Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7785487 | The pathogenesis of rheumatoid arthritis and the development of therapeutic strategies for | 1995 | This review discusses current concepts of the pathogenesis of rheumatoid arthritis. It is proposed that RA is a T cell mediated disease following which a large number of subsequent inflammatory events are unleashed. Many of the pathogenetic steps are targets for new therapies including biologics. Laboratory, clinical and radiological methods of assessing disease activity are sufficiently sensitive and reproducible to permit their use in multicentre studies capable of detecting a biologic with disease modifying activity. The clinical assessment of the efficacy and toxicity of biologics poses unique problems. These have been illustrated by the example of 3 monoclonal antibodies directed against ICAM-1, CD4 and TNF alpha. The main role of most biologics may be to pinpoint important therapeutic targets which can be attacked by more easily administered and less costly xenobiotic drugs. | |
| 8981860 | Coping with rheumatoid arthritis. How can specialist nurses influence it and promote bette | 1996 Nov | Psychological stressors are said to be an important influence on the outcome of chronic illness such as rheumatoid arthritis (Engel, 1977). Helping patients to cope with stressors is identified as a central concept in the delivery of nursing care (Khan et al., 1994). It is thus reasonable to suggest that rheumatology nurses may be key players in the process of coping with rheumatoid arthritis. But in order for rheumatology nurses to be effective players in this process, they need to discourage coping behaviour(s) linked to poor outcomes, and/or promote an overall behaviour pattern linked to a better outcome. Literature showing the link between different coping behaviours and outcome is examined, and cognitive restructuring is emphasized as one method nurses could use. Having identified coping behaviour which is optimal in terms of future outcome, further study of different forms of coping-based educational intervention is suggested, to reveal how such patterns of behaviour can be taught by nurses in the most effective way. | |
| 7638113 | [Can the prognosis of early rheumatoid arthritis be predicted?]. | 1995 May 20 | Rheumatoid arthritis is a frequently and potentially severe disease which causes a functional handicap in nearly half the patients 10 years after the identification of the first clinical manifestations. Some patients develop very severe forms with joint destruction and multiple organ involvement while in others the disease remains benign, even after a long clinical course of several years. Theoretically, the future intensity of rheumatoid arthritis in a given patient cannot be predicted at the time of early diagnosis. No prognosis factor has been identified and universally accepted and validated. A marker of prognosis would be highly appreciated by clinicians who could then more closely adapt their management decisions to the disease potential. Clinical and biological data collected to date have provided a limited amount of prognostic information but recent progress in molecular biology suggests that genetic markers could be correlated with disease severity. Several HLA-DRB1 alleles including DR1*0401, DRB1*0404, DRB1*0101 and sometimes DRB1/1001 and DRB1/1402 are potential markers. In France 85% of the patients with rheumatoid arthritis have one of these genes compared with 25% in the general population. In patients with a "high risk" alleles, the second haplotype could also have prognostic value. It would appear possible to distinguish immunogenetically homogeneous subpopulations corresponding to the more severe forms of the disease. It is still too early to propose therapeutic strategies based on current prognosis markers, but a combination of the most pertinent markers should be already used to select homogeneous subsets of patients in fundamental research and clinical trials. | |
| 1617891 | The role of pregnancy in the course and aetiology of rheumatoid arthritis. | 1992 Jun | The aetiology of rheumatoid arthritis (RA) is unknown, although being female is generally recognized as the most important independent risk factor, the disease being 2 to 3 times more frequent in females than in males. The dramatic effect of pregnancy in rheumatoid arthritis has been documented for over 50 years. This review examines the evidence and possible mechanisms by which pregnancy modifies the disease process and may alter predisposition to the development of RA in later life. | |
| 1503613 | The case for early intervention in rheumatoid arthritis. | 1992 Apr | A case for early intervention in rheumatoid arthritis is presented on the basis of the following observations: (1) established rheumatoid arthritis of 5 years duration or more is a progressive disease in most patients; (2) most patients with rheumatoid arthritis already have evidence of permanent radiographic damage within the first 2 years of disease; (3) the morbidity and mortality of rheumatoid arthritis are predicted by baseline data indicating more severe clinical status, rather than drug toxicity or causes 'unrelated' to rheumatoid arthritis; (4) currently used therapies, even those documented to be effective in randomized controlled trials, are not effective in most patients over periods of 2 years or longer. It is not known whether earlier intervention will result in better outcomes. However, these phenomena suggest a need for studies to evaluate early aggressive intervention in rheumatoid arthritis. | |
