Circulating and intra-articular immune complexes in patients with rheumatoid arthritis. Correlation of 125I-Clq binding activity with clinical and biological features of the disease.

The correlation between the incidence and level of immune complexes in serum and synovial fluid and the various clinical and biological manifestations of rheumatoid arthritis has been studied. Immune complexes were quantitated using a sensitive radioimmunoassay, the 125I-Clq binding test, in unheated native sera and synovial fluids from 50 patients with seropositive (RA +) and 45 with seronegative (RA -) rheumatoid arthritis, 17 with other inflammatory arthritis, and 37 with degenerative and post-traumatic joint disease. The following observations were made: (a) when compared to the results from patients with degenerative and post-traumatic joint diseases, the 125I-Clq binding activity (Clq-BA) in synovial fluid was found to be increased (by more than 2 SD) in most of the patients with RA + (80%) and RA - (71%) and in 29% of patients with other inflammatory arthritis; the serum Clq-BA was also frequently increased in both RA + (76%) and RA - (49%) patients, but only exceptionally in patients with other inflammatory arthritis (6%); (b) a significant negative correlation existed between the Clq-BA and the immunochemical C4 level in synovial fluids from patients with RA + and RA -; (c) neither the serum nor the synovial fluid Clq-BA in rheumatoid arthritis significantly correlated with the erythrocyte sedimentation rate, the clinical stage of the disease, or the IgM rheumatoid factor titer; and (d) the serum Clq-BA in patients with rheumatoid arthritis and extra-articular disease manifestations (40 +/- 34% in those with RA +,32 +/- 29% in those with RA -) was significantly increased as compared to the serum Clq-BA in patients with joint disease alone (24 +/- 30% in those with RA +, 10 +/- 13% in those with RA -). Experimental studies were carried out in order to characterize the Clq binding material in rheumatoid arthritis. This material had properties similar to immune complexes: it sedimented in a high molecular weight range on sucrose density gradients (10-30S) and lost the ability to bind Clq after reduction and alkylation, or after acid dissociation at pH 3.8, or after passage through an anti-IgG immunoabsorbant. DNase did not affect the Clq BA. These results support the hypothesis that circulating as well as intra-articular immune complexes may play an important role in some pathogenetic aspects of rheumatoid arthritis. The 125I-Clq binding test may also be of some practical clinical value in detecting patients who have a higher risk of developing vasculitis.     

Nomenclature for the Phases of the Development of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common immune-mediated inflammatory disease. Research on RA is increasingly focused on the earliest stages of the disease, and has provided strong evidence that clinical signs and symptoms may be preceded by a preclinical phase during which evidence of systemic autoimmunity may be present. To facilitate research in this area, a number of international initiatives have proposed definitions of the phases of disease leading up to RA. The first of these initiatives was the European League Against Rheumatism's (EULAR) set of recommendations on terminology in persons at risk for RA, which suggested that the "at-risk phases" be described in terms of patients variably having: (A) genetic risk factors for RA; (B) environmental risk factors for RA; (C) systemic autoimmunity associated with RA; (D) symptoms without clinical arthritis; and (E) unclassified arthritis. The phrase clinically suspect arthralgia (CSA) is now widely used and can be regarded as describing a subgroup of patients in phase D. A definition of CSA was recently proposed by a EULAR taskforce, and primary research has begun to explore the full range of symptoms, as well as their sensitivity and specificity alone and in combination with other factors, that characterize this phase. Similarly, immune abnormalities at mucosal and others sites that precede and/or are associated with the onset of musculoskeletal symptoms are being increasingly studied and understood. Whether some of these at-risk phases, in particular CSA, represent entities meriting their own classification criteria is an essential area for consensus and will be discussed.     

