Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
10930126 Characteristics of polyarthritis in rabbits by hyperimmunization with attenuated Enterococ 2000 Jun To produce polyarthritis and rheumatoid factor like substance (RFLS), rabbits were hyperimmunized intravenously with 0.02% thimelosal (TMS)-treated Enterococcus faecalis (E. faecalis) as a persistent bacterial flora. Swelling of knee joints occurred at a rate of 41% (27/66), and of shoulder joints at a rate of 25% (17/66) while that of elbow joints occurred at a rate of 4.5% (3/66). On culturing of knee joint fluids, no colonies appeared while 2/4 fluid specimens from the shoulder joints gave positive colonies for 78 days after the first immunization; thereafter, no colonies appeared. On histological examination, in early stages, acute inflammatory reactions with degenerative changes of synovial tissue was observed. In later stages, chronic inflammatory changes, proliferation of synovial cells with pannus formation, destruction of articular cartilage and subchondral bone were observed. RFLS titer showed bi-phasic peaks at 11 days and 41 days after the first immunization. A high incidence of polyarthritis, particularly knee joints, occurred. Thus, hyperimmunization with attenuated E. faecalis as a normal intestinal flora may provide an animal model of chronic polyarthritis.
9263152 Amelioration of type II collagen induced arthritis in rats by treatment with thymulin. 1997 Aug OBJECTIVE: To investigate the effects of thymulin (serum thymic factor + Zn2+) in collagen induced arthritis (CIA) in rats. METHODS: SD rats were immunized with bovine type II collagen plus Freund's incomplete adjuvant, and thymulin was administered intraperitoneally on the first day of first immunization. We determined the level of serum thymulin by rosette inhibition assay. Effects of thymulin on CIA rats were estimated by measuring the extent of hind paw edema, the level of serum anti-type II collagen antibody, and changes in histopathological features of the affected joints. RESULTS: Serum thymulin levels in CIA rats were significantly lower than in untreated rats. Thymulin diminished hind paw swelling and onset of arthritis compared with control rats. The serum anti-type II collagen antibody level was also reduced by thymulin. Histopathological examination showed inhibition of granulation tissue and new bone formation after injection of thymulin. CONCLUSION: Our results suggest thymulin plays a significant role in the onset and development of CIA in rats. Our data indicate thymulin may be therapeutically effective in preventing the development of rheumatoid arthritis.
10211891 Quantifying the exact role of HLA-DRB1 alleles in susceptibility to inflammatory polyarthr 1999 Apr OBJECTIVE: To accurately determine the contributions of HLA-DRB1 alleles in explaining susceptibility to inflammatory polyarthritis in a large, true population-based cohort of new-onset cases. METHODS: A cohort of 680 consecutive patients with inflammatory polyarthritis, of whom 404 satisfied the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), was recruited from the population-based Norfolk Arthritis Register. All cases were compared with 286 local population controls. A standardized clinical assessment was performed on all patients. HLA-DRB1 phenotypes, including DR4 subtypes, were determined using a semiautomated, reverse dot-blot method. Results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: There was only a modest association (OR 1.8, 95% CI 1.4-2.4) between inflammatory polyarthritis and the presence of any shared epitope (SE) allele; the strongest individual risk was with DRB1*0404 (OR 3.5, 95% CI 1.8-6.8). Comparison of the genotypes demonstrated that the effect of being SE homozygous (OR 2.1, 95% CI 1.5-3.0) was only moderately greater than the effect of being SE heterozygous (OR 1.3, 95% CI 1.1-1.6). The exception to this was genotypic combinations that included HLA-DRB1*0404, which exhibited ORs ranging up to 18.0. There were no differences between either the phenotype or genotype data when the patients were stratified by RA status (defined by the ACR criteria). In contrast, the associations were substantially stronger in patients who were positive for rheumatoid factor. CONCLUSION: Previous studies had not been able to clarify whether the influence of HLA-DRB1 on RA was related to disease susceptibility or to disease severity and progression. These data on a unique population-based incident cohort suggest only weak effects on susceptibility, with the exception of the clearly distinct influence of HLA-DRB1*0404.
