮免疫检查研究

目的:探讨临床上系统性红斑狼疮患者血清免疫检查指标和意义.方法:选择我院2009年1月至2010年10月收治的系统性红斑狼疮患者36例,临床常规应用甲基强的松龙,测定治疗前后血清检查抗核抗体、抗双链DNA抗体、免疫球蛋白和补体3水平、肿瘤坏死因子-α和白介素-6含量.与同期体检健康人群血清指标进行比较.结果:系统性红斑...     

Sequential bilateral central retinal artery occlusion as the primary manifestation of systemic lupus erythematosus

Bilateral central retinal artery occlusion (CRAO) has been rarely reported as the primary manifestation in patients with systemic lupus erythematosus (SLE). The severe retinal vaso-occlusive diseases usually cause devastating and permanent damage to visual function in spite of vigorous treatment. A 42-year-old Chinese woman presented with abrupt bilateral vision loss. The diagnosis of bilateral CRAO was suggested by the ocular presentation and fluorescein angiography. Laboratory studies showed positive results of antinuclear antibody, anti-Ro/SSA anti-La/SSB; decreased levels of C3, C4 complement and normal levels of antiphospholipides antibodies (APAs). Her visual acuity deteriorated despite systemic steroid and immunosuppressant treatment. Severe vaso-occlusive retinopathy may be an earlier manifestation of SLE without elevated level of APAs.

     

免疫组织化学方法检测皮损组织中C3d,C4d,IgG,IgG4 及CD123表达在诊断自身免疫性皮肤病中的应用价值

目的：探讨免疫组织化学方法检测皮损组织中C3d，C4d，IgG，IgG4及CD123表达在诊断自身免疫性皮 肤病中的应用价值。方法：采用免疫组织化学方法检测27例红斑狼疮(其中8例盘状红斑狼疮、4例亚急性皮肤型红斑 狼疮、15例系统性红斑狼疮)、15例皮肌炎、15例大疱性类天疱疮、15例天疱疮皮损组织石蜡切片中的C3d，C4d， IgG，IgG4及CD123表达情况；比较免疫组织化学染色与直接免疫荧光检测在红斑狼疮、大疱性类天疱疮、天疱疮皮 损组织中上述5种抗体的阳性率。结果：红斑狼疮组皮损基底膜带的C3d，C4d阳性率分别为85.2%，51.9%，皮肌炎 组C3d，C4d阳性率分别为40%，0；红斑狼疮组皮损组织中C3d，C4d表达水平均明显高于皮肌炎组(P<0.05)。红斑狼 疮组皮损组织中CD123蛋白的表达水平显著高于皮肌炎组(P<0.05)。大疱性类天疱疮组皮损基底膜带的C3d，C4d阳 性率分别为100%，86.7%，天疱疮组角质形成细胞间的C3d，C4d阳性率分别为100%，60%。天疱疮组皮损真皮内的 IgG，IgG4表达水平明显高于大疱性类天疱疮组(P<0.05)，且天疱疮组IgG4/IgG明显高于大疱性类天疱疮组(P<0.05)。 结论：免疫组织化学检测皮损组织中的C3d，C4d在红斑狼疮、大疱性类天疱疮和天疱疮中有重要的诊断价值，在某 些情况下可能作为替代直接免疫荧光的诊断工具。CD123表达对于红斑狼疮的鉴别诊断有一定的临床意义，IgG4和 IgG对于天疱疮有辅助诊断意义。     

血清C1q检测在系统性红斑狼疮疾病活动性判断及狼疮肾炎诊断中的价值

目的  探讨系统性红斑狼疮（SLE）患者血清C1q水平变化对SLE疾病活动性判断及狼疮肾炎（LN）的诊断意义。方法  150例研究对象,根据临床资料,分为SLE组（60例）、其他风湿疾病组（30例）、其他肾脏疾病组（30例）及正常对照组（30例）4组,其中SLE组包括33例LN患者和27例非LN患者。采用免疫透射比浊法测定各组血清C1q水平,并与其他SLE活动性指标进行相关性分析。结果  ①SLE组的血清C1q水平低于其他风湿性疾病组、其他肾脏疾病组及正常对照组（F =41.428,P =0.000）,其中LN组的血清C1q水平低于非LN组（t =-4.262,P =0.000）,SLE病情活动期患者C1q水平低于病情稳定期患者（t =-5.159,P =0.000）。②在SLE组中C1q诊断LN的敏感性为66.7%,特异性为59.3%。工作特征曲线的曲线下面积为0.717。③相关分析表明,SLE患者血清C1q水平与C3、C4呈正相关,与SLE疾病活动指数积分呈负相关（r=0.593、0.448和-0.589,P =0.000）。结论  血清C1q不仅有助于SLE及LN的诊断,且对SLE的病情评估及疗效判断具有重要参考价值。

