B细胞清除疗法治疗类风湿关节炎

类风湿关节炎(RA)是一种以关节慢性炎症为主要表现的自身免疫性疾病,并且可以导致残疾。虽然RA的病因尚未明确,但最近15年关于RA发病机制的研究已经取得了较大的进展,其中最近的一项研究证实了B细胞清除疗法治疗活动性RA有效而且安全,并提示可能达到长期缓解,为患者带来新的希望,从而也进一步揭示了B细胞在RA发病机制中的重要作用。     

Symptoms in individuals at risk of rheumatoid arthritis

An increasing interest in treating individuals at risk of rheumatoid arthritis (RA) to prevent the development of this chronic condition has focussed attention on the identification of risk factors of this disease. Most patients who develop RA progress through a preceding symptomatic phase that may take the form of arthralgia, palindromic rheumatism or unclassified arthritis before a disease currently classifiable as RA is established. An understanding of symptoms that identify individuals as being at risk of RA is a critical issue. Constellations of relevant symptoms could (1) form the basis of public health campaigns to encourage rapid consultation, (2) inform primary health care providers regarding which patients to perform additional tests in or whom to refer to a rheumatologist and (3) be included in algorithms to predict RA development. In this review, we present qualitative and quantitative data summarising current understanding of the symptoms experienced by individuals at risk of RA.     

Gene therapy in rheumatic diseases

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation as well as progressive cartilage and bone destruction. Advances in the understanding of the pathophysiology of RA have led to the development of new therapeutic strategies, including gene therapy. Gene therapy offers a new approach to deliver therapeutic proteins to the joints of arthritis patients. Local as well as systemic gene therapy can be envisaged for the treatment of arthritis. Several viral and non-viral vectors have been used in animal models for rheumatoid arthritis for ex vivo and in vivo delivery of therapeutic genes. Promising pre-clinical data have resulted from the application of these strategies. Using ex vivo gene delivery, successful and safe gene transfer has been demonstrated in the joints of RA patients. Although new insights into the role of cytokines and other mediators of chronic inflammation have provided novel targets for therapeutic intervention, the development of vectors that induce long-term and regulated gene expression remains a challenge.     

类风湿关节炎骨吸收指标与关节破坏的相关性

类风湿关节炎是以慢性对称性多关节滑膜炎、骨及软骨破坏为主要特征的自身免疫性疾病,其发展过程中的骨代谢异常可导致不同程度骨量丢失和骨破坏,骨破坏的相关指标可反映骨量丢失的严重程度,并可预测疾病发展和关节破坏程度。本文对类风湿关节炎患者骨吸收相关指标与关节破坏相关性的最新进展进行综述。     

New-onset demyelination induced by infliximab therapy in two rheumatoid arthritis patients

Therapies aimed at inhibiting tumor necrosis factor, a proinflammatory cytokine implicated in autoimmune disease, are effective for rheumatoid arthritis (RA) and Crohn’s disease. We report two patients who newly developed multiple demyelinating lesions in the central nervous system in the course of infliximab therapy for active RA. Neurological symptoms and the number of gadolinium-diethylenetriamine pentaacetic acid-enhanced lesions in magnetic resonance imaging gradually diminished with steroid treatment.     

Engineering approaches to investigate the roles of lymphatics vessels in rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory joint disorders. While our understanding of the autoimmune processes that lead to synovial degradation has improved, a majority of patients are still resistant to current treatments and require new therapeutics. An understudied and promising area for therapy involves the roles of lymphatic vessels (LVs) in RA progression, which has been observed to have a significant effect on mediating chronic inflammation. RA disease progression has been shown to correlate with dramatic changes in LV structure and interstitial fluid drainage, manifesting in the retention of distinct immune cell phenotypes within the synovium. Advances in dynamic imaging technologies have demonstrated that LVs in RA undergo an initial expansion phase of increased LVs and abnormal contractions followed by a collapsed phase of reduced lymphatic function and immune cell clearance in vivo. However, current animal models of RA fail to decouple biological and biophysical factors that might be responsible for this lymphatic dysfunction in RA, and a few attempted in vitro models of the synovium in RA have not yet included the contributions from the LVs. Various methods of replicating LVs in vitro have been developed to study lymphatic biology, but these have yet not been integrated into the RA context. This review discusses the roles of LVs in RA and the current engineering approaches to improve our understanding of lymphatic pathophysiology in RA.     

Can rheumatoid arthritis be prevented?

