强直性脊柱炎患者细胞微粒的表达及临床意义

目的:研究细胞微粒、血小板微粒（PMPs）、CD41a +CD62P +PMPs在AS患者中表达水平及临床意义。 方法:收集47例确诊的AS患者和15名健康对照组的空腹静脉血并检测ESR、CRP,计算BASDAI评分。采用流式细胞术（FCM）检测AS患者和健康对照组细胞微粒、PMPs、...     

强直性脊柱炎患者HLA-B27的表达及其临床意义

强直性脊柱炎（ankylosing spondylitis,AS）是一种主要累及中轴关节的自身免疫性和慢性进行性炎性疾病。人类白细胞抗原（human leukocyte antigen,HLA）-B27与AS具有明显的关联性。本研究采用微量淋巴细胞毒法（NIH标准）对在我院诊治的98例AS患者外周血中单个核细胞表面的HLA-B27进行检测,并分析其表达情况与临床资料的相关性,报道如下。     

强直性脊柱炎患者骨密度随年龄的变化

目的 采用双能X线吸收法测量强直性脊柱炎患者(AS)不同部位的骨密度(BMD),探讨其与年龄变化的关系,为临床防治AS患者BMD降低提供参考.方法 选取门诊50例符合纽约诊断标准的AS患者,按年龄≤40岁、年龄＞ 40岁分为两组,分别检测其侧位腰椎(L1-L4)、股骨颈、髋关节BMD,以T值≤-1.0定义为BMD降低,包括骨量减少(-2.5＜T＜-1.0)与骨质疏松(T≤-2.5).结果 两组AS患者出现BMD降低的比例均高于正常人,且年龄＞ 40岁组其腰椎BMD减少的比例高于年龄≤40岁组(P＜0.05),而其腰椎平均T值低于年龄≤40岁组(P＜0.05),在股骨颈测得的BMD、骨质疏松比例两组无明显差异(P＞0.05).结论 AS患者早期即可出现骨量减少甚至骨质疏松,随着年龄的增长其侧位腰椎BMD降低明显,骨折风险增大.临床上应当提高对AS合并骨质疏松的警惕,及时予补钙等治疗,提高患者的生活质量.     

强直性脊柱炎患者血清ASO检测及临床意义

目的探讨强直性脊柱炎（AS）患者血清中抗链球菌溶血素O（ASO）的临床意义。方法采用胶乳凝集法测定159例AS患者血清中ASO水平,检测ASO阳性（〉200IU／ml）者（67例）和阴性（≤200IU／ml）者（92例）的白细胞抗原-B27（HLA-B27）、血沉（ESR）、C-反应蛋白（CRP）等实验室指标并记录体温,观察临床症状、体征及影像学分级。结果ASO阳性者发热、ESR、外周关节疼痛、“4”字试验及Schober试验阳性的发生率均显著高于阴性者（P均〈0．05）。影像学表现：骶髂关节炎Ⅱ级和Ⅲ级者明显高于阴性者（P〈0．05）。结论溶血性链球菌感染在AS病情发展中起重要作用,ASO可作为判断AS严重程度和病情活动的重要指标。     

肿瘤坏死因子-α基因启动子376位点基因多态性与强直性脊柱炎的相关性

目的探讨中国汉族人强直性脊柱炎(AS)患者肿瘤坏死因子(TNF)-α基因启动子-376位点基因突变与AS的相关性,及其可能的致病分子生物学机制。方法用等位基因特异性扩增的方法,对164例AS患者和121例正常对照者的TNF-α基因启动子-376G/A单核苷酸多态性(single nucleotide polymorphisms,SNPs)进行基因分型,分析单个位点的等位基因和基因型频率是否与AS相关。结果 TNF-α-376位点的3个基因型频率在AS组中分别为89%、1.2%和9.8%,在对照组中分别为92.6%、0.8%和6.6%,2组之间基因型频率分布比较,差异无显著统计学意义(χ2=1.016,P=0.602);G和A等位基因频率在AS中分别为93.9%和6.1%,在对照组中分别为95.9%和4.1%,2组比较差异无显著统计学意义(χ2=0.721,P=0.346)。结论 TNF-α-376基因多态性与AS不存在显著的相关性,TNF-α-376可能不是AS的易感基因。     

