Clinical characteristics of anti-glucose-6-phosphate isomerase antibody-positive Japanese patients with rheumatoid arthritis

Abstract

Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are known to be arthritogenic in mice. These Abs are elevated in several forms of arthritic condition in humans, although their prevalence in rheumatoid arthritis (RA) patients is still in debate. Some RA patients have increased levels of anti-GPI Abs, but their clinical manifestation and relevance to other Abs are not clearly elucidated. The aims of this study were to explore the clinical and hematological characteristics of RA with anti-GPI Abs, and to compare their prevalence in RA patients, systemic lupus erythematosus (SLE) patients, and healthy subjects (HS) in a Japanese population. Anti-GPI Abs were positive in 16 patients with RA (12%, n = 137), in 10 patients with SLE (8%, n = 131), and in 6 HS (4%, n = 139). C-reactive protein (CRP), immunoglobulin G, and the antinuclear antibody titer were higher in anti-GPI-positive patients than in those who were negative (P = 0.049, P = 0.0003, and P = 0.002, respectively). Moreover, the positivity of anti-GPI Abs was correlated with CRP more than with rheumatoid factor in RA patients. It is unclear whether anti-GPI Abs can predict the progress of disease, but the prevalence of these Abs was higher in active RA patients with severe arthritis, suggesting that anti-GPI Abs may be related to the pathogenesis of severe forms of arthritis.     

老年起病的类风湿关节炎血清中葡萄糖6磷酸异构酶的临床意义

目的探讨葡萄糖6磷酸异构酶（GPI）在老年起病的类风湿关节炎（EORA）患者血清中的临床意义,探讨其与EORA病情活动性之间的相关性。方法对36例EORA患者及48例健康老年人的血清进行了GPI的测定,并在EORA患者中对GPI与病情活动性之间的关系进行了分析。结果 36例EORA患者中,GPI阳性率为75%（27/36）。48例健康老年人中,仅有5例检测到GPI,GPI阳性率为10.4%（5/48）。GPI在EORA患者中的敏感性及特异性分别为75%及82.7%。以28处关节疾病活动度积分（DAS28）来评价EORA患者的病情活动性,在EORA患者中,GPI阳性组患者的病情活动性显著高于GPI阴性组患者（P〈0.05）。结论 GPI有助于EORA的诊断及病情活动性判断。     

葡萄糖-6-磷酸异构酶mRNA在RA患者外周血单个核细胞中的表达及意义

目的探讨葡萄糖-6-磷酸异构酶（glucose-6-phosphate isomerase，GPI）mRNA在类风湿关节炎（RA）患者外周血单个核细胞（PBMCs）中的表达及其与RA疾病活动性的关系。方法对30例RA活动期患者、30例RA缓解期患者、30例其他风湿性疾病患者及30名健康体检者，采用反转录聚合酶链反应（RT—PCR）半定量检测PBMCs中GPImRNA的表达水平。结果RA活动期患者GPImRNA的表达水平明显高于RA缓解期患者、其他风湿性疾病患者及正常对照组（P〈0．05），在RA活动组和RA缓解组，差异亦有统计学意义（P〈0．05）。结论GPImRNA在部分RA患者中高表达，其可能在RA发病机制中起作用，并与疾病的活动性相关。     

葡萄糖-6-磷酸异构酶抗原对类风湿关节炎诊断的意义

目的 研究葡萄糖-6-磷酸异构酶(G6PI)抗原在类风湿关节炎(RA)中的诊断意义.方法 用酶联免疫吸附试验(ELISA)双抗体夹心法检测106例RA患者,53例其他风湿性疾病和35名健康志愿者血清中的G6PI抗原的分布.还同时检测了类风湿因子(IgM-RF)、抗环瓜氨酸肽(CCP)抗体、抗角蛋白抗体(AKA)、C反应蛋白(CRP)、红细胞沉降率(ESR).并对98例RA患者行手足x线片,将其按修正的Sharp评分,分为有骨侵蚀组与无骨侵蚀组.结果 ①RA患者血清中G6PI浓度显著高于其他风湿病组和健康对照组(P<0.05).检测G6PI对RA的诊断价值,采用受试者工作曲线(ROC),诊断RA的最佳临界值为0.225μg/ml,此时的灵敏性为0.868,特异性为0.853.②G6PI与IgM-RF之间具有相关性(rs=0.504,P<0.05),G6PI与抗CCP抗体之间未显示出相关性(rs=0.078,P=0.503).③通过Spearman相关性分析.未发现G6PI抗原与病情活动性指标如ESR、CRP等有相关性.④经单因素分析G6PI抗原与骨侵蚀无关(P<0.05),IgM-RF与骨侵蚀具有相关性(P<0.05).结论 G6PI抗原在部分RA患者血清中显著升高,抗G6PI抗原对RA具有良好的敏感性(86.8%)和特异性(85.3%),能作为RA患者的一种新的标志物.G6PI抗原与IgM-RF有相关性,但不完全重叠.此研究未发现G6PI与病情活动性指标及关节侵蚀之间有关联.     