The characteristics of the course of inflammatory joint diseases in the inhabitants of an agricultural region]

The course of the main chronic inflammatory diseases of the joints was analyzed with special reference to the rural region of Georgia. 30 patients with rheumatoid arthritis (RA), 13 with ankylosing spondylarthritis, and 6 with reactive arthritis are registered and followed up by the rheumatologist. It is shown that the population of the region in question is characterized by a later onset of RA, a high percentage of the seronegative variety of the disease with involvement of the hand joints, and ankylosing of the carpal joints. The males demonstrate a low activity of the process. Since RA ran a benign course, the patients were only treated with nonsteroidal anti-inflammatory agents. The RA patients preserved work fitness for a long time. Ankylosing spondylarthritis was marked by the primary injury to the spine associated with the development of ankylosis and calcification of the ligamentous apparatus without a well-defined spinal deformity. Large-scale examination of the population of the region has shown the necessity of such measures for they permit identification of new cases of the disease to carry out early adequate treatment and specialized employment of the patients.     

Abnormally-fucosylated serum haptoglobins in patients with inflammatory joint disease

The fucosylation of haptoglobins is altered in rheumatoid arthritis. In order to investigate the clinical usefulness of this finding, serum levels of abnormally-fucosylated haptoglobins (FHp) have been assessed in defined and matched groups of patients with different inflammatory joint diseases. FHp was elevated in 16/17 patients with active rheumatoid arthritis (RA); 1/20 patients with inactive rheumatoid arthritis; 1/11 patients with osteoarthritis; and 4/10 patients with seronegative polyarthritis. Raised FHp levels, therefore, are not disease-specific. There was no relationship between the duration of RA and the FHp level. The FHp expression in RA was also compared with other biochemical indices of disease activity. The degree of correlation between FHp and articular index, joint score and early-morning stiffness was very similar to that obtained for C reactive protein (CRP), and better than that obtained for erythrocyte sedimentation rate and haemoglobin. FHp, however, gives fewer false-positives than CRP in cases of inactive disease. until FHp can be measured more easily and cheaply, CRP estimation is still the biochemical test of choice in RA.     

Self-helplessness in arthritis: an important but overlooked index

The recent introduction of patient-reported outcome measures (PROMs) assessment into rheumatology practice has changed the way patients suffering from inflammatory arthritis are assessed. This article describes a cross-sectional study of 102 rheumatoid arthritis (RA) patients that was undertaken to evaluate the construct of helplessness in patients with RA, its correlation with other disease activity parameters, and its sensitivity to change following biologic therapy. The study also set out to explore the possibility of including a self-helplessness measurement, using the modified Rheumatology Attitude Index (mRAI), as part of the holistic patient assessment in standard clinical practice. Assessment of self-helplessness was shown to be significantly correlated with both psychological as well as functional status measures. The mRAI index is a highly useful and predictive tool for clinical use that is responsive to change in the patients' clinical condition. As part of the PROMs questionnaire, this scale can be applied in a manner similar to other indicators of disease activity status, and is as easy to administer and interpret in standard clinical practice.     

HL-A antigens in psoriasis with special reference to the clinical type, age of onset, exacerbations after respiratory infections and occurrence of arthritis.

HL-A typing was performed in a series of 125 patients with common psoriasis, 12 patients with flexural psoriasis, 16 patients with erythrodermic psoriasis and 16 patients with generalized pustular psoriasis, and compared with typing in a control population. The HL-A antigens 13 and 17 were significantly increased in patients with common psoriasis and erythrodermic psoriasis. HL-A 17 was also found in two of the 16 patients with generalized pustular psoriasis. Neither HL-A 13 nor 17 was increased in patients with flexural psoriasis. It is suggested that flexular psoriasis might be genetically distinct from common psoriasis. TY was increased in patients with common psoriasis. The increase of HL-A 13, 17 and TY was most marked in patients with onset of psoriasis before the age of 40 years. HL-A 13 was found in 38 per cent of the 40 patients with infection-related exacerbations of psoriasis, but only in 17 per cent (p = 0.012) of the remaining 129 patients. HL-A 27 was found in 58 per cent of the 26 patients with sacro-iliitis and in 27 per cent of the 41 patients with peripheral arthritis without sacro-iliitis, but only in eight per cent of the 102 non-arthritic patients (p less than 0.001) and p less than 0.01, respectively).     