强直性脊柱炎新的疾病活动性指数在中国患者中的应用价值研究

目的 验证新的强直性脊柱炎(AS)疾病活动性指数(ASDAS)在中国的AS患者中的辨别能力,评估其临床应用价值.方法 本研究共纳入AS患者129例,分别为参加依那西普临床试验的活动期AS患者(87例)和使用类克治疗的AS患者(42例).分别以4个ASDAS、毕氏AS疾病活动指数(BASDA1)及患者总体评价来评价患者的疾病活动性水平和治疗效果.计算标准化的均数差(SMD)分析指标的辨别能力,运用Pearson相关分析.两独立样本t检验与一元线性回归进行统计学处理.结果 无论是基线水平还是治疗6周后的变化程度,4个新的ASDAS均与患者总体评价(r=0.56～0.74)、红细胞沉降率(ESR)(r=0.50～0.80)及C反应蛋白(CRP)(r=0.50～0.69)有较好的相关性.4个ASDAS对AS患者的疾病活动性水平及治疗前后病情变化程度的辨别能力均优于BASDA1、患者总体评价、ESR和CRP.4个ASDAS之间差异无统计学意义.结论 新的ASDAS用于评价我国AS患者的疾病活动性和药物疗效有较高的辨别能力,值得临床推广和应用.     

强直性脊柱炎患者生物制剂的优化治疗

目的:评估AS治疗中生物制剂减量的可行性与有效性。方法:对2014年9月至2020年7月的研究进行广泛地系统文献综述,以筛选相关论文和摘要,并应用纳入/排除标准之后,采用结构化提取过程来收集被纳入研究的信息。结果:13/93篇论文被纳入对AS患者生物制剂减量的分析,其中7/13篇采用减少剂量方案,3/13篇采用延长间隔...     

α1抗胰蛋白酶在强直性脊柱炎患者滑膜组织中表达的研究

目的 观察α1抗胰蛋白酶(ATA1)在强直性脊柱炎(AS)滑膜组织中的表达分布,并探讨编码该蛋白的基因对AS的遗传效应.方法 选用8例AS,9例类风湿关节炎(RA)和9例骨关节炎患者关节滑膜样本,用蛋白免疫印迹定量分析ATA1的表达水平,用免疫组织化学法定位ATA1在滑膜组织中表达分布.分别选用32例AS、RA、骨关节炎滑液样本分析ATAl在滑液中的表达水平.选用56例AS血液样本,260例RA和160名健康者样本作对照,用水解探针法对标签单核苷酸多态性位点(SNP)(rs2753934,rs2749531和rs6575424)进行基因分型.采用单因素方差分析、LSD检验和x2检验进行统计分析.结果 与RA、骨关节炎滑膜比较,ATA1在AS滑膜中呈高表达,表达率为100％.同样,ATA1在AS滑液中表达量(1.6±0.6)也高于RA(1.4±0.5)和骨关节炎(1.2±0.5)的表达量(P＜0.05).基因分型发现ATAl SNP与AS和RA无明显关联(P＞0.05).单体型分析没有检测到与AS相关的或与RA相关的单体型.结论 ATA1在AS滑膜组织中高表达,提示ATA1及关节滑膜在AS发病过程中起重要作用.     