Treatment adherence in patients with rheumatoid arthritis and systemic lupus erythematosus

This study assessed self-reported adherence in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) from underserved healthcare settings. We conducted a cross-sectional survey of 102 ethnically diverse patients--70 with RA and 32 with SLE--attending rheumatology clinics at publicly funded hospitals in Houston, Texas; 43% were Hispanic, 32% African-American, and 25% White. Treatment adherence was evaluated using the compliance questionnaire rheumatology (CQR; 0, low adherence and 100, high adherence) and the questionnaire of the Adult AIDS Clinical Trials Group (AACTG). The patients were also asked how often they forgot to take their prescribed medications or discontinued them on their own. Mean patient age was 48.5 years; 75% were female, 32% were African-American, 43% Hispanic, and 25% White. Only one third reported never forgetting to take their medications; 40% reported having stopped their medications on their own because of side effects, and 20% because of lack of efficacy. Mean CQR score was 69.1 +/- 10.5, suggesting moderate adherence overall. Differences were also observed across ethnic groups: 23% of ethnic minority patients had problems taking their medications at specified times compared to 11% of Whites (p = 0.03). Lower education and side effects were associated with lower adherence. No differences were observed between RA and SLE patients. Many patients with RA and SLE report problems with treatment adherence. These appear to be more prevalent in African Americans and Hispanics than Whites; the impact of decreased adherence on outcomes could be significant and should be considered when treating patients with RA and SLE.     

类风湿关节炎活动期滑液中葡萄糖6-磷酸异构酶水平及与抗环瓜氨酸肽抗体的关系

目的 检测葡萄糖-6-磷酸异构酶(GPI)在类风湿关节炎(RA)活动期膝关节滑液中的含量,并探讨滑液中GPI与抗环瓜氨酸肽(CCP)抗体的关系.方法 用酶联免疫吸附法(ELISA)检测22例RA活动期患者和37例骨关节炎活动期患者滑液中GPI和抗CCP抗体的浓度.组间比较采用t检验,相关性分析采用Spearman相关分析.结果 RA活动期患者膝关节滑液中的GPI浓度高于骨关节炎活动期患者[(9.6±8.4)和(0.9±1.8)μg/ml],差异有统计学意义(P＜0.01);RA活动期患者与骨关节炎活动期患者滑液的抗CCP抗体浓度分别为(14.61±18.64)和(1.42:±0.09) U/ml,差异有统计学意义(P＜0.01);RA活动期患者膝关节滑液中GPI含量和抗CCP抗体浓度呈正相关(r=0.447,P=0.037).结论 GPI在RA活动期患者滑液中高表达,可能与RA发生发展过程中慢性滑膜炎、骨质破坏有关.GPI与抗CCP抗体呈正相关,两者可作为RA实验室诊断的参考指标.     

