中国人SLE患者N—乙酰化转移酶的研究

本文对３２例系统性红斑狼疮及２５例类风温性关节炎进行了Ｎ－乙酰化转移酶多态现象和基因频率的研究。结果显示：ＳＬＥ中６例为慢反应型，基因频率Ｒ为０．５６７０，γ为０．４３３０；ＲＡ中１８例为慢反应型，基因频率Ｒ为０．１５１５，ｒ为０．８４８５。ＳＬＥ组与正常组无差异，ＲＡ组与ＳＬＥ组及正常组相比皆有显著性差异。     

N—乙酰化转移酶基因多态与肝癌遗传易感性的研究

为探讨Ｎ－乙酰化转移酶（ＮＡＴ）基因多态与肝癌遗传易感性的关系，应用ＰＣＲ、ＡＳＰＣＲ和ＲＦＬＰ，对６５例肝癌患者和１０６例健康对照进行了研究。结果表明，病例组慢型基因频率为７０．７７％，对照组为５２．８３％，两者差异显著（Ｐ＝０．００１）。ＯＲ值为２．１６，ＥＦ值为０．３８０１。提示携带慢型基因者患肝癌的危险性增加１．１６倍，由慢型基因所致的肝癌病例占人群中全部肝癌病例的３８．０１％。病例组基因型Ｆ１／Ｆ１、Ｆ１／Ｓ和Ｓ／Ｓ的频率分别为９．２３％、４０．００％和５０．７７％，对照组则分别为２２．６４％、４９．０６％和２８．３０％，两者差异显著（Ｐ＝０．００５６）。ＯＲ值分别为１．００、２．００和４．４０，存在剂量反应关系。发现４个新的慢型基因亚型，其点突变组合为３４１／５９０、５９０／８０３、２８２／３４１／５９０、２８２／３４１，将其暂命名为Ｓ９，Ｓ１０，Ｓ１１和Ｓ１２。     

SLE及RA患者的红细胞免疫功能

红细胞表面具有１型补体受体（ＣＲ１）、Ⅲ型补体受体ＣＲ３、ＣＤ５８、ＣＤ５９、ＩＬ－８受体和ＳＯＤ酶等。人类红细胞膜上的ＣＲ１为糖肽，其主要配体是Ｃ３ｂ、Ｃ４ｂ、ｉＣ３ｂ和ｉＣ４ｂ。Ｃ３ｂ受体具有免疫粘附功能。人体清除循环免疫复合物（ＣＩＣ）的功能主要是红细胞，其清除作用较具有免疫和防御机能的白细胞高５００～１０００倍。因此，红细胞免疫粘附（ＲＣＩＡ）功能的变化与疾病的关系日益受到重视。我们采用酵母菌花环试验，测定了２７例ＳＬＥ和３１例ＲＡ患者外周血ＲＢＣ－Ｃ３ｂＲ花环率及ＲＢＣ－ＩＣＲ花环率，…     

CD137在SLE和RA病人外周血T细胞上的表达特点及意义

ＣＤ137是一种新的Ｔ细胞共刺激分子。最近研究显示 ,ＣＤ137和ＣＤ137配体 (ＣＤ137Ｌ)可能为ＣＤ2 8/Ｂ7之外的另一对关键的共刺激信号分子 ,开始引起人们的注意。目前国外有关ＣＤ137的研究主要来自鼠 ,在人方面的研究尚少 (至 1999年 9月仅有 14篇报道 ) ,许多问题尚不清楚。国外虽已研究了ＣＤ137在正常人Ｔ细胞表达 ,但有关ＣＤ137在自身免疫病病人的表达特点尚无报道。我们在研究了ＣＤ137在正常人外周血Ｔ细胞表达的基础上 ,进一步分析了ＣＤ137在系统性红斑狼疮 (ＳＬＥ)和类风湿性关节炎(ＲＡ)病人Ｔ细胞的表达特点。材料和方法材…     