强直性脊柱炎患者睡眠质量及相关因素分析

目的 探讨强直性脊柱炎(AS)患者的睡眠质量及影响因素,为提高患者睡眠质量提供依据.方法 采用匹兹堡睡眠质量指数(PSQI)、Zung's抑郁自评量表(SDS)和焦虑自评量表(SAS)及自制-般情况调查表,对318例门诊AS患者进行问卷调查;全部资料使用SPSS 17.7软件包进行统计分析,采用t检验、x2检验、秩和检验及Pearson相关分析.结果 PSQI总分(6.6±3.6)分,睡眠质量差者占35.4％;PSQI得分及检出率均无性别差异;伴睡眠问题与不伴睡眠问题的AS患者之间,晨僵(Z=-3.077,P=0.002)、Bath AS功能指数(BASFI)(Z=-4.766,P=0.000)、Bath AS疾病活动指数(BASDAI)(Z=-6.880,P=0.000)、脊柱夜间痛视觉模拟评分法(VAS)(Z=-6.502,P=0.000)、总体痛VAS(Z=-6.675,P=0.000)、红细胞沉降率(ESR)(Z=-2.370,P=0.018)、C反应蛋白(CRP)(Z=-2.063,P=0.039)差异均有统计学意义(P＜0.05).PSQI总分仅与年龄呈正相关(r=0.165,P=0.003),与性别、年龄(28±8)岁和病程(6±5)年无相关关系(r=0.078,P=0.165;r=0.094,P=0.097).伴有抑郁、焦虑情绪与不伴抑郁、焦虑情绪AS患者的睡眠质量差异有统计学意义(t=-7.613,P=0.000;t=-7.287,P=0.000).结论 AS患者存在睡眠障碍的比例很高,与年龄、抑郁、焦虑情绪以及疾病活动性有密切关系;AS患者的睡眠问题需要引起风湿科医生的重视.     

强直性脊柱炎和类风湿关节炎患者低相对分子质量IgM水平的研究

目的 研究强直性脊柱炎(AS)和类风湿关节炎(RA)患者体内低相对分子质量IgM水平的变化.方法 取AS、RA患者和健康对照人群血清,超滤法分离低相对分子质量IgM,酶联免疫吸附试验测定低相对分子质量IgM比例.采用Mann-Whitney U检验方法进行统计分析.结果 AS和RA患者血清低相对分子质量IgM比例较健康对照明显升高(分别为0.194±0123,0.061±0.026,0.028±0.165);低相对分子质量IgM比例与患者病情活动度无明显相关.结论 低相对分子质量IgM升高可能是AS和RA患者体内体液免疫功能紊乱的表现,但其具体的病理意义尚需进一步研究.

Abstract：

Objective To study the serum levels of low molecule weight IgM (LMW IgM) in ankylosing spondylitis (AS) patients and rheumatoid arthritis (RA) patients and to evaluate the relationship of LMW IgM levels with the disease activities. Methods The levels of LMW IgM and pentameric IgM in AS patients, RA patients and healthy controls were measured with ELISA after separated using ultrafiltration assay. Differences in the percentage of LMW IgM between subject groups were analysed using Mann-Whitney U test. Results The percentages of LMW IgM increased dramatically in AS patients and RA patients compared with healthy controls (0.194 ± 0123, 0.061 ±0.026, 0.028 ±0.165 separately). The LMW IgM percentages were not correlated with the disease activities. Conclusion The increase of LMW IgM indicates humoral immune function abnormality in AS patients and RA. However, the mechanism needs further study.     

A novel gene variation of TNFalpha associated with ankylosing spondylitis: a reconfirmed study

BACKGROUND: A great deal of evidence has shown that non-human leucocyte antigen (HLA)-B27 genes may play crucial roles in the aetiology of ankylosing spondylitis (AS), but there is little evidence of a relationship with tumour necrosis factor (TNF)alpha gene variation. One functional single-nucleotide polymorphism (SNP), -850 C-->T, on the TNFalpha gene promoter region was identified and confirmed to be significantly associated with AS by our recent study. OBJECTIVE: To investigate whether the -850 C-->T SNP is a susceptibility locus for AS or is only a marker linked to potential disease gene loci in a Chinese population. METHODS: Ten common SNPs were selected from nine inflammatory genes covering the right and left flanking regions of the TNFalpha gene, which span a region of about 100 kb on chromosome 6p21.31, and a tag SNP in HCP5 gene was used to examine the linkage between the HLA-B27 and TNFalpha genes. SNPs were genotyped by PCR restriction-fragment length polymorphism (RFLP), allele-specific PCR and restriction site-generating PCR-RFLP for single-base association and linkage disequilibrium (LD). RESULTS: The prevalence of TNFalpha-850 C-->T SNP was significantly different between case and control groups. A specific haplotype covering TNFalpha gene mutant was strongly associated with AS. An LD test showed that a recombination between HLA-B27 and TNFalpha might have taken place. CONCLUSION: The TNFalpha locus was reconfirmed and showed association with susceptibility to AS. It may be independent of HLA-B27. A range of 58 kb covering TNFalpha had strong LD to AS.     