Atypical mycobacteriosis in two patients with rheumatoid arthritis

We report two cases of rheumatoid arthritis (RA) with atypical mycobacteriosis. Opportunistic infections are critical complications for rheumatic diseases. The use of steroids or immunosuppressants may increase the risk of opportunistic infections. However, these reports are rare in that they demonstrate atypical mycobacterial infections as complications of RA, even though no immunosuppressive agents were used. We discuss the characteristics of atypical mycobacterial infections of the lung in RA. Received: January 22, 2001 / Accepted: July 21, 2001     

Pharmacokinetics and efficacy of low-dose methotrexate in patients with rheumatoid arthritis

This article evaluates the relationship between the pharmacokinetics of methotrexate (MTX), its efficacy in the treatment of rheumatoid arthritis (RA), and serum folic acid (FA) levels. The pharmacokinetics of MTX was studied in 29 patients with RA treated with low-dose MTX. The weekly dose of MTX was given orally at 2–4mg every 12h over a period of 24–36h. Blood samples were taken 4h after the first administration in any given week. A Bayesian method was used to estimate individual MTX pharmacokinetic variables. We then investigated the efficacy of MTX and the serum FA levels in these patients. We examined C-reactive protein levels (CRP) and the erythrocyte sedimentation rate (ESR), and analyzed the values obtained before and after MTX treatment in order to evaluate the efficacy of the MTX treatment. The degree of improvement in CRP and ESR was significantly correlated with the length of time the MTX concentration–time curve remained above 0.02µM in one week. Furthermore, the degree of improvement in CRP was also significantly correlated with the area under the concentration–time curve (AUC) for MTX. These results suggest that serum MTX measurements could be useful in determining individual patient regimens.     

血清葡萄糖-6-磷酸异构酶在类风湿性关节炎中的应用

目的：探讨血清中葡萄糖-6磷酸异构酶（G6PI）对类风湿性关节炎（RA）诊断及与其他自身免疫性疾病鉴别诊断中的价值。方法：采用酶联免疫吸附试验（ELISA）检测137例RA患者、141例其他风湿病患者和60例健康对照血清中GPI抗原的浓度,RA患者还检测了抗环胍氨酸肽抗体（抗CCP抗体）及类风湿因子（RF）的浓度。结果：137例RA患者血清中GPI浓度为（3．01±1．33）mg／L,141例其他风湿性疾病组为（0．27±0．16）mg／L,60例健康对照组为（0．07±0．03）mg／L。RA患者血清中GPI浓度显著高于其他风湿病组和健康对照组（P〈0．01）;在RA活动组和RA非活动组中亦差异有统计学意义（P〈0．01）。GPI抗原对RA诊断的敏感性为62．8％,特异性为95．7％。3个指标联合检测的特异性达100％。结论：GPI在部分RA患者血清中显著升高,有可能成为诊断RA及判断其疾病活动性的一个新指标。     

The frequency of circulating immune complexes in rheumatoid arthritis and systemic lupus erythematosus

Summary Sera from patients with rheumatoid arthritis and systemic lupus erythematosus have been examined for the presence of complement-fixing immune complexes using three assays, (a) a fluid phase Clq binding assay, (b) a solid phase Clq binding assay and (c) the Raji cell assay.By simultaneously screening all the sera within each disease group we established that circulating immune complexes frequently occur but that there is a discordance between the assays, even between the two assays involving binding to Clq. Distinct clinical profiles emerged with the fluid phase Clq binding assay being most frequently positive in sera from patients with extra-articular rheumatoid arthritis. The solid phase Clq binding assay and the Raji cell assay were more frequently positive in sera from patients with systemic lupus erythematosus. The prevalence of circulating immune complexes and the comparative performance of the three assays in each disease is examined in detail.     

Treatment of infected total knee arthroplasty in patients with rheumatoid arthritis

Abstract

The primary aim of treating infected knee joints after total knee arthroplasty is to eradicate the infection, but this is difficult to achieve. We reviewed the treatment of infections that occurred after total knee arthroplasty in patients with rheumatoid arthritis. The subjects were 14 patients with rheumatoid arthritis (3 men, 11 women; ages 38–81 years) who had 14 infected knee joints. The outcome was preservation of the implant in two cases, revision arthroplasty in six cases, arthrodesis in three cases, resection arthroplasty in one case, amputation in one case, and death in one case. If there is no loosening, preservation of the implant should be attempted. If preservation is impossible, revision arthroplasty is the next best option considering the effect on daily activities in patients with the disease affecting multiple joints.     