The discovery of elevations of rheumatoid arthritis (RA)-related biomarkers prior to the onset of clinically apparent RA raises hopes that individuals who are at risk of future RA can be identified in a preclinical phase of disease that is defined as abnormalities of RA-related immune activity prior to the clinically apparent onset of joint disease. Additionally, there is a growing understanding of the immunologic processes that are occurring in preclinical RA, as well as a growing understanding of risk factors that may be mechanistically related to RA development. Furthermore, there are data supporting that treatment of early RA can lead to drug-free remission. Taken as a whole, these findings suggest that it may be possible to use biomarkers and other factors to accurately identify the likelihood and timing of onset of future RA, and then intervene with immunomodulatory therapies and/or risk factor modification to prevent the future onset of RA in at-risk individuals. Importantly, several clinical prevention trials for RA have already been tried, and one is underway. However, while our growing understanding of the mechanisms and natural history of RA development may be leading us to the implementation of prevention strategies for RA, there are still several challenges to be met. These include developing sufficiently accurate methods of predicting those at high risk of future RA so that clinical trials can be developed based on accurate rates of development of arthritis and subjects can be adequately informed of their risk of disease, identifying the appropriate interventions and biologic targets for optimal prevention, and addressing the psychosocial and economic aspects that are crucial to developing broadly applicable prevention measures for RA. These issues notwithstanding, prevention of RA may be within reach in the near future.     

Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune‐mediated inflammatory disease (IMID). We recently discovered that autonomic dysfunction precedes and predicts arthritis development in subjects at risk of developing seropositive RA. In addition, RA patients with relatively high vagus nerve tone (higher parasympathetic parameters, measured by heart rate variability) respond better to antirheumatic therapies. Together, these data suggest that the ANS may control inflammation in humans. This notion is supported by experimental studies in animal models of RA. We have found that stimulation of the so‐called cholinergic anti‐inflammatory pathway by efferent electrical vagus nerve stimulation (VNS) or pharmacological activation of the alpha7 subunit of nicotinic acetylcholine receptors (α7nAChR) improves clinical signs and symptoms of arthritis, reduces cytokine production and protects against progressive joint destruction. Conversely, increased arthritis activity was observed in alpha7nAChR knockout mice. These studies together with previous work in animal models of sepsis and other forms of inflammation provided the rationale for an experimental clinical trial in patients with RA. We could for the first time show that an implantable vagus nerve stimulator inhibits peripheral blood cytokine production in humans. VNS significantly inhibited TNF and IL‐6 production and improved RA disease severity, even in some patients with therapy‐resistant disease. This work strongly supports further studies using a bioelectronic approach to treat RA and other IMIDs.     

A型滑膜细胞与类风湿关节炎血管新生

类风湿关节炎(RA)是一种常见的多系统性炎症性自身免疫性疾病.RA最主要病理特征是关节滑膜血管新生和对关节破坏力极强的血管翳形成.血管的新生是个复杂的过程,多种细胞及其所分泌的细胞因子参与了此过程.近来大量的研究表明,A型滑膜细胞即滑膜巨噬细胞在RA病理过程中起着非常重要的作用,其参与了炎症和血管新生的整个过程.A型滑膜细胞表达黏附分子、趋化因子受体和多种表面抗原物质,还能分泌产生大量的细胞因子、生长因子和其它化学活性物质.它们在RA滑膜病理过程中起着关键性作用.因此,A型滑膜细胞可能将成为RA治疗很好的靶点.     

类风湿关节炎动脉粥样硬化的研究进展

类风湿关节炎是一种慢性自身免疫性疾病,主要损害外周关节滑膜,类风湿关节炎的致残率较高.近年来,心血管疾病作为其主要的死亡原因之一,引起人们越来越多的关注.绝大部分患者在心血管方面的改变以动脉粥样硬化为主,本文就与类风湿关节炎有关的动脉粥样硬化发病机制的研究进展作一综述.     

Rheumatoid Arthritis: A Role for Immunosenescence?

Aging is accompanied by a progressive decline in the integrity of the immune system, a process known as immunosenescence. Pathological features typical of immune dysfunction in older adults, encompassing dysregulation of innate and adaptive immune responses, characterize rheumatoid arthritis (RA), an autoimmune disease whose incidence increases with age. Recent evidence suggests that certain features of immunosenescence, such as the decrease in T-cell generation and diversity, may contribute to the development of RA. Thus, physiological immunosenescence may render older adults susceptible to RA, and premature immunosenescence may contribute to the development of RA in young adults. In addition, other features of immunosenescence may result from the chronic immune stimulation that occurs in RA and lead to worsening of the disease. This article reviews the immunopathological features common to aging and RA and discusses the mechanisms by which immunosenescence may contribute to the development or progression of RA.     

Estrogens in rheumatoid arthritis; the immune system and bone

Rheumatoid arthritis (RA) is an autoimmune disease that is more common in women than in men. The peak incidence in females coincides with menopause when the ovarian production of sex hormones drops markedly. RA is characterized by skeletal manifestations where production of pro-inflammatory mediators, connected to the inflammation in the joint, leads to bone loss. Animal studies have revealed distinct beneficial effects of estrogens on arthritis, and a positive effect of hormone replacement therapy has been reported in women with postmenopausal RA. This review will focus on the influence of female sex hormones in the pathogenesis and progression of RA.     

Is there a place for initial treatment with biological DMARDs in the early phase of RA?

