Topics on immunological tests for rheumatoid arthritis

To prevent joint destruction, it is important to diagnose RA early and to speculate the prognosis. Several new laboratory tests have been developed for this purpose. In addition to rheumatoid factor (RF), IgG-RF, anti-agalactosyl IgG antibodies (CARF), and matrix metalloproteinase 3 (MMP-3) have become available as diagnostic tests for RA. Among them, anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) have the sensitivity and specificity of 81.0% and 92.4%, respectively, which are superior to other laboratory tests by ROC analysis. Moreover, the specificity of anti-CCP antibodies to diagnose early RA was much higher than that of RF, although the sensitivity of CARF was slightly high compared with that of RF. In contrast, MMP-3 is thought to be an evaluative test for the activity of RA because a significant correlation was found between MMP-3 and CRP, but MMP-3 has a possibility as a prognostic test to know the joint damage of RA. We have shown that the progression of joint damage (Sharp score) was faster in MMP-3-positive patients than negative patients. Anti-CCP antibodies was also reported to associate with the progression of joint damage and may be used also as a prognostic test. We next examined how efficiently was the diagnosis of RA made by combining these laboratory tests. Although anti-CCP antibodies are highly specific to RA, the specificity of RF was not so high but became up to 92% when combined with MMP-3. In order to diagnose RA efficiently, we may firstly examine RF, next MMP-3 if RF is positive, and anti-CCP antibodies if RF is negative.     

Multidisciplinary group therapy for rheumatoid arthritis

A group therapy approach to the psychosocial treatment of rheumatoid arthritis, with co-leaders from the disciplines of psychiatry, internal medicine, and physical medicine, is described. This group experience offers innovative treatment as well as a learning experience in psychosomatic medicine for the physicians involved. This type of group approach could become a valuable instrument for teaching psychiatry to residents and medical students.     

Immunosuppressive therapy in rheumatoid arthritis

Immunosuppressive drugs are used since 1951 for the treatment of rheumatoid arthritis. The most extensive used ones are azathioprine, cyclophosphamide, chlorambucil and methotrexate. The efficacy of these immunosuppressive drugs is clinical proven. Nevertheless it is necessary to use these drugs in severe disease only that has failed to respond to less toxic agents. The number of severe side effects is higher and the consequences of this therapy concerning cancerogenity is not clear yet. The efficacy and side effects of these drugs are discussed and guidelines for using immunosuppressive drugs in the treatment of rheumatoid arthritis are given.     

Tuberculous peritonitis during etanercept therapy for rheumatoid arthritis

In August 2010, a 73-year-old woman with rheumatoid arthritis receiving etanercept (ETN) therapy for two years, developed high-fever and abdominal fullness. Though she had not been exposed to tuberculosis, isoniazid prophylaxis was administrated. Antibiotics were not effective. CT images revealed the massive ascites and peritonitis, and Ga scintigraphy demonstrated notable uptake in the peritoneum. Ascites analysis showed an elevated adenosine deaminase activity value (104.9 IU/l) without malignant cells. Moreover, PCR and culture for Mycobacterium tuberculosis were positive. Finally, a diagnosis of tuberculous peritonitis was established. After initiating a standard anti-tuberculosis regimen with four drugs, her clinical condition ameliorated and ascites promptly regressed. Although the tuberculous peritonitis during ETN therapy is rare, this report emphasized the importance of initial suspicion of tuberculosis in these patients with tumor necrosis factor inhibitors such as ETN.     