Abatacept: the first T lymphocyte co-stimulation modulator, for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a multisystem autoimmune disease, of unknown aetiology with high morbidity and significantly increased mortality. Over recent years, the introduction of targeted therapies with biologic agents have made major inroads to the outcomes in RA. The first such agents developed were TNF-alpha inhibitors. However, despite their high efficacy, up to 30% patients fail to respond adequately, or develop adverse reaction to TNF-alpha inhibitors. This suggests that other pathological mechanisms are involved, in addition to those mediated by TNF-alpha. Abnormal T-cell function has long been thought to play a key role in the pathogenesis of RA, stimulating both the production of pro-inflammatory cytokines and recruitment of other inflammatory cells, resulting in joint destruction and systemic disease. Abatacept, the first of a group of T-cell co-stimulation modulators, targeting T-cell activation, has recently been licensed for use in RA and shows promise as a useful drug to treat this major disabling disease.     

Evolution of seronegative arthritis

The paper is concerned with the results of a follow up of 67 patients with seronegative arthritis. The average duration of observation was 7.6 yrs. Diagnoses in 4 patients were established on a repeated clinicolaboratory and x-ray study: ankylosing spondylitis, Reiter's syndrome, Yersinia arthritis and gonorrheal arthritis. A picture of seropositive rheumatoid arthritis was noted in 16 patients (24%). In 47 patients arthritis remained seronegative. Of them in 30 patients a course of disease did not differ from that of seropositive rheumatoid arthritis. Considerable progression of disease was noted at the acute onset of disease with multiple involvement of the joints and a high inflammatory and immunological activity of a process. A morphological investigation of the synovial bioptates in 20 patients did not reveal a classical picture of rheumatoid synovitis even in a prolonged course of seronegative rheumatoid arthritis. The authors defined two variants of morphological changes in the synovial tissue in this group corresponding to a benign and progressive course of seronegative RA.     

Persistence of various infective agents in blood mononuclear leukocytes in a debut of rheumatoid arthritis

AIM: To study persistence in blood mononuclear leukocytes (ML) of Herpesviridae viruses (cytomegalovirus-CMV, herpes virus of type I and II, Epstein-Barr virus-EBV, hepatitis B and C viruses, Mycoplasma arthritidis-Ma,, Mycoplasma fermentans-Mf, Ureaplasma urealiticum-U, Chlamydia trachomatis-Ct). MATERIAL AND METHODS: 56 patients with debut of rheumatoid arthritis (RA) and 30 healthy persons were examined using methods of direct and indirect immunofluorescence, polymerase chain reaction and enzyme immunoassay. RESULTS: In patients with early RA persistence of infective agents in blood ML was found high (67.9%). Persistence of the viruses was studied for 1.5-2 years. Features of the clinical course of the disease were specified for various infective agents: seronegativeness in persistence of Ma, Mf and U, high activity and frequent development of systemic manifestations of RA in persistence of Herpesviridae viruses, rapid progression of bone destruction in persistence of Ct. CONCLUSION: Carriage of Herpesviridae was associated with high activity of inflammatory process, of chlamydia--with rapid bone destruction, of mycoplsma and ureaplasma--with unchanged rate of progression. Eradication of Herpes viruses, CMV, EBV and CT is indicated.     

Aflibercept in lung cancer

Rheumatoid arthritis (RA) is a multisystem autoimmune disease, of unknown aetiology with high morbidity and significantly increased mortality. Over recent years, the introduction of targeted therapies with biologic agents have made major inroads to the outcomes in RA.The first such agents developed were TNF-α inhibitors. However, despite their high efficacy, up to 30% patients fail to respond adequately, or develop adverse reaction to TNF-α inhibitors. This suggests that other pathological mechanisms are involved, in addition to those mediated by TNF-α. Abnormal T-cell function has long been thought to play a key role in the pathogenesis of RA, stimulating both the production of pro-inflammatory cytokines and recruitment of other inflammatory cells, resulting in joint destruction and systemic disease. Abatacept, the first of a group of T-cell co-stimulation modulators, targeting T-cell activation, has recently been licensed for use in RA and shows promise as a useful drug to treat this major disabling disease.     

