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- Cvetkovic, Jasmina Trifunovic, et al.
(författare)
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Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1 beta, and IL-lRa genes
- 2002
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 29:2, s. 212-219
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To analyze the association of genetic polymorphisms of pro-inflammatory cytokines with rheumatoid arthritis (RA) in comparison with healthy controls from Northern Sweden and the potential contribution of these genetic variants for disease severity and development of cardiovascular complications. Methods. Polymerase chain reaction amplification was used for analysis of TaqI restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1beta), variable tandem repeat polymorphism of IL-1 receptor antagonist (IL-1Ra) gene and NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-alpha) gene, One hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively recruited into the study through the Department of Rheumatology. Results. The allele A1 of TNF-alpha was more common in the patient group (p < 0.01 OR = 1.62). Patients having the genotype A1A2 seemed to develop more severe disease compared with patients with A1A1 genotype: they were younger at disease onset (p < 0.05), had a higher accumulated disease activity (p < 0.05) and worse functional class (p < 0.05), Patients with genotype A2A2 of IL-1beta had higher accumulated disease activity score than patients with A1A1 and A1A2 (p < 0.05). The allelic combination A1 IL-1beta/A2 IL-1Ra was less prevalent in RA patients who developed cardiovascular complications (p < 0.005 OR = 0.20). Conclusions. The A1 allele of TNF-alpha associates with RA. Genotypes A1A2 of TNF-alpha and A2A2 of IL-1beta are associated with more severe disease. The allelic combination A1 IL-1beta/A2 IL-1Ra is less often present in RA patients who developed cardiovascular complications.
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| 2. |
- Westermark, T, et al.
(författare)
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Increased content of bombesin/GRP in human synovial fluid in early arthritis : different pattern compared with substance P
- 2001
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 19:6, s. 715-720
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Tidskriftsartikel (refereegranskat)abstract
- Objective Bombesin (BN) and the mammalian homologue gastrin-releasing peptide (GRP) are known trophic factors, neurotransmitters and paracrine hormones. BN/GRP has not previously been demonstrated in synovial fluid. In this study, the amounts of BN/GRP and substance P (SP) present in synovial fluid from the knee joints of patients with rheumatoid arthritis (RA) and of healthy, controls were measured. Methods Synovial fluid from the knee joint was collected from patients with either longstanding RA (n = 32) or early arthritis (symptoms for < 12 months; n = 9) and from control subjects, i.e., individuals without known joint disease (n = 10). These samples were analyzed using radioimmunoassays. Results Levels of BN/GRP-like peptide were below the assay detection limits in synovial fluid from controls. Detectable levels of immunoreactive BN/GRP were present in the majority of patients with either longstanding RA or early arthritis. The levels were significantly higher in the synovial fluid from patients classified as having early, arthritis compared with those with longstanding RA (p < 0.05). There was a strong correlation between BN/GRP levels and the number of leukocytes in the synovial fluid in the patients with early arthritis. The levels of SP-like peptide in the patients, whether with early arthritis or longstanding RA, were significantly elevated compared with controls. However there was no difference in the levels between these two patient groups. Conclusions These observations show that BN/GRP-like peptide is present in the synovial fluid of joints affected by arthritis and that the pattern of BN/GRP increase differs from that of SP It appears as if the presence of BN/GRP is particularly related to the early processes of joint involvement. These observations are of interest because BN/GRP has well-known trophic and paracrine effects and chondrocytes have recently been shown to produce neuropeptides such as BN/GRP.
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| 3. |
- Wållberg-Jonsson, Solveig, et al.
(författare)
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Hemostatic factors and cardiovascular disease in active rheumatoid arthritis : an 8 year followup study
- 2000
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 27:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the prospective effect of hemostatic factors and inflammatory variables on the progression of cardiovascular disease in rheumatoid arthritis (RA). Methods. Von Willebrand factor (vWF) and the fibrinolytic factors tissue plasminogen activator (tPA), measured as tPA capacity, and plasminogen activator inhibitor 1 (PAI-1), platelets, fibrinogen, and inflammatory markers were measured in 74 patients with active seropositive RA. Lipid levels, lipoprotein(a), and cardiolipin antibodies were also analyzed. Cardiovascular disease, measured by past cardiovascular events including thrombotic events, was registered in an 8 year followup. Results. Patients with a cardiovascular event during the followup period (n = 26) had significantly higher levels of vWF PAI-1, erythrocyte sedimentation rate (ESR), and haptoglobin at entry to the study. In a multiple logistic regression model controlling for several conventional cardiovascular risk factors and pharmacological treatment at sampling, PAI-1 and tPA were significantly associated with cardiovascular disease progression. Conclusion. The altered levels of vWF, PAI-1, and, in logistic regression, tPA in RA patients with cardiovascular disease progression indicates a status of hypofibrinolysis in these patients. Higher levels of ESR and haptoglobin may reflect the importance of the inflammatory process for the development of cardiovascular disease in RA.
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