类风湿关节炎HLA-DQβ1易感基因研究

目的 探讨HLA-DQβl基因多态性在中国汉族类风湿关节炎(RA)发病中的作用及与患者临床指标的关系。方法 选取类风湿关节炎患者及健康对照各42例，以序列特异性引物PCR(PCR—SP)技术对HLA-DQβl的42种亚型进行检测，并分析患者病情、免疫学指标及关节破坏程度与各亚型之间的关系。结果 在RA患者组中HLA-DQβl*0401和*0501等位基因的频率(分别为11．9％、7．1％)显著高于对照组(分别为3．6％、1．2％)(X^2＝4．085，RR＝4．06；X^2＝4．725，RR＝6．83;P＜0．05)，而HAL-DQβ1*0602的频率则明显低于对照组(7．1％vs19．0％)(x^2＝5．23 ;P＜0．05)。HLA-DQβ*l0401／0301或*0401/0303及HLA-DQβl*0501/0301基因型在RA患者中的阳性率(分别为19．05％、9．52％)显著高于对照组(分别为2．38％、0％＞(X^2＝6．098，P＝0．014；X^2＝4．200，P＝0．040)，差异具有显著性。HLA-DQβl*03阳性的RA患者与阴性患者相比发病年龄早，关节破坏严重，关节外表现明显增多，并与部分实验室指标异常呈正相关，其中HLA-DQβ1*03纯合子(HLA-DQβl*03/03)患者的上述异常更为显著。结论 HLA-DQβl*0401及*0501亚型、HLA-DQβl*0401／03及HLA-DQβ1l*0501用301基因型可能与中国汉族RA的易感性有关，而HLA-DQβl*0602可能为抗RA基因;HLA-DQβl*03则与RA的严重程度相关。     

HLA—DR4基因检测在类风湿关节炎诊治中的意义探讨

为了研究ＨＬＡ－ＤＲ４基因检测在类风湿关节为诊治中的意义，对５０例类风湿关节炎患者进行了ＨＬＡ－ＤＲ４的（ＰＣＲ－ＳＳＰ方法）检测，同时结合患者的临床表现和实验室指标进行分析。结果显示：ＨＬＡ－ＤＲ４阳性者３１例（阳性率为６２％）；比较ＨＬＡ－ＤＲ４阳性和阴性两组患者其他指数，可见，ＩＨＬＡ－ＤＲ４阳性组的关节疼痛指数、ＥＳＲ、类风湿因子（ＲＦ）滴度均明显高于ＨＬＡ－ＤＲ４阴性组（Ｐ值分别〈０．０     

HLA—DR基因与类风湿关节炎

ＨＬＡ－ＤＲ基因与类风湿关节炎田新平蒋明类风湿关节炎（ＲＡ）是一种累及关节滑膜的常见风湿病，我国平均发病率为０．３％。但其病因及发病机制仍不清楚。近年来，随着分子生物学技术和免疫学的发展，对ＲＡ的免疫遗传学进行了深入的研究。一、ＨＬＡ－Ⅱ类基因及Ⅱ类...     

HLA-DR4基因与类风湿关节炎自身抗体的相关性研究

ＨＬＡＤＲ４基因与类风湿关节炎自身抗体的相关性研究田新平甘晓丹于孟学李永哲崔京涛周志杰类风湿关节炎（ＲＡ）是一种以关节滑膜炎症为主要表现的自身免疫性疾病，存在体液免疫和细胞免疫学异常。体液免疫异常的一个表现为血清中有多种自身抗体。ＲＡ的发病机制不清...     

类风湿关节炎中HLA-DR分子表达量的改变

目的 探讨外周血淋巴细胞表面HLA－DR分子表达量在类风湿关节炎（RA）发病中的作用。方法 选择RA患者活动期34例,静止期40例;正常对照（NC）43例,急性风湿性关节炎（ARA）21例及系统性红斑狼疮（SLE）28例,分别检测外周血淋巴细胞表面的HLA－DR分子表达量。同时在活动期RA治疗3个月前后,分别检测HLA－DR分子表达量、类风湿因子（RF）及对症状计分,进行统计学分析。结果 ①RA活动组HLA－DR分子表达水平最高（P＜0．05）,ARA组及RA静止组较NC组明显增高（P＜0．05）,而SLE组与NC组无明显差别（P＞0．05）;②RA活动组HLA－DR分子表达量及RF的阳性率均在治疗后显著下降,临床症状明显改善。结论 ①检测患者外周血淋巴细胞表面HLA－DR表达量有助于RA的诊断及监测RA活动度;②HLA－DR分子表达量与RF的动态变化相平行;③动态观察HLA－DR分子表达量变化有助于判断RA病情及其预后。     