RA和SLE患者中剪接体自身反应的初步研究

在研究类风湿关节炎（ＲＡ）特异性诊断方法的过程中，发现ＲＡ３３抗体（Ａ２ｈｎＲＮＰ抗体）与ＲＮＰ抗体（Ｕ１ｓｎＲＮＰ抗体）的出现密切相关。剪接体的一部分可作为自身抗原诱发自身免疫反应，部分ＲＡ病人对Ａ２ｈｎＲＮＰ起自身免疫反应，而部分ＳＬＥ病人可对ｓｎＲＮＰ和ｈｎＲＮＰ反应，两种疾病都是典型的剪接体自身反应。这表明ＲＡ和ＳＬＥ在发病机理上既有区别又有联系，而剪接体在发病过程中起重要作用。     

SLE、RA患者血清sICAM—1和FTM水平的变化及其临床意义

系统性红斑狼疮 (ＳＬＥ)和类风湿性关节炎 (ＲＡ)是多系统受累的自身免疫性疾病 (ａｕｔｏｉｍｍｕｎｅｄｉｓｅａｓｅｓ,ＡＩＤ) ,其免疫特征是 ,Ｔ细胞活化增加 ,Ｂ细胞多克隆活化并产生多种自身抗体 ,但其发病机制尚不清楚。可溶性细胞间黏附分子 1(ｓｏｌｕｂｌｅｉｎｔｅｒｃｅｌｌｕｌａｒａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅｓ 1,ｓＩＣＡＭ 1) ,是表达于内皮细胞和其他抗原递呈细胞上的ＩＣＡＭ 1脱落于血液中的可溶性形式 ,属于免疫球蛋白超家族中的成员 ,为一种表面跨膜蛋白抗原。内皮细胞表面细胞黏附分子的异常表达是内皮细胞损…     

SLE、RA患者血清sICAM-1和PTM水平的变化及其临床意义

系统性红斑狼疮(SLE)和类风湿性关节炎(RA)是多系统受累的自身免疫性疾病(aut oimmune diseases,AID),其免疫特征是,T细胞活化增加,B细胞多克隆活化并产生多种自身抗体,但其发病机制尚不清楚.可溶性细胞间黏附分子-1(soluble intercellular ad hesion molecules-1,sICAM-1),是表达于内皮细胞和其他抗原递呈细胞上的ICAM-1脱落于血液中的可溶性形式,属于免疫球蛋白超家族中的成员,为一种表面跨膜蛋白抗原.内皮细胞表面细胞黏附分子的异常表达是内皮细胞损伤的早期变化[1].     

可溶性补体受体2在风湿免疫病患者血清中的变化及意义

目的:探讨风湿免疫病患者血清中可溶性补体受体2(sCR2)的变化及意义.方法:采用ELISA法检测31例类风湿性关节炎(RA)、 18例系统性红斑狼疮(SLE)和20例健康体检者血清中可溶性补体受体2的浓度.结果:RA和SLE患者sCR2水平均明显低于健康体检者(P＜0.01), RA和SLE患者间无统计学意义(P＞0.05).sCR2与年龄和性别无关, 在RA中与RF无关, 在SLE中与C3无关, 在RA 活动期明显低于非活动期(P＜0.05).结论:在自身免疫病中由于疾病本身导致了血清中sCR2的减少, 疾病的活动程度可能与sCR2血清水平有一定关系.     

lncRNA与自身免疫病关系的研究进展

长链非编码RNA(long noncoding RNA,lncRNA)是长度超过200nt非编码蛋白的ncRNA,参与调节生物学过程如基因转录、蛋白合成。研究发现lncRNA可通过与相关的DNA、RNA和蛋白质相互作用调节基因表达,通过各种机制与人类疾病密切相关,尤其与系统性红斑狼疮、类风湿关节炎等多种自身免疫病相关。了解它们之间的关系,有助于我们进一步了解自身免疫病的分子机制,为开发治疗药物提供帮助。本文综述lncRNA的分类、结构和作用机制,以及近年来关于lncRNA参与自身免疫病发生发展的研究进展。     

SLE患者几种细胞因子水平变化的观察

<正>系统性红斑狼疮(SLE)病人存在着一系列细胞因子的异常.而在这些异常的细胞因子之间,是否有内在的联系,是一个令人感兴趣的问题.我们对不同病情的SLE患者的几种细胞因子之间的相互联系作了一些初步的比较观察.1 对象和方法1.1 研究对象 活动期SLE病人系在上海市仁济医院和上海市瑞金医院就医的患者,均为女性,年令18～54岁.符合1982年美国风湿病学会诊断标准.缓解期SLE病人系上述医院门诊随访SLE患者,均为女性,年龄18～54岁.正常对照为年龄与上述两组SLE患者接近的正常女性.     