     

湖南汉族群体HLA-DR2等位基因多态性与系统性红斑狼疮的相关性研究

以HLA DRB基因类扩增为参照 ,通过HLA DR2组特异性扩增确定HLA DR2携带者 ,PCR/SSP作亚型分型 ,并用银染PCR/SSCP分析HLA DR2等位基因第二外显子单链构像 ,调查湖南地区汉族群体SLE(系统性红斑狼疮 )患者 5 8例和健康对照 5 9例HLA DR2等位基因分布。结果示 ,HLA DR2与SLE相关 (RR =2 .71,P <0 .0 1) ,HLA DRB1 15 0 1为疾病相关等位基因 (RR =3 .10 ,Pc <0 .0 5 ) ,该群体中检出的另外两种亚型DRB1 15 0 2 ,160 2在两组间频率分布差异无显著性。此外 ,PCR/SSCP分析表明湖南汉族HLA DR2等位基因在第二外显子内不存在其他序列变异。     

IL-18基因105A/C多态性与长江以南汉族人群系统红斑狼疮(SLE)的关联性

 目的  探讨IL-18(interleukin-18)基因105A/C多态性与中国长江以南汉族人群系统性红斑狼疮(systemic lupus erythematosus,SLE)易感性之间的关系。方法  采用病例对照研究设计,收集病例对照各193例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对IL-18基因105位点进行基因分型,在不同的遗传模式下分析105位点基因多态性与SLE的相关性,用χ2检验分析105A/C多态性与SLE临床表型间的相关性。 结果  IL-18基因105位点A等位基因在两组人群中的分布差异有统计学意义(OR=1.815,95% CI=1.151-2.863),在相加和隐性模型下也发现105A/C多态性与SLE有关(相加:OR=1.828,95% CI=1.152-2.900;隐性:OR=1.855,95% CI=1.131-3.044),且调整年龄、性别等因素后,在两种模型下的相关性仍然存在(相加:OR=1.987,95% CI=1.181-3.343;隐性:OR=1.960,95% CI=1.111-3.456)。此外,本研究显示补体C3C4降低患者A等位基因的频率上升(OR=1.737,95% CI=1.001-3.014),但经Bonferroni校正后差异不具有统计学意义( Pcorr = 0.336)。 结论  在中国长江以南汉族人群中IL-18基因105A/C多态性可能与SLE易感性有关,且A等位基因对SLE可能有危险性效应。     

中国广东汉族人C4、Bf多态性及其补体单倍型研究

目的 探讨广东汉族人C4、Bf遗传多态性及其构成的补体单倍型频率。方法 用琼脂糖高压电泳及免疫固定的方法对广东正常汉族家系144条染色体作了属于HLA-Ⅲ的Bf、CA、C4B的遗传多态性及其构成的补体单倍型检测与分析。结果 共发现13个补体单倍型，居前4位者为S32、S31、S42、F42，其中有4个单体型呈高度连锁不平衡。表型以BFS(0、8542)、C4A3(0、7291)、CA(0、2188)、C4B2(0、5937)、C4B1(0、3542)最常见。结论广东汉族C4、Bf多态性及其构成的补体单倍型有自己的遗传背景。     

Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis.     