Gene therapy for rheumatoid arthritis: recent advances

The treatment of rheumatoid arthritis (RA) in the last decade has made enormous advances with the use of biological therapies. However, these therapies have serious limitations such as the expense, side-effects, and the requirement for repeated injections, each of which can potentially be obviated by gene therapy. A gene therapy approach for the treatment of RA has the potential to stably deliver a gene product or multiple products in a target-specific, disease-inducible manner. There are many studies investigating gene therapy in RA, the majority of which have been designed to test proof-of-principle in an animal model. With an abundance of animal studies that have established much promise, the field is now at the early stage of moving towards human trials, where patient benefit needs to overshadow associated risks, especially since RA is publicly perceived as a non-life-threatening disease. Here, we provide an overview that focuses on advances in the application of gene therapy to RA over the last five years, including: novel targets and approaches; the viral and non-viral applications most likely to succeed in the clinic; advances in our understanding of the contralateral effect; the latest successes with anti-inflammatory cytokines; and a review of advancements towards clinical trials.     

State-of-the-art biological therapy of rheumatoid arthritis

State-of-the-art state of biological therapy of rheumatoid arthritis is analyzed. Its pathogenetic reasons are represented. Main direction of this therapy, such as blocking of tumor necrosis factor alpha and interleukin-1, inhibition of interaction between T-lymphocytes and antigen representing cells, elimination of B-cells, are considered. Special attention is devoted to new perspective methods of biological treatment, among which the special interest has first applied in RAMS Institute of Rheumatology method of interferon-gamma neutralization. Combination of anti-inflammatory, immune depressive and significant destructive actions leads to significant curative effect of biological therapy, exceeding results of the use of classic basic drugs including methotrexate. The achievement of clinical remission of rheumatoid arthritis first became the real aim of its treatment, and methods of biological therapy in contrast to former "disease-modifying" remedies could be considered as real "disease-controlling" drugs. Biological therapy revolutionized modern rheumatology and in the nearest years would demonstrated new fundamental accesses.     

类风湿关节炎单独甲氨蝶呤与三联疗法治疗的系统评价

背景：目前类风湿关节炎在治疗上选择甲氨蝶呤单独疗法还是三联疗法存在争议。目的：系统评价甲氨蝶呤单独疗法与甲氨喋呤+羟氯喹+柳氮磺吡啶三联疗法比较治疗类风湿关节炎的有效性和安全性。方法：计算机检索 Cochrane 图书馆、PubMed、EMBASE NRR (http://www.updatesoftware.com/National)、CCT(http://www.controlled-trails.com)和中国生物医学文献数据库(CBM)。手工检索(中文主要骨科杂志)。收集甲氨蝶呤单独疗法与甲氨喋呤+羟氯喹+柳氮磺吡啶三联疗法比较治疗类风湿关节炎的随机对照试验, 并评价纳入研究的方法学质量。统计采用Cochrane协作网提供的Revman 5.0软件进行分析。结果与结论：共纳入随机对照试验4篇,共297例患者,方法学质量均为B 级。Meta分析结果表明, 甲氨蝶呤单独疗法与三联疗法比较,甲氨蝶呤单独疗法在血沉方面的改善要大于三联疗法[MD=7.01 95%CI(2.82,11.19),P=0.001],三联疗法在关节改善情况方面优于单独疗法[OR=0.62 95%(0.41,0.95),P=0.03],在不良反应上,两者差异无显著性意义。而ACR因文献未提供详细数据未能做Meta分析。与三联疗法治疗相比,甲氨蝶呤单独疗法更明显降低成人类风湿关节炎的血沉,但在关节功能改善方面三联疗法要优于甲氨蝶呤单独疗法。而在不良反应上,两组差异无显著性意义。因这次系统评价纳入的病例数较少,尚需更多设计严格的大样本随机对照研究来增加证据的强度。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程全文链接：     

类风湿关节炎药物治疗基因多态性研究进展

类风湿关节炎(RA)是一种系统性疾病,可致关节破坏和残疾.治疗以传统DMARDs和生物制剂为主.药物疗效与患者基因多态性密切相关.药物主要包括甲氨蝶呤、来氟米特、柳氮磺胺吡啶和生物制剂如TNF拮抗剂、妥珠单抗、力妥昔单抗等.RA患者遗传背景是影响药物疗效的重要因素,必然对个体化治疗产生深远影响,因而研究基因多态性与RA患者疗效反应的相关机制具有重要意义.