| 7839158 | The value of C-reactive protein measurement in rheumatoid arthritis. | 1994 Oct | Since 1973, assessment of serum concentrations of C-reactive protein (CRP) has been advocated as a objective measure of disease activity in rheumatoid arthritis (RA). Our review of clinical experience with CRP measurement suggests it has at least two important roles to play in the management of RA. First, persistently elevated CRP levels have prognostic value. In general, such elevated levels are found in those patients who are at greater risk for continuing joint deterioration and therefore may need more aggressive treatment and supportive care. Second, in general, improvement in CRP levels is an objective indication that a drug has produced a beneficial effect and thus may be useful to the physician for monitoring effects of therapy. Since CRP may be elevated in a number of conditions besides RA, a diagnosis of RA must be made before using CRP as a prognostic factor. | |
| 7600066 | Rheumatoid arthritis and filaggrin. A review. | 1995 Feb | The most specific markers for rheumatoid arthritis are antibodies to keratinized epithelia, namely antiperinuclear factor, whose antigen target in human oral mucosal cells has exactly the same distribution as profilaggrin, and anti-rat esophagus antibodies directed against human filaggrin. In this review, we will discuss the large body of data on the nature and physiology of profilaggrin and filaggrin that has accumulated since the profilaggrin gene was cloned. The possible mechanisms and significance of loss of B-cell tolerance to filaggrin in patients with rheumatoid arthritis are examined. | |
| 7638118 | [Rheumatoid arthritis: its relationship with HLA DR molecules]. | 1995 May 20 | Over the last two decades, much progress has been made in our understanding of the genetics of rheumatoid arthritis since the discovery of a link between the HLA DR4 antigen and rheumatoid arthritis in 1974. In molecular biology, the precise alleles of the HLA DRB1 gene which encode for different specific molecules have been identified. They have been used to link rheumatoid arthritis to certain HLA DRB1 subtypes recognized as "high risk" alleles. It has been hypothesized that the shared epitope would be one way for a molecular approach to susceptibility of allelic variants in rheumatoid arthritis. More recently, the notion that high risk DRB1 alleles might contribute to disease severity has also been put forward. HLA DRB1 alleles carrying a risk of rheumatoid arthritis would have two properties: they could serve as a marker of the risk of developing the disease and of disease severity both essential elements for the clinician. | |
| 1599815 | Mechanisms of tissue destruction and cellular activation in rheumatoid arthritis. | 1992 Jun | Rheumatoid arthritis is a chronic inflammatory disease of unknown etiology that is marked by synovial inflammation and destruction of articular extracellular matrix. Several studies of the pathogenesis of tissue destruction have focused on the production of metalloproteinases and their inhibitors in synovium as determinants of joint preservation. Also, the role of cytokines in the perpetuation of synovitis and of superantigens in synovial T-cell activation have led to novel hypotheses that attempt to explain abnormalities of synovial structure and function in rheumatoid arthritis. Recent studies that dealt with these topics are briefly reviewed in the context of current paradigms of inflammatory synovitis. | |
| 10163525 | Rheumatoid arthritis of the cervical spine. | 1995 Jul | There is a high incidence of cervical involvement in patients with rheumatoid disease. Early evaluation of the neck, close follow-up with dynamic radiographs of the cervical spine, and careful neurological assessment are important in the care of these patients. Surgical stabilization should be considered early even in the absence of neurological findings when significant instability is noted since outcome is related to preoperative neurological function. The type of fusion performed is determined by a careful assessment of the location of instability, patient factors, and the experience of the surgeon with various techniques. The type of postoperative immobilization should be decided on an individual basis depending on the quality of fixation achieved at surgery. Patients must be observed closely in the postoperative period for development of early complications and followed-up for the appearance of pseudarthrosis or late instabilities. | |