9510154 Induction of autoimmune arthritis in HLA-DR4 (DRB1*0401) transgenic mice by immunization w 1998 Mar 15 Although associations between the expression of particular HLA genes and the susceptibility to specific autoimmune diseases has been known for some time, the role that these HLA molecules play in the autoimmune response is unclear. Through the establishment of a chimeric HLA-DR/I-E transgene, we have examined the function of the rheumatoid arthritis (RA) susceptibility allele HLA-DR4 (DRB1*0401) in presenting antigenic peptides derived from the model Ag, type II collagen (CII), and in mediating an autoimmune response. As a transgene, the chimeric DR4 molecule conferred susceptibility to an autoimmune arthritis induced by immunization with human CII or bovine CII. These mice developed an inflammatory, autoimmune arthritis that was similar both histologically and in severity to that previously described for the collagen-induced arthritis model. The DR4-mediated autoimmune arthritis was accompanied by T cell and B cell responses to both the immunogen and the autoantigen, murine CII. The DR4-restricted T cell response to human CII was focused on an immunodominant determinant within CII263-270 and a minor determinant within CII286-300, the same CII determinants recently identified for yet another RA susceptibility allele, HLA-DR1 (DRB1*0101). Thus these data demonstrate that, like HLA-DR1, HLA-DR4 is capable of binding peptides derived from human CII and therefore probably plays a role in the autoimmune response to human CII observed in RA patients.
17657445 Perceptual variation in categorizing individual peripheral joints for the presence or abse 1999 The clinical diagnosis of osteoarthritis in the peripheral skeleton is dependent on the skilled examination of several features characteristic of the condition. However, we have previously observed that even highly experienced rheumatologists in Australia and Canada may not completely agree on the clinical examination in individuals with osteoarthritis (OA), rheumatoid arthritis, ankylosing spondylitis, fibromyalgia, scleroderma and painful shoulder.
11004950 [Pharmacotherapeutic compass 2000/2001]. 2000 Sep 9 The Commission Pharmaceutical Help of the Health Care Insurance Board uses the Pharmacotherapeutical compass to inform the medical profession annually about medical drugs. In the 2000/2001 edition the most important alterations are changes in the introductions of: antidepressants, medicines for peptic disorders, medicines for rheumatoid arthritis and osteoarthritis, haematopoietic growth factors, anticonvulsants, medicines for Parkinson, medicines for congestive heart failure, antiretroviral medicines, medicines for osteoporosis, short acting insuline-analogues and oral antihyperglycaemics. The introductions about Horton's neuralgia and erectile dysfunction are new. For some (new) medicines recommendations are made, for the antidepressants and medicines for peptic disorders some recommendations have been changed.
11083283 Unmethylated oligo-DNA containing CpG motifs aggravates collagen-induced arthritis in mice 2000 Nov OBJECTIVE: To investigate the effects of an intradermal injection of an unmethylated oligodeoxynucleotide (ODN) containing CpG motifs on the severity of collagen-induced arthritis (CIA). METHODS: CIA was induced in DBA/1 LacJ mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant followed 3 weeks later by immunization with CII in Freund's incomplete adjuvant (yielding CIA mice). Unmethylated ODN containing a CpG motif was injected intradermally into DBA/1 LacJ mice at a dosage of 20 microg (yielding CpG-CIA mice) 1 week prior to the first immunization with CII. Unmethylated ODN containing a GpC motif instead of a CpG motif and ODN containing a methylated CpG motif were used to produce controls (GpC-CIA mice and mCpG-CIA mice, respectively). After the second immunization with CII, arthritis scores were measured weekly up to the eighth week. At the eighth week, the mice were killed, histopathologic changes in the ankle joints were examined, and titers of interferon-gamma (IFNgamma) in the supernatants of splenocytes (1 x 10(7)) stimulated in culture by CII for 3 days were determined by enzyme-linked immunosorbent assay. RESULTS: CpG-CIA mice had significantly higher arthritis scores than CIA mice. CpG-CIA mice had more severe histopathologic changes than CIA mice and mCpG-CIA mice. Moreover, splenocytes in CpG-CIA mice produced higher IFNgamma titers in response to CII than did splenocytes in CIA mice and mCpG-CIA mice. CONCLUSION: Injection of unmethylated oligo-DNA containing CpG motifs aggravated CIA through activation of the Th1-type immune response, suggesting that microbial infection could be one of the mechanisms for aggravation or exacerbation of arthritis or, alternatively, that such infection could be an adjuvant in the induction of arthritis in rheumatoid arthritis.
