Re-examination of histocompatibility antigens found in patients with juvenile rheumatoid arthritis.

One hundred and twenty-three patients with juvenile rheumatoid arthritis and a similar number of controls were tissue typed for 30 HL-A antigens to determine if there were any associations between particular HL-A antigens and the disease. None were found. However, HL-A7 was found more frequently in patients with juvenile rheumatoid arthritis demonstrating tenosynovitis than in the population with juvenile rheumatoid arthritis as a whole. These observations fail to support the contention of others that HL-A-W27 is found more frequently than expected in such patients.     

Spotlight on etanercept in rheumatoid arthritis,psoriatic arthritis and juvenile rheumatoid arthritis

Etanercept (Enbrel) is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-alpha, a proinflammatory cytokine. In patients with early active rheumatoid arthritis, etanercept 25mg twice weekly was associated with a more rapid improvement in disease activity and a significantly greater cumulative response than methotrexate over 12 months of treatment in a randomised, double-blind trial. In addition, etanercept recipients showed a slower rate of radiographic progression and a more rapid improvement in quality of life than methotrexate recipients. The efficacy of etanercept was maintained at 3 years' follow-up. Etanercept was also significantly better than placebo at reducing disease activity in patients who had an inadequate response to previous treatment with disease-modifying antirheumatic drugs (DMARDs) in several well controlled trials. At study end (after 3 or 6 months' treatment), the percentage of patients achieving an American College of Rheumatology 20% (ACR20) response with etanercept (25mg or 16 mg/m(2) twice weekly) was 59-75% as monotherapy and 71% in combination with methotrexate; corresponding placebo response rates were 11-14% and 27%, respectively. Response has been maintained in patients who continued treatment for up to 5 years. In patients with psoriatic arthritis, etanercept 25mg twice weekly significantly reduced disease activity and improved skin lesions in two double-blind, placebo-controlled, 12- to 24-week trials. In the 24-week study, ACR20 response rates (50 vs 13%), psoriatic arthritis response rates (70 vs 23%) and the median improvement in skin lesions (33 vs 0%) were significantly greater in etanercept than in placebo recipients. In patients with polyarticular-course juvenile rheumatoid arthritis, etanercept resulted in improvements in all measures of disease activity and was significantly more effective than placebo at reducing disease flare. Eighty percent of patients receiving etanercept achieved a > or =30% reduction in disease activity over 7 months of treatment, and this was maintained for up to 2 years in a trial extension. Etanercept was generally well tolerated in children and adults in clinical trials; the most commonly occurring adverse effects included injection site reactions, infection, headache, rhinitis and dizziness. In conclusion, etanercept has emerged as an important new treatment option in inflammatory arthritis. Etanercept provides rapid and sustained improvements in disease activity in patients with early and DMARD-refractory rheumatoid arthritis and has been shown to inhibit radiographic progression in those with early disease. Well controlled studies have also demonstrated the efficacy of etanercept in patients with psoriatic arthritis or polyarticular-course juvenile rheumatoid arthritis.     

Etanercept therapy in children with juvenile rheumatoid arthritis.

Etanercept is an effective inhibitor of tumor necrosis factor that has shown a beneficial effect in patients with juvenile rheumatoid arthritis (JRA) that did not respond to other disease-modifying drugs. Here we report 3 patients with JRA who were refractory to traditional therapy; 1 with systemic JRA and 2 with polyarticular JRA. They received etanercept 0.4 mg/kg (maximum 25 mg) subcutaneously, twice a week for 3 months. The symptoms of arthritis improved significantly except that the patient with systemic JRA had disease flare-up during etanercept therapy. Two patients had upper respiratory tract infection during etanercept therapy and 1 suffered from seizure attack. The 2 patients with polyarticular JRA had disease flare-up within 2 months after etanercept was discontinued. This is the first report of etanercept treatment in JRA patients in Taiwan.     

Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis.