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility

BackgroundMicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.MethodsA PubMed database search was conducted during August 2013 to identify case–control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.ResultsOur meta-analysis of six case–control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI = 0.642–1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR = 0.911, 95% CI = 0.710–1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR = 0.616, 95% CI = 0.384–0.981, (T vs. C allele) and OR = 0.386, 95% CI = 0.226–0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR = 1.263, 95% CI = 1.136–1.405, G vs. A allele).ConclusionsThe present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.     

Evaluation and management of systemic lupus erythematosus and rheumatoid arthritis during pregnancy

Women of childbearing age are at risk for developing systemic rheumatic diseases. Pregnancy can be challenging to manage in patients with rheumatic diseases for a variety of reasons including the impact of physiological and immunological changes of pregnancy on underlying disease activity, the varied presentation of rheumatic disease during pregnancy, and the limited treatment options. Previously, patients with rheumatic disease were often advised against pregnancy due to concerns of increased maternal and fetal morbidity and mortality. However, recent advancements in the understanding of the interaction between pregnancy and rheumatic disease have changed how we counsel patients. Patients with rheumatic disease can have successful pregnancy outcomes, particularly when a collaborative approach between the rheumatologist and obstetrician is applied. This review aims to discuss the effect of pregnancy on patients with the most common rheumatic diseases, the effect of these diseases on the pregnancy itself, and the management of these patients during pregnancy.     

Combined steroid-cyclosporin treatment of chronic autoimmune diseases

Summary Twenty-one patients suffering from different autoimmune diseases (14 from systemic lupus erythematosus, 4 from rheumatoid arthritis, one from Sjögren's syndrome, one from systemic hypersensitivity vasculitis, and one from diffuse proliferative glomerulonephritis) were treated with a combined immuno-suppressive regimen. Cyclosporin was given at a dose of 5 mg/kg/day together with steroids. In addition, the rheumatoid arthritis patients also received methotrexate. In all patients a kidney biopsy was performed after a treatment period of 17 to 42 months (mean duration 21.7 months). The cumulative cyclosporin dose at the time of biopsy varied from 1.071 to 4.587 mg/kg. Patients suffering from systemic lupus erythematosus and rheumatoid arthritis were assessed according to a scoring system set up for this purpose. The combined therapy proved useful in these patients as reflected in the diminution of the respective activity scores, improvement of kidney function, and diminution of proteinuria. Histological examination of the kidney biopsy specimens showed only minimal activity in patients with systemic lupus erythematosus. No unequivocal signs of renal toxicity could be detected. In the last group, the condition of the patient with Sjögren's syndrome was stabilized and the patient with systemic vasculitis improved clinically. Neither patient had signs of kidney lesions. The patient with diffuse proliferative glomerulonephritis, in whom kidney biopsy was performed before and after treatment, showed improvement of kidney function, diminution of proteinuria, and diminution of inflammatory activity within the kidney, and no signs of cyclosporin toxicity.Abbreviations CyA Cyclosporin - MTX Methotrexate - NSAID Nonsteroidal antiinflammatory drugs - RA Rheumatoid arthritis - SLE Systemic lupus erythematosus - TFA index Index of extent of tubular atrophy, intersitital fibrosis, and arteriolopathy     

Sexual disparities in the incidence and course of SLE and RA

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) disproportionately affect females compared to males, with female to male prevalence ratios of 7–9:1 for SLE and 2–3:1 for RA. Interestingly, epidemiologic studies indicate that men that develop SLE may have more morbidity than women, but the same is not true for RA. Given the sex and age bias of SLE and RA, sex hormones may influence the pathogenesis of these diseases. However, the ways in which, and to what degree, sex hormones affect disease incidence and severity remain unclear and is the topic of ongoing research. Recent findings have implicated interactions between sex hormones, the immune system, genetic factors, and epigenetic modifications in influencing SLE and RA disease activity. This article reviews current hypotheses regarding the potential impact of sex hormones and genetics on disease pathogenesis, incidence, and severity of SLE and RA.     