| 8016413 | Predictors of worsening clinical variables and outcomes in rheumatoid arthritis. | 1994 May | Predictors of disease activity severity and outcome have both been reviewed. Although data to date have usually examined one predictor at a time, it is likely that a combination of genetic factors (HLA-DR4 or its subsets), joint tenderness or swelling, RF positivity, presence of erosions early in disease, and gender can be combined to predict disease activity/severity. The precise "mix" and contribution of these factors, however, still needs to be determined. Longer-term functional outcome can best be predicted by accounting for baseline functional disability (which reflects disease activity/severity), disease severity per se, and psychologic variables (such as depression). Again, the precise variables of most importance still need some research. Finally, mortality appears to be predicted by functional factors (thus also by disease severity), but medications (e.g., prednisone), social factors, and age (not surprisingly) also contribute to mortality. | |
| 9122716 | Molecular mechanisms to form leukocyte infiltration patterns distinct between synovial tis | 1996 | There is a striking difference in the leukocyte infiltration pattern between synovial tissue and fluid of rheumatoid arthritis, a monocyte/macrophage-predominant infiltration in the former and a polymorphonuclear leukocyte (PMN)-predominant one in the latter. In extracts of rheumatoid arthritis synovial tissue, there is a strong chemotactic activity to monocytes but a negligible one to PMNs. The monocyte-specific chemotactic factor in the extracts represents dimers (and oligomers) of the S19 ribosomal protein which are cross-linked by a transglutaminase-catalyzed reaction. This oligomer formation may correlate to apoptosis in the lesion. On the other hand, in the synovial fluids there is the co-presence of chemotactic factors effective on PMNs as well as on monocytes and a strong chemotaxis inhibitor specific to monocytes. This inhibitory molecule is C4a which is liberated from complement component 4 in the presence of immune complexes. C4a exhibits its inhibitory activity indirectly by stimulating monocytes to release an autocrine or paracrine inhibitory cytokine to monocyte chemotaxis. These molecular mechanisms seem at least partly to cause the two distinct patterns of leukocyte infiltration in rheumatoid arthritis. | |
| 8310083 | Diagnosis and treatment of rheumatoid arthritis. | 1993 Dec | Rheumatoid arthritis is a chronic, inflammatory, connective-tissue disease that has well-defined clinical and laboratory characteristics. The management of rheumatoid arthritis requires an aggressive multidisciplinary treatment combining both pharmacologic and nonpharmacologic measures. Using this approach, most patients with rheumatoid arthritis can maintain their functional capacity while having their pain and suffering relieved. | |
| 8916297 | Role of cytokines, acute-phase proteins, and chemokines in the progression of rheumatoid a | 1996 Oct | Rheumatoid arthritis (RA) has no firm etiologic basis. It progresses as an autoimmune disease and evolves into a chronic inflammatory joint disease complicated by recurrent episodes of systemic acute-phase reactions, which sometimes result in amyloidosis. Cytokines play a pivotol role in inflammation and the immune response. Proinflammatory cytokines such as interleukin-1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 are present at high levels in arthritic joints, and their blood concentration correlates with the severity of the RA. Some of the activities of the proinflammatory cytokines, such as stimulation of leukocyte infiltration and release of their proteolytic enzymes, may be mediated by acute phase proteins (APPs), such as C-reactive protein and serum amyloid A, and by chemokines such as interleukin-8. Cytokines, chemokines, and APPs reciprocally regulate each others' expression and activities, constituting a communication network between fibroblasts, macrophages, lymphocytes, and hepatocytes. Activation of the network results in inflammation and the progressive destruction of joints and systemic symptoms characteristic of RA. | |
| 8343375 | Rheumatoid arthritis: effects on the family. | 1993 Jun 16 | The impact of rheumatoid arthritis (RA) on the families of people with the disease is poorly understood. A qualitative study was undertaken on 22 patients with rheumatoid arthritis, their respective well partners and their 40 children. For most children the effect of living with a parent suffering from a painful, chronic illness was not detrimental, but a minority suffered verbal and physical abuse. The disease had wide-ranging effects on sexual and working relationships, but marriage to a partner with RA did not result in a threat to the relationship for the majority. Recommendations for future practice are made. | |