Focal resorption of bone at the bone-pannus interface is common in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and can result in significant morbidity. However, the specific cellular and hormonal mechanisms involved in this process are not well established. We examined tissue sections from areas of bone erosion in patients with RA and JRA. Multinucleated cells (MNCs) were present in resorption lacunae in areas of calcified cartilage and in subchondral bone immediately adjacent to calcified cartilage, as previously described. mRNA for the calcitonin receptor (CTR) was localized to these MNCs in bone resorption lacunae, a finding that definitively identifies these cells as osteoclasts. These MNCs were also positive for tartrate-resistant acid phosphatase (TRAP) mRNA and TRAP enzymatic activity. Occasional mononuclear cells on the bone surface were also CTR positive. Mononuclear cells and MNCs not on bone surfaces were CTR negative. The restriction of CTR-positive cells to the surface of mineralized tissues suggests that bone and/or calcified cartilage provide signals that are critical for the differentiation of hematopoietic osteoclast precursors to fully differentiated osteoclasts. Some MNCs and mononuclear cells off bone and within invading tissues were TRAP positive. These cells likely represent the precursors of the CTR-TRAP-positive cells on bone. Parathyroid hormone receptor mRNA was present in cells with the phenotypic appearance of osteoblasts, in close proximity to MNCs, and in occasional cells within pannus tissue, but not in the MNCs in bone resorption lacunae. These findings demonstrate that osteoclasts within the rheumatoid lesion do not express parathyroid hormone receptor. In conclusion, the resorbing cells in RA exhibit a definitive osteoclastic phenotype, suggesting that pharmacological agents that inhibit osteoclast recruitment or activity are rational targets for blocking focal bone erosion in patients with RA and JRA.     

Autoantibodies to DNA topoisomerase II in juvenile rheumatoid arthritis.

Sera from 58 children with juvenile rheumatoid arthritis were examined for the presence of antibodies to DNA topoisomerase II. Eight sera were reactive in immunoblotting with purified human topoisomerase II and a protein encoded by a cloned cDNA expressed in Escherichia coli which represents the carboxy-terminal domain of the human enzyme. In addition, the sera detect topoisomerase II in mitotic chromosomes and chromosome scaffolds. Five of the sera bind to the native enzyme in solution and deplete such solutions of the active enzyme. All eight sera also contain antibodies to nuclear antigens other than topoisomerase II.     

HLA-DR antigens in rheumatoid arthritis in North India

A study of 40 patients of classical or definite rheumatoid arthritis of North India origin diagnosed on ARA criteria revealed a significant increase in the frequency of HLA-DR4 (70%) as compared to the control population (1 2.5%) giving a relative risk of 16.33. Thus, in the native North Indian population, the genes for susceptibility to RA seem to be in linkage disequilibrium with the same DR determinant as in the white Caucasoid population.     

HLA antigens in Tlingit Indians with rheumatoid arthritis

HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns).     

Abrupt temperature change triggers arthralgia in patients with juvenile rheumatoid arthritis.

BACKGROUND AND PURPOSE: Juvenile rheumatoid arthritis (JRA) is the most common form of arthritis in children and affects both quality of life and school attendance. Weather and temperature conditions are believed to affect joint pains; however, very few studies have investigated this issue. This study examined the association between joint pain in JRA patients and weather conditions. METHODS: The daily pain ratings of 52 patients previously diagnosed with JRA were recorded on visual analog scales over 4 months beginning January 1, 2004. These ratings were then compared with weather data to evaluate possible correlation between these two factors. RESULTS: Twenty nine patients kept daily records during the first 2 months. There was no positive correlation between weather parameters (such as temperature, humidity, and barometric pressure) and pain ratings. Interestingly, the pain rating significantly increased the day after the advent of a cold wave (sign test, p<0.01; Wilcoxon signed ranks test, p=0.001). The number of patients who experienced joint swelling was not related to weather conditions. Twenty one participants continued maintaining the diaries during the next 2 months. The patients reported higher pain levels in the first 2 months during the cold wave period than in the next 2 months when the cold wave period had ended (p<0.001). CONCLUSION: A dramatic weather change such as a sudden cold wave might influence the experience of joint pain.