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Objectives. To analyse the association of autoantibodies against cardiolipin (CL) and oxidized low density lipoproteins [copper-oxidized low density lipoprotein (oxLDL), malondialdehyde-modified LDL (MDA-LDL)] with rheumatoid arthritis (RA) and cardiovascular complications. Methods. One hundred and twenty-one patients with RA were consecutively included. Autoantibodies were determined by ELISA. Healthy individuals from the same region were used as controls. Results. Levels of IgG, IgM and IgA antibodies against MDA-LDL and CL, as well as IgG and IgA antibodies against oxLDL were increased in the patients (P

Certain alleles of cytokine genes interleukin-1 beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor alpha (TNF-alpha) are correlated with increased production of the proteins. The aim of this study was to investigate polymorphisms of these genes and their possible correlation with the development of stroke. This matched case-control study was nested within the population-based Västerbotten Intervention Program (VIP) cohort and the Northern Sweden World Health Organization MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases) cohort, based on individuals who were free from cardiovascular events when the cohorts were established. After an average period of 34.1 months, 113 individuals developed stroke and to each case 2 individuals not suffering from cardiovascular events were matched to serve as controls. Polymerase chain reaction amplification was used to analyze genetic polymorphisms. There was no association between polymorphic sites of the IL-1beta and IL-1Ra genes and stroke. Carriage of haplotype A2+IL-1beta/A2+IL-1Ra was significantly increased in normotensive cases (23.1%) compared with normotensive controls (8.9%) (odds ratio [OR] = 3.07; P = .045). In hypertensive male cases, there was an association between the A1A1 genotype of TNF-alpha and risk of stroke (OR = 2.46; P = .034). Our findings indicate an association between allele A1 of the TNF-alpha NcoI polymorphism and stroke in hypertensive male cases, as well as an association between haplotype A2+IL-1beta/A2+IL-1Ra and stroke in normotensive cases.

To measure markers of atherogenesis and thrombogenesis in patients with rheumatoid arthritis (RA) and in matched controls, and to relate these variables to markers of inflammation and endothelial activation, and to the presence of atherosclerosis.Thirty-nine patients with RA with disease onset between 1974 and 1978, who were younger than 65 years at the present study in 1997, were investigated together with 39 age and sex matched controls. IgG, IgA, and IgM antibodies against oxidized low density lipoprotein (oxLDL ab), malondialdehyde LDL (MDA-LDL ab) and cardiolipin (aCL) were measured by ELISA, circulating immune complexes (CIC) were isolated by precipitation, and homocysteine was measured with HPLC. Hemostatic factors of endothelial origin, i.e., plasminogen activator inhibitor-1 (PAI-1 mass), von Willebrand Factor (vWF), and D-dimer were analyzed by ELISA, and tissue plasminogen activator (tPA) activity was analyzed by a chromogen method. The products analyzed in the RA group correlated with soluble adhesion molecules (sICAM-1, sE-selectin), acute phase reactants, interleukin 6 (IL-6), and IL-2sR alpha, all measured by ELISA, and with accumulated disease activity. The factors were also related to the presence of plaque measured by duplex scanning. Factor analysis was performed to subgroup data in order to find latent variables.Patients with RA had significantly higher levels of oxLDL ab (IgM), MDA-LDL ab (IgA, IgM classes), aCL (IgG, IgA, IgM classes), CIC, homocysteine, PAI-1 mass, and D-dimer than controls. Patients also had significantly higher levels of sICAM-1, sE-selectin, IL-6, and IL-2sR alpha. PAI-1 mass, D-dimer, vWF, CIC, and aCL (IgM, IgA) correlated with erythrocyte sedimentation rate (ESR), and, with the exception of vWF, to accumulated disease activity. CIC correlated significantly with IgM antibodies against oxLDL and aCL. ESR, IL-2sR alpha, PAI-1, tPA activity, vWF, D-dimer, homocysteine, aCL (IgA), and MDA-LDL ab (IgA) correlated with sICAM-1. ESR, haptoglobin, IL-2sR alpha, PAI-1 mass, D-dimer, aCL (IgM), and MDA-LDL ab (IgM) correlated with sE-selectin. sICAM-1 was significantly higher in patients with plaque. In factor analysis, presence of atherosclerotic plaque had loadings of one latent variable together with adhesion molecules and IL-2sR alpha and together with antibodies of, in particular, IgM type of another one.Several different etiopathogenic mechanisms for increased cardiovascular mortality in RA are implicated. Continuous endothelial activation is suggested by increased levels of adhesion molecules sICAM-1 and sE-selectin, which correlate with hemostatic factors of endothelial origin and with T cell activation as measured by IL2sR alpha. That factor analysis showed loadings of one variable on antilipid antibodies and plaque and another on T cell activation and plaque indicates that the immune system is involved in the development of atherosclerosis in RA.

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.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-I 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.The allele A1 of TNF-alpha was more common in the patient group (p0.01; 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 (p0.05), had a higher accumulated disease activity (p0.05) and worse functional class (p0.05). Patients with genotype A2A2 of IL- 1beta had higher accumulated disease activity score than patients with A1A1 and A1A2 (p0.05). The allelic combination Al IL-1beta/A2 IL-1Ra was less prevalent in RA patients who developed cardiovascular complications (p0.005; OR = 0.20).The Al 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 A1IL-1beta/A2 IL-1Ra is less often present in RA patients who developed cardiovascular complications.