| 8796983 | Pathways to gene therapy in rheumatoid arthritis. | 1996 May | Gene therapy offers novel possibilities for the treatment of rheumatoid arthritis. Present research is directed toward harnessing gene transfer technology to deliver genes whose products possess antiarthritic properties; the current emphasis is on transferring genes encoding secreted proteins. Genes may be delivered locally to individual diseased joints or systemically to extra-articular sites where the secreted gene products may enter the circulation. Local delivery is more laborious and unlikely to address systemic components of rheumatoid arthritis but should avoid side effects. Either ex vivo or in vivo strategies may be used to deliver the genes to the target tissues. Ex vivo techniques are more cumbersome but safer, because all genetic manipulations occur outside the body and cells may be extensively screened prior to implantation. A variety of vectors, including retrovirus, adenovirus, herpes simplex virus, and liposomes, as well as naked DNA, have been tested for their ability to deliver genes to joints. At the present stage of vector development, adenovirus seems best suited for in vivo gene delivery to synovium, but several authors have noted an inflammatory response, resulting in loss of gene expression. Ex vivo gene transfer using a retrovirus encoding human interleukin-1 receptor antagonist has succeeded in obtaining high intra-articular transgene expression with promising antiarthritic effects in animal models. Based on these data, the first human gene therapy trial for arthritis has been approved by the US Food and Drug Administration and will begin shortly. | |
| 7732162 | Refractory rheumatoid arthritis. Therapeutic options. | 1995 Feb | Because rheumatoid arthritis rarely remits, refractory disease is common. Attention should be paid to aggravating comorbid conditions. Pharmacologic options currently available include cyclosporin, high-dose methotrexate, combination second-line agents, and creative use of corticosteroids. The available literature is reviewed in this article and the potential risks and benefits of the various options are discussed. | |
| 8842713 | Medical aspects of rheumatoid arthritis. Diagnosis and treatment. | 1996 Aug | Rheumatoid arthritis commonly affects the hand and wrist. The differential diagnosis of inflammatory conditions affecting the hand is broad. A proper diagnostic approach necessitates a thoughtful interpretation of the presenting clinical features, laboratory tests, synovial fluid analysis, and radiographic data. Early, aggressive medical therapy with a combination of antiinflammatory and remittive agents may reduce mortality in selected patients and prevent the consequences of uncontrolled synovial proliferation. Despite proper medical therapy, joint destruction often results and surgical treatment of the joint deformities may be required for restoration of function. | |
| 7788337 | Bone tissue in rheumatoid arthritis (1). Bone mineral density and fracture risk. | 1995 Mar | Rheumatoid arthritis is associated with locoregional decalcification, which can be clearly demonstrated at the distal radius using single-photon absorptiometry. Bone loss at this site is probably due to the predominant involvement of the hands and wrists during rheumatoid arthritis. Estimates of the frequency of generalized bone loss have varied with the measurement technique used and the study design. Studies using dual-photon absorptiometry with a radioactive source have yielded conflicting data. The most recent studies of bone mineral density used dual energy X-ray absorptiometry, which is currently the best method in terms of reproducibility and precision; results suggested bone loss in the proximal femur, whereas lumbar spine measurements were usually normal or very slightly decreased. Findings from the few longitudinal studies are discordant; this may be ascribable to differences in bone mass measurement techniques, study population characteristics, and follow-up duration. Whereas bone loss was not demonstrated in the earliest longitudinal studies, recent investigations suggested that bone mineral density was decreased in rheumatoid arthritis patients as compared with controls. Corticosteroid therapy, even in daily dosages of less than 10 mg/d prednisone-equivalent, was associated with an approximately 10% decrease in bone mass after six months, in both cross-sectional and longitudinal studies. Rheumatoid arthritis patients had a two-fold increase in fracture risk, independently from their bone mass. Factors associated with higher fracture risks were corticosteroid therapy, physical inactivity, and female gender. | |
| 1575593 | Infectious arthritis in patients with rheumatoid arthritis. | 1992 Mar | Eleven cases of infectious arthritis occurring in patients with rheumatoid arthritis are reported. Staphylococcus aureus was the causative organism in eight patients. Streptococcus anginosus and Streptococcus agalactiae in one patient each, and Mycobacterium tuberculosis in two patients. The mean duration of symptoms before diagnosis was 16 days in patients with pyogenic arthritis. The diagnosis of joint infection caused by Mycobacterium tuberculosis was especially delayed (57 days). Four patients died; they were found to have a longer time to diagnosis and two of them had multiple joint infection. Although Staphylococcus aureus is the microorganism most often affecting patients with rheumatoid arthritis, infection caused by Mycobacterium tuberculosis must also be considered in such patients. |