HLA-DR4等位基因与类风湿关节炎疗效的关系

目的：探讨对类风湿关节炎（RA）联合使用改善病情抗风湿药（DMARDs）的疗效与易感HLA－DR4基因携带的关系。方法 测定RA患者HLA－DR4携带频率,并作病程、关节功能及红细胞沉降率（ESR）、C反应蛋白（CRP）、类风湿因子（RF）比较分析后,分别于阳性者及阴性者联用甲氨蝶呤（MTX）、柳氮磺吡啶（SASP）及氯奎（CQ）等DMARDs,并观察疗效。结果 HLA－DR4携带使患者ESR、CRP及RF值升高,使RA病情复杂化,给联合治疗带来困难,表现在控制症状及生化指标恢复正常值的时间上,HLA－DR4阳性组比HLA－DR4阴性组显著延迟;在RF值恢复正常方面,HLA－DR4阳性组比HLA－DR4阴性组病例显著减少,上述两方面与RA预后密切相关。在药物的副作用方面,两组差异无显著性。结论 HLA－DR4可作为判断RA治疗的重要预后指标。     

HLA—DR抗原β链的共同表位与类风湿关节炎相关性研究

目的 探讨人类白细胞抗原（ＨＬＡ）－ＤＲ基因编码的共同表位（ＳＥ）与武汉籍汉族类风湿关节炎（ＲＡ）的相关性。方法 采用聚合酶链反应－序列特异性引物技术（ＰＣＲ－ＳＳＰ）,对武汉籍汉族人群７８例ＲＡ患者和１２６例健康者的ＨＬＡ－ＤＲＢ１＊０１、＊０４基因型进行检测。结果 ＲＡ患者中具有编码ＱＫＲＡＡ或ＱＲＲＡＡ的共同表位阳性率为４３．６％,明显高于正常对照组（１５．１％,ｐ〈０．０１）;ＳＥ阳怀的Ｒ     

贵州汉族类风湿关节炎患者HLA-DR4亚型多态性的研究

类风湿关节炎 (ｒｈｅｕｍａｔｏｉｄａｒｔｈｒｉｔｉｓ ,ＲＡ)的发病机制尚未彻底阐明。研究发现ＲＡ与ＨＬＡ ＤＲ4有不同程度的相关性 ,但ＤＲ4至少包括 2 2种亚型[1] ,不同亚型与ＲＡ的相关性不尽相同。为此我们采用序列特异性引物聚合酶链反应 (ＰＣＲ ＳＳＰ)技术 ,检测了贵州地区汉族ＲＡ患者ＤＲ4基因亚型的多态性 ,现报告如下。1　材料和方法1 1　研究对象本院风湿科 2 0 0 0— 2 0 0 1年住院ＲＡ患者 35例 ,诊断符合美国风湿协会 (ＡＣＲ) 1987年诊断标准[2 ] ,其中男性 7例 ,女性 2 8例 ,年龄 9～ 75岁 ,平均 4 6岁。 5 1份对照…     

汉族类风湿关节炎患者HLA—DR和—DQ基因分型研究

为探讨ＨＬＡ－ＤＲ和－ＤＱ等位基因与我国汉族类风湿关节炎（ＲＡ）的相关性，采用聚合酶链反应－限制性内切酶片段长度多态性分析（ＰＣＲ－ＲＦＬＰ）方法对汉族人群中３５例ＲＡ患者和１００名健康人的ＤＲ和ＤＱ位点进行ＤＮＡ定型分析。结果发现，ＤＲ４频率在正常人为２４．０％，在ＲＡ患者为５１．４％（Ｐ＜０．０１，ＲＲ＝３．３０）；ＤＲ４亚型位点分析发现２组均以ＤＲＢ１＊０４０５占多数，但ＤＲＢ１＊０４０５频率在ＲＡ组为３１．４％，高于正常人的１０．０％（Ｐ＜０．０１）。ＤＱ４频率在全部ＲＡ患者为３７．１％，在ＤＲ＋４ＲＡ患者为７２．２％，均高于全部正常人的１０．０％（Ｐ＜０．０１）和ＤＲ＋４正常人的４１．６％（Ｐ＝０．０３７６）；ＤＲ＋４－ＤＱ＋４ＲＡ患者的病情重于ＤＲ－４患者。结果提示，ＤＲ４、主要是ＤＲＢ１＊０４０５与ＲＡ相关，ＤＱ４可增加ＤＲ４对ＲＡ的易感性，ＤＲ＋４－ＤＱ＋４单倍型是ＲＡ病情严重程度的标志。     