血清中6-磷酸葡萄糖异构酶抗原升高在类风湿关节炎中的意义探讨

目的评估葡萄糖-6-磷酸异构酶(glucose-6-phosphate isom erase,GPI)在类风湿关节炎(rheum atoid arthritis,R A)发病中的意义。方法用酶联免疫吸附试验(ELISA)双抗体夹心法检测100例R A病人、98例其他风湿性疾病病人和108名健康体检者的血清中的G PI浓度,RA病人还检测了抗环瓜氨酸肽(CCP)抗体、类风湿因子(rheum atoid factor,RF)和C反应蛋白(CRP)的浓度。结果RA病人中G PI的浓度为(2.4±5.0)滋g/m l,正常对照组为(0.12±0.14)滋g/m l(P<0.01),其他风湿病组为(0.12±0.08)滋g/m l(P<0.01),GPI的浓度在RA活动组和非活动组差异有统计学意义(P<0.01);R A组23%的病人浓度高于2滋g/m l。经过Logistic回归分析发现GPI的浓度与RA病人的关节肿、疼痛成正相关。结论GPI在部分R A病人,尤其在活动期的RA病人血清中异常升高,可以作为RA临床诊断和评估的实验室指标。     

Analysis of the affected joints in rheumatoid arthritis patients in a large Japanese cohort

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disorder involving multiple joints. We investigated the distribution of the affected joints and the relationships among this distribution, the disease activity, and the disease duration in Japanese RA patients by cross-sectional analysis using the National Database of Rheumatic Diseases by iR-net in Japan.

Materials and methods

A total of 6408 RA patients registered in the database were analyzed. In each patient, the location of joint swelling and joint tenderness of 68 joints was examined, and the relationships among the distribution of the affected joints, the disease activity as determined using the DAS28-ESR, and the disease duration were analyzed statistically.

Results

For the 6408 RA patients examined, the wrist was the most frequently affected site. There were some differences in the prevalence of tenderness and swelling; tenderness was frequently observed in large joints such as the knee, elbow and shoulder, while swelling was frequently observed in small joints such as the metacarpophalangeal joints. Although the frequency of involvement increased in all joints as disease activity increased, the pattern of distribution was not affected by disease activity. Furthermore, the distribution was not influenced by disease duration.

Conclusions

Based on the results of this study, we can draw the following conclusions: (1) the wrist was the most affected joint; (2) there was a discrepancy between the distribution of swollen joints and that of tender joints; and (3) the distribution of affected joints was uniform regardless of disease activity.     

Treatment of infected total knee arthroplasty in patients with rheumatoid arthritis

The primary aim of treating infected knee joints after total knee arthroplasty is to eradicate the infection, but this is difficult to achieve. We reviewed the treatment of infections that occurred after total knee arthroplasty in patients with rheumatoid arthritis. The subjects were 14 patients with rheumatoid arthritis (3 men, 11 women; ages 38–81 years) who had 14 infected knee joints. The outcome was preservation of the implant in two cases, revision arthroplasty in six cases, arthrodesis in three cases, resection arthroplasty in one case, amputation in one case, and death in one case. If there is no loosening, preservation of the implant should be attempted. If preservation is impossible, revision arthroplasty is the next best option considering the effect on daily activities in patients with the disease affecting multiple joints.     

Hemagglutination of preoperative blood donation in patients with rheumatoid arthritis

Abstract

We gave preoperative blood transfusions to 37 patients with rheumatoid arthritis (RA) and 35 patients with osteoarthritis (OA), including some whose baseline hemoglobin level was less than 10?g/dl. Transfusion packs can preserve whole blood containing citrate phosphate dextrose (CPD) for 3 weeks. The baseline hemoglobin level of RA cases was 10.4?g/dl (range 8.4–13.1?g/dl), and that of OA cases was 11.9?g/dl (range 10.4–15.0?g/dl). By collecting 200–400?g every week before the operation, the total was 800–1200?g. Erythropoietin was given to patients intramuscularly when their hemoglobin was less than 13?g/dl after blood had been collected. Hemagglutination, with diameters of more than 1?cm, made filter occlusions in 11 RA cases (30%) and one OA case (3%) (P < 0.0031) after retransfusion. There were no differences between hemagglutination patients (agglutination group) and nonhemagglutination patients (nonagglutination group) regarding baseline C-reactive protein (CRP), white blood cells, platelets, or fibrinogen. We could not predict the formation of macrohemagglutination in the packs collected during the clinical course. In RA cases, allogenic transfusions were performed for four cases (36%) in the agglutination group and for one case (12%) in the nonagglutination group. Preoperative transfusion for the RA patients showed hemagglutination in some cases, and highlighted the need for modifications to reduce these hemagglutinations.     