系统性红斑狼疮患者血脂水平与肾脏并发症相关性探究

目的：探讨系统性红斑狼疮患者血脂水平与肾脏并发症的相关性及意义。方法：收集系统红斑狼疮患者121例,根据是否伴有肾脏并发症分为甲组（患有狼疮性肾炎）42例和乙组（未患有狼疮性肾炎）79例,另选取60例健康体检者作为对照组,检测三组患者血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDLC）、低密度脂蛋白（LDLC）水平,SPSS19.0统计学软件分析上述指标之间的差异,分析与肾脏疾病进展的相关性。结果：甲组 TC, TG,LDLC 含量高于对照组,HDLC 含量低于对照组;乙组与对照组 TC、TG、LDLC、HDLC 含量差异无统计学意义;甲组 TC,TG 含量高于乙组,HDLC 含量低于乙组,TG,TC,LDLC 是系统性红斑狼疮患者并发肾炎的危险因素。结论：系统性红斑狼疮患者血脂水平与肾脏并发症的发生密切相关,TG、TC、LDLC 水平异常增高是系统性红斑狼疮患者并发肾炎的独立危险因素。     

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

OBJECTIVE: To investigate the possible association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) promoter -1722 polymorphism with systemic lupus erythematosus (SLE) in the population in southern China. METHODS: A total of 103 SLE patients (13 males and 90 females with an average age of 33.63+/-12.58 years) diagnosed according to the SLE diagnostic criteria of the American College of Rheumatology revised in 1982 and 110 healthy ethnically matched controls (21 males and 89 females with an average age of 27.49+/-8.60 years), all from southern China, were enrolled in the study. DNA was extracted from EDTA-treated blood samples according to the standard isolation procedure. The restriction fragment length polymorphism-polymerase chain reaction was used to analyze CTLA-4 promoter-1722 polymorphism in SLE patients and healthy controls. RESULTS: Compared with the controls, the SLE patients had higher frequencies of TC genotype (42% vs 58%, P<0.05) and lower frequency of CC genotype (25% vs 15%, P<0.05). There were no significant differences in the frequencies of TT genotype, alleles and phenotypes between SLE patients and controls; however, significant differences in the frequencies of TT genotype and alleles of CTLA-4 promoter -1722 were found among different races (P<0.05). CONCLUSION: CTLA-4 promoter -1722 polymorphism appears to be associated with SLE susceptibility in southern Chinese population.     

系统性红斑狼疮患者血清抗DNA酶B抗体检测的临床意义

目的探讨系统性红斑狼疮（SLE）患者血清中抗DNA酶B抗体滴度测定的临床意义。方法采用微量滴定法分别测定了SLE患者77例和正常人43例血清中的抗DNA酶B抗体滴度，并结合临床资料进行对比分析。结果SLE组抗DNA酶B抗体的阳性率为76．6％；对照组55．8％，2组差异有统计学意义（X^2=5．60，P=0．018）。血清抗DNA酶B抗体阳性的SLE患者发热、关节炎、肾损害的发生率均显著增高（X^2依次为4．084，5．502，8．606，P分别为0．043，0．019，0．003）；血清CRP增高，补体C3降低以及抗ds-DNA抗体、抗核小体抗体阳性者亦显著增多（X^2依次为4．247，9．899，4．987，6．512，P分别为0．039，0．002，0．026，0．011）。SLE活动期和非活动期抗DNA酶B抗体的阳性率分别为67．8％和16．7％，活动期患者显著为高（X^2=14．62，P=0．000）。结论SLE患者中A组溶血性链球菌（GAS）感染发生率高于正常人，SLE合并肾损害时需要排除GAS感染。GAS感染与SLE病情活动有一定的关系。     

山东省急性淋巴细胞白血病患儿HLA-A、B、DRB1等位基因多态性研究

目的:研究山东省汉族急性淋巴细胞性白血病(ALL)患儿与等位基因HLA-A、B、DRB1的多态性的遗传关联。方法:采用聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSO)方法,对197例ALL患儿和5841例健康脐带血样本等位基因HLA-A、B、DRB1多态性进行研究。结果:在等位基因HLA-A、B、DRB1中,ALL患儿的A11和A24;B40、B15、B56、B67和B27;DR9、DR12、DR14和DR16等基因的基因频率显著高于正常人群(P<0.01)。而HLA-B48、DR7和DR15等基因的基因频率显著下降(P<0.05)。结论:基因HLA-A11、A24、B40、B15、B56、B67、B27、DR9、DR12、DR14、DR16对ALL患儿有遗传易感作用,尤其是B40与ALL具有强相关性;而基因HLA-B48、DR7、DR15等对ALL患儿有遗传拮抗作用。     

系统性红斑狼疮血中IL-18的变化及临床意义

目的:探讨系统性红斑狼疮(SLE)患者血中白细胞介素18(IL-18)的变化及临床意义.方法:采用双抗体夹心(ELISA)法对SLE患者及正常对照者血中IL-18进行测定.结果:活动期SLE血中IL-18明显增高,SLE伴尿常规明显异常者IL-18增高最明显,IL-18水平与尿蛋白的增加呈正相关,与SLE活动指标中抗ds-DNA呈正相关,与C3、C4变化呈负相关.结论:IL-18通过直接或间接影响某些免疫过程参与SLE的病理损伤过程.     