Influence of long-term low-dose methotrexate therapy on periarticular and generalized osteoporosis in rheumatoid arthritis

Our objective was to evaluate the effect of low-dose methotrexate therapy on periarticular and generalized osteopenia in patients of rheumatoid arthritis (RA). Fifty-five women received one of four therapeutic regimens. The periarticular radial bone mineral density (BMD) was analyzed by dual energy X-ray absorptiometry. Generalized osteopenia was assessed by measuring the BMD and height of the lumbar spine (L₂-L₄). Vertebral deformity was also assessed on plain Xray film. Physical activity, age and menopausal status were similar among the four treatment groups. The decrease of lumbar BMD was greatest in the group given steroids plus another disease modifying antirheumatic drug (DMARD), followed by the steroid/methotrexate group, methotrexate group and the other DMARD group. The decreases of lumbar vertebral height was greatest in the steroid/methotrexate group, followed by the steroid/DMARD group, methotrexate group and the other DMARD group. Vertebral compression was found in 22% of the steroid/methotrexate group and 14% of the steroid/DMARD group. Radial periarticular BMD was significantly lower in patients with active wrist joint synovitis than in patients without synovitis, but was increased by methotrexate therapy. We conclude that low-dose methotrexate did not increase lumbar osteopenia or vertebral compression in RA patients and might preven periarticular osteopenia by suppressing synovitis     

Influence of long-term low-dose methotrexate therapy on periarticular and generalized osteoporosis in rheumatoid arthritis

Abstract

Our objective was to evaluate the effect of low-dose methotrexate therapy on periarticular and generalized osteopenia in patients of rheumatoid arthritis (RA). Fifty-five women received one of four therapeutic regimens. The periarticular radial bone mineral density (BMD) was analyzed by dual energy X-ray absorptiometry. Generalized osteopenia was assessed by measuring the BMD and height of the lumbar spine (L₂-L₄). Vertebral deformity was also assessed on plain Xray film. Physical activity, age and menopausal status were similar among the four treatment groups. The decrease of lumbar BMD was greatest in the group given steroids plus another disease modifying antirheumatic drug (DMARD), followed by the steroid/methotrexate group, methotrexate group and the other DMARD group. The decreases of lumbar vertebral height was greatest in the steroid/methotrexate group, followed by the steroid/DMARD group, methotrexate group and the other DMARD group. Vertebral compression was found in 22% of the steroid/methotrexate group and 14% of the steroid/DMARD group. Radial periarticular BMD was significantly lower in patients with active wrist joint synovitis than in patients without synovitis, but was increased by methotrexate therapy. We conclude that low-dose methotrexate did not increase lumbar osteopenia or vertebral compression in RA patients and might preven periarticular osteopenia by suppressing synovitis     

类风湿关节炎患者T细胞抗原受体BV基因的限制性取用初步研究

目的 研究类风湿关节炎（rheumatoid arthritis，RA）患者病灶部位即关节滑膜组织浸润的受某种自身抗原驱动的T淋巴细胞抗原受体（T cell receptor，TCP）β链的取用格局。方法 采用实时定量聚合酶链反应（polymerase chain reaction，PCR）的方法分析RA患者病灶部位T淋巴细胞抗原受体β链的取用：采用PCR—SSP方法对所调查的RA患者的人类自细胞抗原（human leucocyte antigen，HLA）进行了分型。结果 研究发现中国人群RA患者病灶关节滑膜浸润的T淋巴细胞抗原受体主要取用BV14和BV16家族：中国人群RA患者HLA基因型主要以HLA DRBI＊0405为主要特征，与白种人RA患者不同。结论 研究提示中国人群RA患者病灶区自身反应性T细胞具有TCR BV14和BV16的限制性取用．其中TCR BV16的偏移为国内外首次报道。而HLADRBI＊0405类风湿关节炎患者表现出TCR BV16取用的趋势，提示TCR BV16取用受主要组织相容性复合体（MHC）的约束，这为进一步分析诱发RA的发生的免疫异常和自身反应性T细胞的生物学特陛提供了重要试验基础。     

Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis

We evaluated lung function in a group of patients affected by juvenile rheumatoid arthritis (JRA), without clinical and/or radiological signs of respiratory involvement. We compared the effects on pulmonary function of methotrexate (MTX) therapy combined with non-steroid anti-inflammatory drugs (NSAIDs) to those of NSAIDs alone and correlated lung function to subtype onset, disease duration and disease activity. Our patients were 27 JRA children, subdivided into two groups according to the therapy (group A=14 patients, treated with a low dose of MTX and NSAIDs; group B=13 patients, treated with NSAIDs alone). Clinical evaluation, haematological data and pulmonary function tests (PFTs) were obtained in each group at baseline (time 0) and at 1 year (time 1). At time 0 and time 1 PFTs were altered in 51.8% of JRA patients. The restrictive pattern (reduced forced vital capacity, FVC) was the most frequent feature, observed in 22.2% of patients. In group A the mean values of FVC, FEV1 (forced expiratory flow in 1 s), FRC (functional residual capacity), TLC (total lung capacity) and DLCO (diffusing lung capacity of carbon monoxide) were significantly lower compared to those of group B, at time 0 and at time 1. No functional parameter was correlated to subtype, duration or activity of the disease. Our study confirms that abnormalities in PFTs may be detected in JRA patients, even in the absence of clinical and/or radiological signs of lung disease; MTX in combination with NSAIDs does not seem to affect lung function at 1 year more than NSAIDs alone. Received: 3 November 1997 / Accepted: 21 December 1997     

Methotrexate therapy in systemic-onset juvenile rheumatoid arthritis in Saudi Arabia: A retrospective analysis

Eighteen patients (nine girls, nine boys) with systemic onset juvenile rheumatoid arthritis (SO-JRA) treated with methotrexate (MTX) for a mean period of 18 months (range 6–41 months) were analysed to evaluate the safety and efficacy of MTX in this disease subtype. The MTX dose ranged from 2.5 to 15 mg/week with a mean cumulative dose of 684.9 mg/patient at the last follow-up visit. Systemic features were severe in 10 patients before MTX was started. None of these patients showed systemic features at the last follow-up visit. Sixteen patients (89%) showed improvement in both the active joint count (from a mean of 12.0 to 1.3 joints/patient) and function class (from a mean of 3.0 to 1.3) while receiving MTX. Eleven patients (61%) showed a significant decrease in the erythrocyte sedimentation rate (>50% of the initial value), an improvement in anaemia (haemoglobin >2 g) and reduced thrombocytosis (platelets 2×10⁵). Of the patients receiving corticosteroids, three patients (20%) were able to discontinue prednisone and the dose was reduced to less than 50% of the initial dose in seven patients (47%). At these doses of MTX, no gastrointestinal, hepatic or haematological toxicity was encountered and none of the patients withdrew because of toxicity or lack of efficacy. This report suggests that MTX is an effective and safe treatment in controlling systemic and articular features in this subtype of JRA.     

苦参碱对类风湿关节炎外周血淋巴细胞增殖抑制细胞周期影响的研究

目的 通过体外实验比较苦参碱(Mat)与甲氨蝶呤(MTX)对类风湿关节炎(RA)患者外周血淋巴细胞(PBL)生长、细胞周期的影响,探讨Mat对RA患者PBL的作用机制.方法 应用四甲基偶氮唑蓝(MTT)比色法测定不同时间、不同浓度干预的MTX及Mat吸光度(A)值,计算细胞抑制率;流式细胞术(FCM)检测48 h MTX及Mat的细胞周期.结果 ①MTX、Mat可抑制体外培养的PBL细胞生长,随着药物浓度的增大,A值下降,细胞抑制率(IR%)增加,呈剂量依赖性.48 h作用点IR%明显＞24 h作用点(P＜0.01).两药物比较差异无统计学意义(P＞0.05).②MTX、Mat可使细胞周期构成发生明显变化,与对照组相比差异有统计学意义(P＜0.01).G0/G1期细胞比例增高,S期和C2/M州期细胞比例降低.随着药物浓度增加,细胞增殖指数逐渐降低,呈剂量依赖性.两药物比较差异无统计学意义(P＞0.05).结论 Mat对体外培养的RA患者PBL生长的抑制作用及细胞周期的作用与MTX相当.推测Mat可能具有治疗RA的潜在价值.     

Listeria monocytogenes infection associated with methotrexate treatment for a patient with rheumatoid arthritis

Abstract

A 61-year-old women had been treated with methotrexate (MTX) since May 1993 for rheumatoid arthritis. She developed a high fever on 1 July 1997 and was diagnosed as having Listeria monocytogenes sepsis and meningoencephalitis. The encephalitis progressed inexorably and she died on 12 July. Although MTX is used as a first-line disease modifying anti-rheumatic drug, listeriosis should be remembered as a potentially fatal adverse effect.     