Differential generation of chemiluminescence — detectable oxygen radicals by normal polymorphonuclear leukocytes challenged with sera from systemic lupus erythematosus and rheumatoid arthritis patients

Summary The generation of chemiluminescence (CL)-detectable oxygen radicals by normal human polymorphonuclear leukocytes (PMN) after challenging with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) sera is described. CL was measured in a luminol-dependent assay and referred to a standard obtained when preformed immune complexes (Ic) (human tetanus toxoid-antitoxoid Ic resuspended in normal pooled serum) were tested on PMN. Normal sera gave rise to CL activity by PMN between 0% and 50% of the standard Ic (mean±standard error of the mean (SEM): 20.7±4.8). Sera from SLE and RA patients induced strikingly different biological effects on PMN. SLE sera generally induced a high CL-detectable generation of oxygen metabolites which may be causally related to the intense tissue damage (vasculitis) frequently observed in this disease. In contrast to SLE, RA sera induced a CL-detectable respiratory burst by PMN that was included in the normal range. Thus, the biological effects of these sera in terms of stimulation of toxic oxygen radical generation by phagocytes are quite different. This generation of oxygen radicals might reflect a different clearance of circulating Ic by PMN in SLE and RA disease.Abbreviations CL Chemiluminescence - PMN Polymorphonuclear Leukocytes - SLE Systemic Lupus Erythematosus - RA Rheumatoid Arthritis - Ic immune complexes - TAT tetanus-antitetanus toxoid - TAT-S tetanus-antitetanus toxoid resuspended in pooled, non-inactivated human serum - SEM standard error for the mean - EHM Eagle-Hepes-Medium - PBS phosphate-buffered-saline - RF rheumatoid factor - SPA staphylococcal protein A - ANA antinuclear antibodies - KD kilodaltons - Ag antigen     

Chloroquine has not disappeared

Chloroquine (CHQ), an antimalarial, is also used as an anti-inflammatory drug for systemic lupus erythematosus and rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) reduces the frequency of organ involvement and disease flares, and relieves skin and joint symptoms. CHQ reduces the immunologically-mediated inflammation of the joints. HCQ and combination therapies have a significant benefit on synovitis, pain and physical disability on RA. We advocate the investment of resistance Plasmodium prevalence determinations in countries beset by malaria, and to match thereafter the quantity of persons administered CHQ. Follow-up investigations are essential to diagnose and prevent visual damage.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Genetic Studies of Human Lupus in Families

Systemic lupus erythematosus (SLE) is a complex multigenic disease in which the contributing genetic systems are being rapidly identified. Most of the currently recognized genes have been discovered from case-control association studies, but, increasingly, family linkage studies are being employed to confirm previous genetic associations, to examine their relative contributions, and to identify new susceptibility loci. Most of the loci identified thus far appear to contribute only modest effects on susceptibility overall but rather influence more strongly disease expression and/or severity. MHC class II alleles, for example, seem to show only weak linkage to SLE itself but instead mediate specific T cell driven pathogenic autoantibodies which produce many of the clinical disease features, similar to their effects in many other autoimmune diseases. On the other hand, complete and partial hereditary deficiencies of early complement components are more lupus-specific. Homozygous complement deficiencies, while powerful risk factors, are rare causes of lupus and heterozygous deficiencies exert only modest effects on susceptibility. Other genes, such as low-binding IgG Fc receptor alleles (FcγIIa and FcγIIIa), appear to promote nephritis by modifying the efficiency of immune complex clearance. A variety of cytokine genes appear also to promote severity, including those for TNFα, IL-10, IL1 receptor antagonist, and perhaps others (IL-6, IL-4 and TNFα receptor). Family studies and recent genome-wide scans in lupus and other autoimmune diseases support the likelihood that some susceptibility loci, as yet unidentified, predispose to several or many autoimmune diseases. Only thorough the identification and elucidation of function of these many genes is the pathogenic picture of lupus likely to be complete.