神经精神性狼疮脑电图及临床分析

目的通过脑电图检测和临床转归，观察甲基泼尼松龙和环磷酰胺单剂及联合冲击治疗神经精神性狼疮的疗效和不良反应。方法36例神经精神性狼疮患者随机分为3组，分别应用甲基泼尼松龙（A组）、环磷酰胺（B组）、甲基泼尼松龙联合环磷酰胺（c组）冲击治疗；动态观察脑电图改变、SLE疾病活动指数、血清补体C3、IgG含量及ANA、抗ds—DNA抗体、抗Sm抗体的转阴率，评估其疗效和不良反应。结果（1）治疗6个月后显效的15例患者脑电图完全恢复正常者13例；好转的11例患者中4例恢复正常；无效的10例患者轻度异常2例，中度异常4例，重度异常2例。（2）治疗后1、6个月后3组SLE疾病活动指数降低、血清补体C3、IgG含量及ANA、抗ds—DNA抗体、抗sm抗体的转阴率均增高，较治疗前有显著性差异（均P〈0．01），而且C组的上述指标变化显著优于A、B两组（P〈0．05或0．01）；（3）治疗1、6个月后，C组显效率（40％／60％）明显高于A组（14％／28％）、B组（17％／42％），P〈0．05或0．01；A、B两组显效率无显著性差异（P〉0．05）。结论甲基泼尼松龙和环磷酰胺联合冲击治疗神经精神性狼疮疗效优于单剂冲击治疗．脑电图改变与临床改变呈正相关。     

THE POLYMORPHISMS OF HLA-DR AND TNF B LOCI IN NORTHERN CHINESE HAN NATIONALITY AND SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS

With the aid of methods of polymerase chain reaction / sequence specific primers (PCR/SSP) and polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP), the allelic polymorphism of HLA-DR and TNFB loci and susceptibility to systemic lupus erythematosus (SLE) in northern Chinese Han nationality were studied. The genetic analysis of 51 patients with SLE and 106 healthy controls indicated that frequencies of DR2 and DR3 alleles were significantly increased in SLE patients(P< 0.05 and <0. 005, relative risks of 1.77 and 4.01 respectively), which represent candidate susceptible genes or useful marker for SLE. The frequency of DR5 was found to decrease in SLE patients compared with control population (P<0. 025,relative risk = 0. 38). It might be an antagonistic or protective allelle or a marker for such allele. Analysis of 51 patients with SLE and 80 healthy control also revealed that the frequency of TNFB' 2 allele was significantly increased(P<0. 05,RR= 1. 70). Therefore TNFB' 2 gene ma     

系统性红斑狼疮辨证分型与可溶性粘附分子之间关系探讨

[目的]探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)辨证分型的实质,寻求SLE辨证分型的实验依据。[方法]采用酶联免疫吸附法(ELISA法)测定SLE患者中肝肾阴虚型、热毒炽盛型的可溶性细胞间粘附分子-1(solubleintercellular adhesion molecule-1,sICAM-1)、可溶性血管细胞粘附分子-1(soluble vascular cell adhesion molecule-1,sVCAM-1)血清水平的变化,并与正常对照组比较;分析不同证型两指标之间及其与C反应蛋白(CRP)、补体3(C3)、补体4(C4)含量的相关性。[结果]肝肾阴虚型和热毒炽盛型的SLE患者血清sICAM-1、sVCAM-1含量高于正常对照组(P<0.01),且热毒炽盛型的血清sVCAM-1含量高于肝肾阴虚型(P<0.05);SLE患者的sICAM-1与sVCAM-1有较好的相关性。[结论]血清sICAM-1与sVCAM-1含量测定对SLE的诊断和辨证有一定参考价值。     

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。