Hemagglutination of preoperative blood donation in patients with rheumatoid arthritis

We gave preoperative blood transfusions to 37 patients with rheumatoid arthritis (RA) and 35 patients with osteoarthritis (OA), including some whose baseline hemoglobin level was less than 10g/dl. Transfusion packs can preserve whole blood containing citrate phosphate dextrose (CPD) for 3 weeks. The baseline hemoglobin level of RA cases was 10.4g/dl (range 8.4–13.1g/dl), and that of OA cases was 11.9g/dl (range 10.4–15.0g/dl). By collecting 200–400g every week before the operation, the total was 800–1200g. Erythropoietin was given to patients intramuscularly when their hemoglobin was less than 13g/dl after blood had been collected. Hemagglutination, with diameters of more than 1cm, made filter occlusions in 11 RA cases (30%) and one OA case (3%) (P 0.0031) after retransfusion. There were no differences between hemagglutination patients (agglutination group) and nonhemagglutination patients (nonagglutination group) regarding baseline C-reactive protein (CRP), white blood cells, platelets, or fibrinogen. We could not predict the formation of macrohemagglutination in the packs collected during the clinical course. In RA cases, allogenic transfusions were performed for four cases (36%) in the agglutination group and for one case (12%) in the nonagglutination group. Preoperative transfusion for the RA patients showed hemagglutination in some cases, and highlighted the need for modifications to reduce these hemagglutinations.     

Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis patients

Objectives

Rheological characteristics of blood are strongly linked to atherothrombosis in the general population, but its contribution to atherosclerosis in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is currently unclear. This work examines the relationship between blood rheology, traditional cardiovascular (CV) risk factors, inflammation and subclinical atherosclerosis in SLE and RA.

Methods

Whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte deformability (ED), aggregation (EA) and erythrocyte NO production were measured in 197 patients (96 SLE and 101 RA) and compared to 97 controls, all females without previous CV events. Clinical information was obtained and fasting lipids and acute phase reactants were measured. The relationship between hemorheological parameters, CV risk factors and inflammation was assessed in patients and the impact of these variables on carotid intima-media thickness (cIMT) was evaluated in univariate followed by multivariate regression analyses.

Results

WBV and ED are significantly lower in patients, while EA is elevated as compared with controls. Hemorheological disturbances correlate with CV risk factors and markers of inflammation and are more profound in patients with metabolic syndrome. Multivariable analysis showed that menopause (OR 34.72, 95%CI 4.44–271.77), obesity (OR 4.09, 95%CI 1.00–16.68) and WBV (OR 3.98; 95%CI 1.23–12.83) are positively associated whereas current corticosteroid dose (OR 0.87; 95%CI 0.78–0.98), and erythrocyte NO production (OR 0.16; 95%CI 0.05–0.52) are negatively associated with cIMT.

Conclusion

Disturbed hemorheological parameters in SLE and RA women are related to the presence of CV risk factors and inflammation. WBV and erythrocyte NO are independently associated with the early stages of atherosclerosis.     

Severe erosive arthropathy requiring surgical treatments in systemic lupus erythematosus

We report a case of 43-year-old woman with an overlap syndrome of systemic lupus erythematosus (SLE) and dermatomyositis who developed erosive arthritis with extracapsular cysts involving multiple joints. An extensive synovectomy for the left wrist joint and a total joint replacement for the right hip joint were required to achieve complete symptom relief. She was not diagnosed with rheumatoid arthritis (RA). This was a rare case of SLE manifesting non-RA erosive arthritis that required surgical interventions.     

Severe erosive arthropathy requiring surgical treatments in systemic lupus erythematosus

Abstract

We report a case of 43-year-old woman with an overlap syndrome of systemic lupus erythematosus (SLE) and dermatomyositis who developed erosive arthritis with extracapsular cysts involving multiple joints. An extensive synovectomy for the left wrist joint and a total joint replacement for the right hip joint were required to achieve complete symptom relief. She was not diagnosed with rheumatoid arthritis (RA). This was a rare case of SLE manifesting non-RA erosive arthritis that required surgical interventions.