类风湿关节炎患者关节软骨细胞人类白细胞抗原-DR的表达

目的：观察人类白细胞抗原（HLA）-DR抗原在类风湿关节炎（RA）患者软骨细胞的表达情况,及其在软骨细胞诱导的自身T细胞增殖反应中的作用。方法：采用流式细胞仪和组织免疫荧光染色法检测HLA-DR抗原在7例RA患者软骨细胞和2例正常软骨细胞的表达,同时采用氚标记的胸腺嘧啶掺入法观察软骨细胞诱导的自身T细胞增殖反应。结果：流式细胞仪检测结果显示,HLA-DR表达阳性率在7例RA患者软骨细胞为（29±15）%,而在2例正常软骨细胞分别为3.7%和8.4%。组织免疫荧光染色结果显示,HLA-DR阳性软骨细胞主要位于软骨中上层。RA软骨细胞诱导自身T细胞增殖反应的刺激指数（SI）为5.8±2.9,高于2例正常软骨细胞的1.12和2.97。用抗HLA-DR单克隆抗体封闭软骨细胞表面的HLA-DR抗原后,SI下降为3.8±1.7。结论：RA软骨细胞有HLA-DR抗原的高表达,并能刺激自身T细胞增殖反应,提示RA软骨细胞具有抗原提呈功能。     

肽酰基精氨酸脱亚氨酶-4基因多态性与类风湿关节炎的相关性

目的 肽酰基精氨酸脱亚氨酶基因4-94位点(PADI4-94)和4-104位点(PADI4-104)基因的单核苷酸多态性(SNPs)与类风湿关节炎(RA)易感性的关系.方法 采用聚合酶链反应-连接酶检测反应(PCR-LDR)方法 鉴定116例RA患者和100名健康体检者基因及基因型,计算其频率,用X2检验统计分析.用酶联免疫吸附试验(ELISA)法检测RA外周血抗PADl4抗体及PADI4蛋白水平.结果①PADI4-94及PADI4-104位点存在A和G 2种等位基因,A/A,G/G和A/G 3种基因型,RA组/健康组PADI4-94等位基因A、G及其A/A、G/G和A/G基因型频率分别是0.460/0.392、0.540/0.608,0.204/0.186、0.283/0.402和0.513/0.412,2组差异无统计学意义(X2=1.996,P=0.157;X2=3.407,P=0.182);RA组/健康组PADI4-104等位基因A、G及其A/A、G/G和A/G基因型频率分别是0.412/0.345、0.588/0.655,0.150/0.144、0.32710.454和0.522/0.402,2组差异无统计学意义(X2=1.937,P=0.164;X2=3.780,P=0.151).③RA组PADI4-94/PADI4-104各基因型间红细胞沉降率(ESR),RA疾病活动关节评分28(DAS28)评分,C反应蛋白(CRP),抗环瓜氨酸肽(CCP)抗体,PADI4蛋白量及抗PADI4抗体水平差异无统计学意义(P值分别为0.46/0.67,0.62/0.57,0.12/0.23,0.81/0.43,0.78/0.75,0.38/0.31).结论 我国人群PADI4-94和PADI4-104两位点存在多态性,但其与RA的易感性无关.     

Association of the HLA-DR4 gene complex with auto-antibodies in rheumatoid arthritis patients

The HLA-DR4 gene complex plays a role in the pathogenesis of rheumatoid arthritis (RA). Auto-antibodies are a prominent serum feature of RA. In this study we explored the correlation of the HLA-DR4 gene complex with rheumatoid factor, anti-RA33/36 antibody, anti-keratin antibody (AKA) and anti-perinuclear factor (APF) in RA patients. Forty-five RA patients were involved in this study. The PCR-SSP method was used to examine the DR4 gene complex. Anti-RA33/36 antibody and RF were tested by Western blot and latex agglutination test respectively. AKA and APF were tested by the indirect immunofluorescence method. The DR4 gene complex is present in 60% of our patients. RF positivity was 68.9%. DR4(+) patients had a higher RF positive rate (66.7%) than DR4(−) patients (33.3%) (P<0.05). Anti-RA33/36 antibody was positive in 37.8% patients. It was present in 33.3% DR4(+) patients and in 38.9% DR4(−) patients. There was no significant difference. AKA (1∶80) was positive in 28.9% of our patients. It was present in 33.3% DR4(+) patients and in 22.2% DR4(−) patients. No significant difference could be found. APF could be detected in 53.3% of these patients. It was positive in 51.9% DR4(+) patients and 55.5% DR4(−) patients. There was no significant difference. In addition, no association could be found between RF, anti-RA33/36 antibody, AKA and APF. Therefore, although DR4 is an important indicator for severe RA and poor prognosis, it is only associated with RF. Moreover, no correlation could be found between these auto-antibodies.