The human immunodeficiency virus (HIV)-type 1 coreceptor CXCR-4 (fusin) is preferentially expressed on the more immature CD34+ hematopoietic stem cells

 In synergy with the CD4 antigen, the chemokine receptor CXCR-4 functions as a coreceptor for T-cell-tropic HIV-1 strains. Using two- and three-color immunofluorescence analysis, we examined the expression of CXCR-4 on CD34+ cells in 21 samples obtained from leukapheresis (LP) products of cancer patients who underwent G-CSF-supported cytotoxic chemotherapy. In addition, eight samples from bone marrow (BM) were obtained. CXCR-4 was expressed on the surface of CD34+ cells from samples of both hematopoietic sources. The mean proportion of CD34+/CXCR-4+ cells from LP products was 1.7-fold greater in comparison with those from bone marrow (65.9±4.1% vs. 37.5±8.6% [±SEM], p<0.05). For an intraindividual comparison, LP products and bone marrow from six patients were obtained on the same day, confirming the significantly greater proportion of CD34 + cells coexpressing CXCR-4 cells in LP products. In order to examine whether the CXCR-4 expression was related to the stage of maturation and differentiation of CD34+ cells, six samples from LP products and four samples from bone marrow were assessed using three-color immunofluorescence analysis. We found that the subset of CD34+/CD38^low and CD34+/HLA-DR^low cells representing a population of more immature progenitor cells were brightly positive for CXCR-4, while there was a decrease in the level of CXCR-4 expression in the population of CD34+/HLA-DR^bright and CD34+/CD38^bright cells. Based on the assessment of ten LP products, we found that the mean proportion of CD34+ cells coexpressing CD4 and CXCR-4 was 6.2±2.3% [±SEM], suggesting that a small population of CD34+ cells are, in principle, susceptible for an infection with T-cell-tropic HIV-1 strains. In conclusion, our data suggest that CXCR-4 is present on the surface of hematopoietic progenitor cells – particularly more primitive CD34+ cells. CXCR-4 could play a role in the homing of CD34+ cells to stromal elements of the bone marrow via its natural ligand stromal-derived factor-1 (SDF-1). Received: April 21, 1998 / Accepted: August 10, 1998     

对氧磷酶1基因Gln192Arg多态性与阿尔茨海默病的相关性分析

目的 探讨中国汉族人群中对氧磷酶1（PON1）基因Gln192Arg单核苷酸多态性（SNP）与阿尔茨海默病（AD）的相互关系。方法采用实时定量PCR技术检测521例AD患者和578例健康老年人PON1基因Gln192Arg位点SN-P的分布,并通过OR做疾病关联分析。结果AD组（Q／R＋R／R）基因型频率较对照组低,统计分析差异有统计学意义（X^2=4．68,P=0．03）;等位基因频率差异也存在统计学意义,AD组R等位基因频率明显低于对照组（X^2=3．85,P=o．05）。logistic回归分析表明,调整年龄和性别的影响后,（Q／R＋R／R）基因型患AD的危险性是Q／Q基因型的0．71倍（P=0．044,95％CI=0．51～0．99）。结论中国汉族人群中PON1基因Gln192Arg位点R等位基因可能是AD的保护因素。     