The use of biological disease-modifying antirheumatic drugs (bDMARDs) has changed the face of rheumatoid arthritis (RA). Achieving remission, normal function and prevention of joint damage are now possible for many patients with RA. In clinical practice, however, particularly with cost considerations, bDMARDs are usually prescribed after failure of one or more conventional synthetic DMARDs. With evidence that early treatment has a greater impact than later on, the question regarding initial bDMARD therapy and their potential role within a window of opportunity to influence disease outcomes remain. The increasing emphasis on early diagnosis and research into the preclinical phase of the disease also heralds the question, ‘Can bDMARDs prevent the development of RA?’The aim of this review is to review randomised controlled trials with bDMARDs as initial therapy in early RA and to discuss their role in early disease.     

Nutritional status in rheumatoid arthritis

Background & aimsRheumatoid Arthritis (RA) is a chronic inflammatory autoimmune disease affecting the joints. It has been suggested that obesity increases the likelihood of RA development lowers the chance to achieve low disease activity and disease remission. The purpose of the study was to analyze the nutritional status of a cohort of persons with RA and compare to cohorts of persons with other arthritis and without.Methods and resultsWe used the NHANES database from 2015 to 2018, assessing anthropometric data, body composition, micronutrients, bone metabolism, protein content and laboratory data from those participants; and to compared to others without arthritis or with other forms of arthritis.We included 19,225 participants, with an estimation of population size of 637,323,765 and female preponderance of 52% and an average age of 38 ± 0,4 yrs. RA had an incidence of 4.5% and other arthritis (OA) of 15%.There was a higher prevalence of overweight and obesity, central obesity and percentage of body fat in RA and OA. Obesity related conditions such as dyslipidemia, diabetes, and hypertension were more prevalent in those participants. Fasting glucose levels, oral glucose tolerance test at 2 h, insulin levels and HbA1c were all significantly higher in persons with RA and OA.ConclusionThe higher prevalence of metabolic syndrome together with the inflammatory state of RA, constitute important cardiovascular risk factors, which should be addressed aggressively preferably by primary prevention.     

Rheumatoid arthritis induced by alpha-interferon therapy

Interferon (IFN) therapy has been used for the treatment of common diseases such as hepatitis C, myeloproliferative disorders, autoimmune diseases and various types of cancer. Given the biological properties of interferon, it is not surprising that there are a larger number of side effects due to its use. Although rheumatoid arthritis (RA) is one of the most common autoimmune diseases found in clinical practice, it does not seem to be frequently related to IFN therapy. We report a 40-year-old female patient who, after high doses of IFN-α therapy for malignant melanoma, developed symmetrical polyarthritis, with pain and oedema in small and large joints, associated with prolonged morning stiffness. She had positive rheumatoid factor and DR4 HLA phenotype. She was treated with deflazacort (6 mg/day), chloroquine and NSAIDs, with a partial response. In conclusion, although the development of RA after IFN therapy is a rare event, IFN may work as a ‘trigger’ for such complication, leading to deregulation in the immune cascade in a person genetically predisposed. Received: 20 October 2000 / Accepted: 31 January 2001     

A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corticosteroid and low‐dose methotrexate

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid‐induced diabetes mellitus who was taking corticosteroid and low‐dose methotrexate.     

Serious liver disease induced by infliximab

Infliximab, a chimeric monoclonal antibody that binds the tumor necrosis factor α (TNFα), is used in the treatment of rheumatoid arthritis (RA) and Crohn’s disease (CD). Previous cases of significant secondary liver disease associated with infliximab treatment have been reported in patients with RA, CD, and psoriatic arthritis. Two additional patients with RA who developed a serious liver disease associated with infliximab treatment are reported here. A 39-year old RA patient was admitted with cholestatic liver disease after 8 months of treatment with infliximab. She had no history of hepatic diseases, exposure to hepatotoxic or illicit drugs, or alcohol abuse. A liver biopsy showed severe ductal proliferation with collapse and enucleation of the hepatocytes. Despite aggressive treatment with oral prednisolone, she developed hepatic failure. On the 45th day, a liver transplant was performed. The second patient, a 54-year old RA patient, was diagnosed with autoimmune hepatitis after 12 infliximab infusions. She fulfilled autoimmune hepatitis type 1 criteria. A liver biopsy disclosed an altered lobulillar structure with chronic inflammation and the formation of collagen bands. She was treated with prednisolone and azatioprine and a complete recovery was noted 1 month later. These cases should alert rheumatologists to the possibility of new adverse reactions (liver injury) associated with the use of TNFα blockers in an autoimmune setting.     

白细胞介素-6阻断剂在类风湿关节炎的治疗应用

类风湿关节炎(rheumatoid arthritis,RA)是一种系统性炎症性自身免疫性疾病。免疫系统的失调在其发病中起着重要作用,因而抑制炎症反应是治疗RA的重要手段。白细胞介素6(interleukin-6,IL-6)是多功能细胞因子,与RA的发病有着密切联系。阻断IL-6信号传导通路是RA治疗的一个新策略。托珠单抗(Tocilizumab)是人源化IL-6受体单克隆抗体,一系列随机双盲安慰剂对照临床试验已显示其对于RA患者的疗效和安全性。这一药物可能会为RA的治疗带来新的曙光。