血液流变性与类风湿性关节炎的关系── 针刺活血化瘀效应观察

本文通过对３１例类风湿性关节炎患者的临床观察和假借ＲＡ大鼠模型的实验研究，并运用整体和局部治疗相结合的针刺方法，发现：绝大部分ＲＡ患者有血液流变学异常，有统计学差异；模型组大鼠有血液流变学异常和血小板聚集率增高，有统计学差异．提示（１）血流变学的异常与本病的发生发展有一定关系；（２）针刺具有活血化瘀作用；（３）血液流变学检查可作为ＲＡ活动程度及疗效评定标准之一．     

Rheumatoid arthritis in Lithuania: need for external help from the onset of disease

PURPOSE: To estimate the burden of rheumatoid arthritis (RA) in Vilnius, Lithuania, the former socialist country in Eastern Europe, in terms of patients' need for help from other persons and to explore the factors which influence the need for physical help. METHOD: Some 537 patients with RA, registered in Vilnius, answered questions about socio-demographics, disease characteristics, categories of required help, the use of major appliances and adaptations, underwent a clinical examination and filled in the modified health assessment questionnaire (MHAQ) and arthritis impact measurement scale (AIMS). Logistic regression was used to assess which variables from those explored influenced the need for physical help. RESULTS: A total of 230 (42.9%) patients out of 537 were requiring help from other persons, and the proportion was equally high in all the disease duration categories. A quarter of the patients (25.1%) were classified to ACR III and IV functional impairment groups. In multivariate logistic regression model the risk to become dependent on external help ultimately depended on MHAQ (10.32 [CI 95% 6.57; 16.23], p < 0.001) but the use of joint stabilization measures (1.97 [CI 95% 1.06; 3.64], p < 0.01) and 28 tender joints count (1.02 [CI 95% 1.0; 1.06], p < 0.05) were also important. CONCLUSIONS: Nearly half of the patients reported being dependent on others and a quarter of patients were in definite need for that. The functional impairment is the most important risk factor, although identifying the group using joint stabilization measures routinely may be of practical value in order to define the risk group which may need the external help in future.     

Rheumatoid arthritis: a primary care approach

PURPOSE: To provide primary care providers with guidelines on the evaluation, diagnosis and management of patients with rheumatoid arthritis (RA). DATA SOURCES: Research-based articles in the medical literature, review articles, and clinical practice is a chronic inflammatory disease that affects mainly synovial joints. Diagnosis is based primarily on clinical examination. Clinical criteria developed by the American Rheumatism Association can help the primary care provider recognize this potentially devastating disease and facilitate early referral to a rheumatologist for treatment. IMPLICATIONS FOR PRACTICE: Patients with RA should be treated early and aggressively. Laboratory tests are not essential to confirm the diagnosis of RA. The clinical usefulness of the rheumatoid factor could be increased by restricting the test to patients who have a high probability of RA based on clinical symptoms.     

Immune reactions with streptococcal antigens and homologous myocardial tropomyosin in rheumatoid arthritis with visceritis

A humoral and cellular immune response to polysaccharide and protein antigens of the cell wall of streptococci (Groups A, B, C and G) and to homologous myocardial tropomyosin was studied in patients with rheumatoid arthritis (RA) with different clinical variants of disease and in healthy persons. In RA patients humoral and cellular immune reactions to polysaccharide and protein streptococcal antigens were especially marked with the use of the structural components of the cell wall of streptococcus, Group B. Elevated titers of antibodies to homologous myocardial tropomyosin were detected in RA patients as compared to those in a group of healthy persons, an average titer of antibodies to tropomyosin in RA patients with systemic symptoms being much higher than in patients with an articular form of disease. The authors emphasized a possible role of antigens of the cell wall of streptococcus, Group B, in the occurrence and development of immunopathological reactions in RA, and a role of antibodies to myocardial tropomyosin in immunopathogenesis of cardiac disorder in this disease.     

Keishibukuryogan (gui-zhi-fu-ling-wan), a Kampo formula, decreases disease activity and soluble vascular adhesion molecule-1 in patients with rheumatoid arthritis

An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS(28)). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS(28) decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients.     