10381034 Effects of interleukin 1 receptor antagonist alone and in combination with methotrexate in 1999 Jun OBJECTIVE: To determine the benefit of combination treatment with the interleukin 1 receptor antagonist (IL-1ra) and methotrexate (MTX) in adjuvant arthritic rats. METHODS: Rats with adjuvant arthritis were treated by continuous sc infusion with IL-1ra (5 mg/kg/h). Effects of IL-1ra treatment alone were compared to treatment with daily oral MTX (0.048, 0.06, or 0.075 mg/kg) or MTX in combination with IL-1ra. Efficacy was monitored by sequential caliper measurement of ankle joints, final paw weights, and histologic evaluation with particular emphasis on bone lesions. RESULTS: Treatment with IL-1ra alone resulted in 6% inhibition of paw swelling assessed by final paw weight. Treatment with MTX (0.075 mg/kg PO) gave 47% inhibition and the combination resulted in an 84% decrease in swelling. Histologic evaluation of ankle joints revealed 53% inhibition of bone resorption with IL-1ra alone, 58% inhibition with MTX alone, and 97% inhibition in combination treated rats. Lower doses of MTX in combination with IL-1ra also provided additive benefit on arthritis variables. CONCLUSION: Combination therapy with IL-1ra and MTX results in additive or synergistic benefit, with excellent inhibition of all arthritis variables. These data support clinical investigation of the use of combination therapy of IL-1ra and MTX in patients with rheumatoid arthritis.
9631748 Matrix metalloproteinases, IL-6, and nitric oxide in rat antigen-induced arthritis. 1998 May OBJECTIVE: Degradation of extracellular matrix by matrix metalloproteinases (MMPs) is believed to be important in processes leading to the progressive destruction of joints in rheumatoid arthritis (RA). We used the model of antigen-induced arthritis (AIA) to study MMP activity and the influence of cytokines on their expression by synoviocytes. MATERIAL AND METHODS: Procedures used were: mBSA-induced arthritis in rats; investigation of synovial fluids and supernatants of cultured synoviocytes at different time points during AIA; estimation of total MMP activities by fluorescence assay; zymographic investigations; IL-6 bioassay with B9 cells; nitric oxide (NO) estimation. RESULTS: Total MMP activity in the synovial fluids of arthritic joints was higher than in the contralateral joints or in the joints of untreated control animals. The maximum was noted between day 7 and day 14 after arthritis induction. Cultured synoviocytes, prepared at different time points after arthritis induction, secreted MMPs into the media with a maximum time lapse of 14 days after arthritis induction. TNF-alpha increased the total MMP activity released. Moreover, TNF-alpha as well as IL-1 beta induced the expression of MMP9. Finally, TNF-alpha increased the levels of IL-6 and NO in the supernatants of synoviocytes; the extent of stimulation was dependent on the course of AIA. CONCLUSIONS: Different MMPs are synthesized in varying concentrations during the course of rat AIA. Cytokines such as TNF-alpha and IL-1 beta differentially influence the activity and expression of MMPs in cultured synoviocytes. The participation of MMPs in tissue degradation during the course of arthritis may be of importance for the development of new therapeutic strategies.