A Gly15Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease

BACKGROUND: Genetic susceptibility, probably involving cytokines and their receptors, plays an important role in inflammatory bowel disease (IBD). In this study we examine the potential role of the interleukin-10 (IL-10) gene as a susceptibility gene in IBD. METHODS: We studied 17 sib-pairs with either Crohn disease (CD) or ulcerative colitis. After microsatellite analysis for allele-sharing, the IL-10 gene of sib-pairs who shared alleles was screened for nucleotide alterations in and around exons and the promoter region. The IL-10 promoter polymorphism at position -1082 was also determined. Function was evaluated by measuring IL-10 secretion by peripheral blood mononuclear cells stimulated with lipopolysaccharide or phorbol ester. The activity of recombinant immature wild-type and mutated IL-10 was tested in a proliferation assay with a human monocytic leukaemia cell line (HL60 cells). RESULTS: DNA sequencing revealed a G --> A point mutation in exon 1 at base position 43 in one sib-pair, both affected with CD. It was also found in 2 of their healthy siblings, but not in 75 unrelated healthy controls. This mutation results in a glycine to arginine substitution at amino acid position 15 of the leader sequence (Gly15Arg). The in vitro IL-10 secretion by mononuclear cells of the IL-10 Gly15Arg carriers was about 50% of healthy controls, matched for the -1082 polymorphism in the IL-10 promoter region. Incubation of HL60 cells with recombinant mutated IL-10 showed a markedly reduced cell proliferation compared to wild-type IL-10. CONCLUSION: A Gly15Arg mutation in the leader sequence of IL-10 was found in a multiple CD-affected family. This altered leader sequence decreases IL-10 secretion, thereby reducing the anti-inflammatory effect.     

Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene

Mutations causing hypertrophic cardiomyopathy have been described in nine genes encoding sarcomeric proteins. We report a new mutation in three families, with a C-->G transversion in nucleotide 12 307 of the beta-myosin heavy chain gene, located at the essential light chain interacting region, resulting in the replacement of arginine by glycine at amino acid residue 723. PCR amplification of the selected regions followed by single strand conformation polymorphism analysis, DNA sequencing of the polymorphic patterns and restriction analysis were used to detect the mutation. A total of 23 individuals were diagnosed as carriers, and seven were obligate carriers or had been clinically diagnosed. The Arg723Gly mutation was associated with a malignant phenotype. Ten out of 30 affected members died suddenly or needed an implantable cardioverter-defibrillator at a mean age of 42, and seven members developed progressive heart failure, leading to death or heart transplant in five, at a mean age of 50 years. Echocardiography showed non-obstructive left ventricular hypertrophy in affected members older than 20 (sensitivity 68%). Mean survival of affected members was 51 years. In conclusion, a new mutation Arg723Gly in beta-myosin heavy chain gene is reported which shortens life expectancy because of sudden death and end-stage heart failure.     

湖南籍汉族强直性脊柱炎患者IL-1RN IL-1β基因多态性分析

目的研究白细胞介素(IL)-1RN、IL-1β基因多态性与强直性脊柱炎(AS)的相关性。方法自100例AS患者及92名健康对照者外周血中提取DNA,采用PCR-SSP方法检测IL-IRN基因第二内含子VNTR复等位基因及IL-1β基因 3953单核苷酸多态性。结果AS患者中IL-IRN*2等位基因频率显著高于健康对照者。结论AS与IL-1RN*2等位基因相关联。     

Association between obesity and a polymorphism in the beta(1)-adrenoceptor gene (Gly389Arg ADRB1) in Caucasian women

INTRODUCTION: Genetic variants affecting adrenoceptors have been suggested to influence body fatness. A putative gain-of-function polymorphism in the beta(1)-adrenoceptor was recently discovered (Gly389Arg ADRB1). We examined the association between Gly389Arg ADRB1 and obesity status in a large cohort of well-characterized individuals. METHODS: First, a large cohort of 931 Caucasian women (55.0+/-12.2 y) were genotyped for Gly389Arg ADRBbeta1 and we examined the association of the Arg allele with body weight and BMI (Gly/Gly, n=54; Gly/Arg, n=360; Arg/Arg, n=517). To further examine phenotypes regulating energy balance and body fatness, we examined the contribution of the Arg allele to body composition (DEXA), fat distribution (CT scan), resting energy expenditure, energy and macronutrient intake, maximal oxygen capacity, and physical activity in a subsample of 214 women from the main cohort that had been carefully characterized (Gly/Gly, n=19; Gly/Arg, n=82; Arg/Arg, n=113). RESULTS: In the entire cohort (n=931), allele frequencies were 0.25 and 0.75 for the Gly and Arg alleles, respectively. In this cohort, we found that each Arg allele was associated with greater body weight of 2.91 kg (P=0.01) and BMI of 0.86 kg/m(2) (P=0.05). Accordingly, in the subsample of women, each Arg allele was associated with greater fat mass (3.71 kg; P=0.008). Other phenotypes were not significantly associated with the presence of the Arg allele. CONCLUSIONS: This is the first study to investigate the relationship between the Gly389Arg ADRB1 variant and obesity. We found that the Arg allele is associated with greater body weight and BMI in Caucasian women due to a greater fat mass.     