Evaluation of rheumatic disorders in patients with primary biliary cirrhosis

Twenty-six consecutive patients with primary biliary cirrhosis (PBC) were subjected to clinical, radiological and serological assessment for evidence of rheumatic disease. Seven patients had asymptomatic liver disease, while the rest had symptoms indicating varying stages of advanced disease. Of the 18 patients with arthropathy, in 13 there was considered to be an association between the arthropathy and PBC as no other underlying causes could be discovered. In about half of the patients the symptoms were episodic, while the others had chronic pain. Usually both large and small joints were affected bilaterally. The joint symptoms had an average duration of 5 years, and had started in all patients after the onset of the liver disease. All 7 patients with arthritis fulfilled the criteria of the American Rheumatism Association for rheumatoid arthritis (RA). Five patients were classified as definite or classical RA. Circulating immune complexes were present in 35% of all patients, but there was no correlation with the presence of arthropathy. Seven patients were HLA-B27 positive, of whom 4 had arthritis. The investigation demonstrates that rheumatic disorders are common in PBC patients, whether or not they are symptomatic, and sometimes joint symptoms may even dominate the clinical picture.     

2013年风湿免疫病学主要临床进展

风湿免疫病学科是内科领域最年轻的学科,但也是发展速度最快的学科之一.每年都有多种疾病治疗指南得到更新.2013年,类风湿关节炎(RA)新的治疗指南仍将传统合成改变病情抗风湿药物(csDMARDs)作为一线治疗方案,不再推荐生物制剂作为一线治疗,而是作为csDMARDs治疗反应不佳的RA患者的二线选择.应用生物制剂治疗前后均应高度重视结核病筛查与预防性治疗.关节超声、磁共振成像检查有助于诊断不典型RA、预测进展型未分化炎症性关节炎、了解疾病活动度、评估预后和治疗反应等.侵蚀性关节炎有了明确定义.部分系统性红斑狼疮(SLE)患者有望接受少或无激素治疗,生物制剂在SLE中的应用也初显端倪.尽管SLE患者预后显著改善,但心血管疾病、抑郁症、骨质疏松和骨折等合并症患病率显著增高.放射学阴性中轴型脊柱关节炎(SpA)概念的提出和系统性硬化病(SSc)分类标准的更新,显著提高了SpA和SSc的早期诊断率."达标治疗"方案成为高尿酸血症和痛风的目标治疗策略,特别是反复发作的痛风患者血尿酸水平应长期控制在300 μmol/L以下.     

The level of R proteins in reactive arthritis

A total of 46 patients with reactive arthritides and 20 patients with rheumatoid arthritis (RA) were examined, as compared with 20 normal persons, for the blood serum content of the products of catabolic breakdown of cell receptors--R proteins (according to inhibition of the hemagglutination reaction between human red blood cells and anti-R-serum) and for conventional parameters of phagocyte function of leukocytes. The content of R proteins in patients with reactive arthritis and RA was found to be increased, and the phagocytic activity was discovered to be lowered. The changes in the parameters indicated depended on the disease entity and the disease course. The possible pathophysiological importance of changes in the level of R proteins in arthritides is discussed.     

Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: a review

Osteoarthritis (OA) of the knee and hip is a debilitating disease affecting more women than men and the risk of developing OA increases precipitously with aging. Rheumatoid arthritis (RA), the most common form of inflammatory joint diseases, is a disease of unknown etiology and affects approximately 1% of the population worldwide, and unlike OA, generally involves many joints because of the systemic nature of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs of choice for the symptomatic treatment of both OA and RA. Because of the risks associated with the use of NSAIDs and other limitations, the use of alternative therapies, such as acupuncture and medicinal herbs, is on the rise and according to reports approximately 60-90% of dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine (CAM). This paper reviews the efficacy of some of the common herbs that have a history of human use and their anti-inflammatory or antiarthritic properties have been evaluated in animal models of inflammatory arthritis, in studies employing well defined and widely accepted in vitro models that use human chondrocytes/cartilage explants or in clinical trials. Available data suggests that the extracts of most of these herbs or compounds derived from them may provide a safe and effective adjunctive therapeutic approach for the treatment of OA and RA. This, in turn, argues for trials to establish efficacy and optimum dosage of these compounds for treating human inflammatory and degenerative joint diseases.