9605172 Soluble IL-15 receptor alpha-chain administration prevents murine collagen-induced arthrit 1998 Jun 1 IL-15 has recently been detected in the synovium of patients with rheumatoid arthritis. IL-15-activated T cells induce significant TNF-alpha synthesis by macrophages via a cell contact-dependent mechanism, suggesting a key regulatory role for IL-15. Here, we report that the administration of a soluble fragment of IL-15Ralpha into DBA/1 mice, profoundly suppressed the development of collagen-induced arthritis. This was accompanied in vitro by marked reductions in Ag-specific proliferation and IFN-gamma synthesis by spleen cells from treated mice compared with control mice and in vivo by a significant reduction in serum anti-collagen Ab levels. These data directly demonstrate a pivotal role for IL-15 in the development of inflammatory arthritis and also suggest that antagonists to IL-15 may have therapeutic potential in rheumatic diseases.
11379486 Polymyalgia rheumatica--an underdiagnosed disease. 2000 Characteristic features of polymyalgia rheumatica, a widely underdiagnosed disease, are described. The features of the disease are illustrated by the authors' own experience in the treated patients, and compared with literature data. According to the authors' experience, patients with polymyalgia rheumatica are mostly treated for inaccurate diagnoses such as cervicobrachial or lumbosacral syndrome, seronegative rheumatoid arthritis, unexplained febrile state, or precipitated erythrocyte sedimentation rate of unknown etiology. This results is delayed diagnosis or the accurate diagnosis is never reached at all.
20086811 Foot problems in middle-aged patients: keeping active people up to speed. 1998 May Most of the common foot problems that bother active middle-aged people are self-limiting and easily treated if detected early. Reviewed here are the causes, symptoms, diagnosis, and treatment of hallux valgus and rigidus, lesser-toe deformities, corns, Morton's neuroma, metatarsal stress fractures, plantar fasciitis, posterior tibialis tenosynovitis and rupture, acquired pes planus, tarsal tunnel syndrome, and foot problems related to rheumatoid arthritis and diabetes. In most cases, conservative treatment will enable patients to return to activity relatively quickly.
9463396 Interleukin 6 is required for the development of collagen-induced arthritis. 1998 Feb 16 Interleukin-6 (IL-6) is overproduced in the joints of patients with rheumatoid arthritis (RA) and, based on its multiple stimulatory effects on cells of the immune system and on vascular endothelia, osteoclasts, and synovial fibroblasts, is believed to participate in the development and clinical manifestations of this disease. In this study we have analysed the effect of ablating cytokine production in two mouse models of arthritis: collagen-induced arthritis (CIA) in DBA/1J mice and the inflammatory polyarthritis of tumor necrosis factor alpha (TNF-alpha) transgenic mice. IL-6 was ablated by intercrossing an IL-6 null mutation into both arthritis-susceptible genetic backgrounds and disease development was monitored by measuring clinical, histological, and biochemical parameters. Two opposite responses were observed; while arthritis in TNF-alpha transgenic mice was not affected by inactivation of the IL-6 gene, DBA/1J, IL-6(-/-) mice were completely protected from CIA, accompanied by a reduced antibody response to type II collagen and the absence of inflammatory cells and tissue damage in knee joints. These results are discussed in the light of the present knowledge of cytokine networks in chronic inflammatory disorders and suggest that IL-6 receptor antagonists might be beneficial for the treatment of RA.
11268332 Autologous bone marrow transplantation versus alternative drugs in pediatric rheumatic dis 2000 Nov A minority of children suffering from severe rheumatic diseases are unresponsive to conventional treatments. These patients can now be managed with a variety of immunosuppressive therapies. Methotrexate is considered the first choice disease-modifying agent for adult and juvenile rheumatoid arthritis. In patients unresponsive to low doses of methotrexate, medium or high-doses can be useful. Instead of methotrexate, a recently developed immunosuppressive drug, mycophenolate-mofetil, which inhibits T- and B-lymphocyte proliferation, can be used. Another possibility for refractory rheumatic diseases, with no increase in toxicity, is combination therapy, for example methotrexate plus cyclosporine, or methotrexate plus salazopyrine or intravenous pulses of cyclophosphamide and methylprednisone. More recently two distinct inhibitors of tumor necrosis factor (etanercept and infliximab have been used successfully for intractable rheumatic diseases (juvenile idiopathic arthritis, psoriatic arthritis, spondyloarthropathies) but the follow-up is still too short to establish their long-term effectiveness. If all these treatments are unsuccessful, an autologous bone marrow transplantation can be proposed to selected patients. Interesting results have been obtained in pediatric rheumatic diseases such as juvenile idiopathic arthritis, systemic lupus erythematosus and systemic sclerosis. Further studies are required to assess the best procedures able to induce remission with a minimal risk of fatal events.