A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis

Background

Stomatocytoses are a group of inherited autosomal dominant hemolytic anemias and include overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis, hereditary cryohydrocytosis and familial pseudohyperkalemia.

Design and Methods

We report a novel variant of hereditary stomatocytosis due to a de novo band 3 mutation (p. G796R-band3 CEINGE) associated with a dyserythropoietic phenotype. Band 3 genomic analysis, measurement at of hematologic parameters and red cell indices and morphological analysis of bone marrow were carried out. We then evaluated the red cell membrane permeability and ion transport systems by functional studies of the patient’s erythrocytes and Xenopus oocytes transfected with mutated band 3. We analyzed the red cell membrane tyrosine phosphorylation profile and the membrane association of the tyrosine kinases Syk and Lyn from the Src-family-kinase group, since the activity of the membrane cation transport pathways is related to cyclic phosphorylation-dephosphorylation events.

Results

The patient showed mild hemolytic anemia with circulating stomatocytes together with signs of dyserythropoiesis. Her red cells displayed increased Na⁺ content with decreased K⁺content and abnormal membrane cation transport activities. Functional characterization of band 3 CEINGE in Xenopus oocytes showed that the mutated band 3 is converted from being an anion exchanger (Cl⁻, HCO₃⁻) to being a cation pathway for Na⁺ and K⁺. Increased tyrosine phosphorylation of some red cell membrane proteins was observed in diseased erythrocytes. Syk and Lyn membrane association was increased in the patient’s red cells compared to in normal controls, indicating perturbation of phospho-signaling pathways involved in cell volume regulation events.

Conclusions

Band 3 CEINGE alters function from that of anion exchange to cation transport, affects the membrane tyrosine phosphorylation profile, in particular of band 3 and stomatin, and its presence during red cell development likely contributes to dyserythropiesis.     

A polymorphism within the interleukin 1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis.

OBJECTIVE: Genetic factors that predispose individuals to ankylosing spondylitis (AS) are not fully understood, but are unlikely to be restricted to HLA-B27. Proinflammatory cytokines are implicated in the development of sacroiliitis. We have examined the allele frequencies of three polymorphic sites in the interleukin (IL)-1 genes in AS patients to investigate whether genetic regulation of IL-1 production could be implicated in AS pathogenesis. METHODS: DNA from 188 AS patients, 115 healthy controls and 81 HLA-B27-positive healthy controls, all from the West of Scotland, were examined with the polymerase chain reaction in a case-controlled study. Polymorphic sites in genes of the IL-1 family were examined, including the 86-base pair variable number tandem repeat within intron 2 of the IL-1Ra gene, and the restriction fragment length polymorphisms at positions -889 in the IL-1alpha gene and -511 in the IL-1beta gene. RESULTS: No significant differences were seen at the polymorphic alleles in the IL-1alpha and IL-1beta genes, but there was a significant increase in the carriage of allele 2 in the IL-1Ra in the AS patients compared with local controls (16 vs 8%, odds ratio 2.3, 95% confidence interval 1.2-4.4, P=0.01). CONCLUSION: This report of an association with a polymorphic site within the IL-1 locus and AS suggests that genes other than B27 may well be involved in the pathogenesis of AS.     

胰岛素受体底物1（IRS-1）基因Gly972Arg突变与中国人糖尿病的相关性

目的 研究胰岛素受体物１（ＩＲＳ－１）基因Ｇｌｙ９７２Ａｒｇ突变与中国人糖尿病的相关性。方法 随机选取上海地区中国人３５９例,用ＰＣＲ／ＢｓｔＮ１酶解法检测Ｇｌｙ９７２Ａｒｇ突变。结果 本组中国人中仅发现２例该突变且均为非糖尿病者。结论 该突变可能不是中国人糖尿病的重要遗传因素。