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Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritisRheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), and are thought to have distinct autoantigen targets. Whilst RF targets the Fc region of antibodies, ACPAs target a far broader spectrum of citrullinated peptides. Here we demonstrate significant sequence and structural homology between proposed RF target epitopes in IgG1 Fc and the ACPA target fibrinogen. Two of the three homologous sequences were susceptible to citrullination, and this modification, which occurs extensively in RA, permitted significant cross-reactivity of RF+ patient sera with fibrinogen in both western blots and ELISAs. Crucially, this reactivity was specific to RF as it was absent in RF− patient and healthy control sera, and could be inhibited by pre-incubation with IgG1 Fc. These studies establish fibrinogen as a common target for both RF and ACPAs, and suggest a new mechanism in RF-mediated autoimmune diseases wherein RF may act as a precursor from which the ACPA response evolves.
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Galectin-2 (LGALS2) 3279C/T polymorphism may be independently associated with diastolic blood pressure in patients with rheumatoid arthritis.The galectin-2 (LGALS2) 3279 C/T single nucleotide polymorphism (SNP) has recently been associated with myocardial infarction (MI). Although hypertension, a very prevalent entity in rheumatoid arthritis (RA), is one of the greatest risk factors for MI, the possible association of LGALS2 3279 C/T and hypertension has not been investigated. We genotyped 386 RA patients, 272 hypertensives and 114 normotensives. Diastolic blood pressure (DBP) was significantly lower in TT compared to CC homozygotes (-4.11 mmHg, p = 0.044) even when adjusted for multiple confounders (-4.28 mmHg, p = 033). Further studies are required to replicate the potential association of LGALS2 3279 C/T with DBP, and examine whether this SNP could be used as a marker of increased risk for future cardiovascular events in RA populations.
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Comparison of the effects of exercise and anti-TNF treatment on cardiovascular health in rheumatoid arthritis: results from two controlled trialsPeople with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Both pharmacological treatment and exercise are suggested in the management of CVD risk in RA. This study explored the effects of exercise and anti-TNF treatment on CVD risk in RA. Twenty RA patients (70% female, 50 (10) years) completed a 3-month exercise intervention and 23 RA patients (65% female, 54 (15) years) started anti-TNF treatment. Markers of disease activity, CVD risk, and vascular function were assessed before and after 3-months of intervention/treatment. Both exercise and anti-TNF treatment improved functional ability and fatigue, anti-TNF treatment was more successful in improving inflammation, disease activity, functional ability and pain. Exercise induced a reduction in overall CVD risk and improvement in vascular function, which was significantly different from anti-TNF treatment where no such changes were found. These findings showed that exercise and anti-TNF had differential effects on CVD risk in RA, and should be combined for optimal CVD risk reduction. Whereas anti-TNF treatment is likely to impact on CVD risk through reducing the systemic inflammatory load, exercise should be recommended to people with RA as an effective self-management strategy to reduce CVD risk further. Once RA patients have responded successfully to anti-TNF treatment, increasing exercise should be encouraged to reduce the risk for CVD. Thus, supporting exercise programmes when the disease is controlled, is likely to enhance the uptake and the maintenance of exercise, which will result in additional benefits to cardiovascular health and wellbeing in people with RA.