10088781 Interferon-beta1A-induced polyarthritis in a patient with the HLA-DRB1*0404 allele. 1999 Mar Human interferon-alpha (IFNalpha) and IFNbeta are administered for treatment of several diseases, including viral infections, malignancies, and multiple sclerosis (MS). IFNalpha therapy has been associated with the production of autoantibodies and the development of a variety of autoimmune disorders, including polyarthritis. This report describes the development of seronegative, symmetric polyarthritis in a patient with relapsing-remitting MS, after 8 weeks of therapy with IFNbeta1a. HLA phenotyping analysis of the patient revealed the presence of HLA-DRB1*0404, an allele known to be associated with the development of rheumatoid arthritis. Therefore, IFNbeta1a may have induced arthritis in a patient who was genetically predisposed to develop arthritis on the basis of HLA determinants. The English-language literature regarding IFNalpha- and IFNbeta-induced polyarthritis is reviewed, and possible mechanisms for IFNalpha- and IFNbeta-induced autoimmunity, including the contribution of HLA determinants and nitric oxide overproduction, are discussed.
15775463 [Factors inducing severe osteoporosis]. 2001 Dec Among various factors advancing bone loss, immobility is the most remarkable cause to deteriorate osteoporosis. In the animal experiment, we could be obvious that immobilization of femur by suspension of rat tail reduced calcium content of bone through diminished blood circulation of bone, especially in femoral neck. In stroke patients who are often suffered from femoral neck fracture, bone mineral measurement revealed bone loss in paralyzed limb, in addition to healthy limb. Bone loss in both limbs in the hemiplegic patient and the fragility of femoral neck are caused by decrease of daily activity. Low nutrition in the patients who are took gastrectomy and suffered from rheumatoid arthritis is pointed out as the other factor inducing severe osteoporosis.
10196431 Knee: role and results of allografts. 1999 Apr The vast majority of periprosthetic fractures occur as the result of trauma. There are many predisposing factors for these factors, including osteopenia, neurologic disorders, medications, rheumatoid arthritis, previous arthroplasty, and infection. These same factors also increase the likelihood of fracture comminution, and the presence of poor bone quality makes fixation difficult and prone to failure.
10079585 Carpal tunnel syndrome: the cause dictates the treatment. 1999 Mar Mild carpal tunnel syndrome should be conservatively treated and severe carpal tunnel syndrome usually requires surgery; however, management of moderate carpal tunnel syndrome is more complex. Usually, the treatment is dictated by the cause, which may be occupational injury, acute trauma, systemic diseases such as diabetes, hypothyroidism, or rheumatoid arthritis, or other causes.
10680195 Photopheresis and autoimmune diseases. 2000 Feb Although several case reports and case series suggest efficacy for photopheresis in the treatment of autoimmune diseases, few controlled studies have been conducted to test this hypothesis. After a decade of interest, multiple case reports, open trials, and one controlled study, the role of photopheresis in autoimmune disease remains to be established. Controlled multi-center trials in rheumatoid arthritis, SLE, and scleroderma may be costly but are clearly necessary for proper evaluation of this therapy.
9756971 Cervical deformity: rationale for selecting the appropriate fusion technique (anterior, po 1998 Oct This article examines cervical deformities and their treatments, such as iatrogenic deformities, posttraumatic deformities, ankylosing spondylitis, rheumatoid arthritis, degenerative subaxial spondylolisthesis, myopathy, infectious spondylitis, and tumors. Congenital scoliosis and kyphosis and torticollis and rotatory atlanto-axial subluxation also are discussed.