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- Alenius, Gerd-Marie, et al.
(författare)
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Analysis of 6 genetic loci for disease susceptibility in psoriatic arthritis.
- 2004
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Ingår i: The Journal of rheumatology. - 0315-162X .- 1499-2752. ; 31:11, s. 2230-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the association of several autoimmune disease susceptibility loci in a population of patients with psoriasis and defined joint disease from northern Sweden. METHOD: One hundred twenty patients with psoriasis and defined joint disease were examined clinically, radiologically, and with laboratory-based analyses. Disease classification was based on peripheral and/or axial engagement. The tumor necrosis factor (TNF) locus, 1q21 (PSORS4), 3q21 (PSORS5), 8q24, 16q21, and the CTLA4 gene were analyzed using a total of 38 microsatellite markers and 2 single nucleotide polymorphisms (SNP). Ninety-four controls with the same ethnic background as the patients were randomly selected from the same region of Sweden. RESULTS: An association was found with one of the markers in the TNFB locus within the HLA region (p = 0.012, pc = 0.024). Three markers at the PSORS4 locus on chromosome 1q21 and 2 markers at the 8q24 locus showed nominal p values of < 0.05. After applying the Bonferroni correction for multiple analyses these markers did not reach significance. No other marker showed significant association. In a subgroup of the patients, possible linkage disequilibrium between the TNFB123 and HLA-B antigens, B17, B27, B37, B44, and B62 was analyzed. A significant linkage (p = 0.0001) was found. CONCLUSION: We identified an association between psoriatic arthritis and one of the microsatellite markers within the TNFB locus at the HLA region on chromosome 6. Linkage disequilibrium between TNFB123 and certain HLA-B antigens was found.
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- Alenius, Gerd-Marie, et al.
(författare)
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Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden
- 2002
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 21:5, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.
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- Andersen, Grethe Neumann, et al.
(författare)
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Assessment of vascular function in systemic sclerosis : indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production
- 2002
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 46:5, s. 1324-1332
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc). METHODS: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules. CONCLUSION: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.
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- Andersen, Grethe Neumann, et al.
(författare)
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Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis : findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 1
- 2000
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Ingår i: Arthritis and Rheumatism. - 0004-3591 .- 1529-0131. ; 43:5, s. 1085-1093
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease. Methods We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. Results Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate. Conclusion NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.
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