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Metabolism in Patients with Rheumatoid Arthritis: Resting Energy Expenditure, Physical Activity and Diet-Induced Thermogenesis. Invited Review.Metabolism is one of the most important physiological functions. Resting energy expenditure, physical activity and diet are the main factors of total metabolism but the contribution of these components to total energy expenditure may be significantly changed with chronic inflammatory diseases such as rheumatoid arthritis (RA). RA is a disease that alters normal metabolism due to the overproduction of pro-inflammatory cytokines and may lead to rheumatoid cachexia. This review focuses on the individual components of total energy expenditure and discusses how physical activity and diet may influence resting metabolism both in the healthy population as well as patients with RA. Moreover, information is provided regarding the available patents (i.e. equipment and prediction equations) that may be used in order to predict metabolism in the normal population and RA patients.
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Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: The role of obesity and smokingAbstract Background Cardiovascular morbidity and mortality are increased in rheumatoid arthritis (RA). Interleukin-6 (IL-6) is high in RA and, together with smoking and obesity, an important contributor to the development of cardiovascular disease (CVD). The present study examined the potential association of IL-6-174 G/C polymorphism, together with obesity and smoking, with the presence of CVD in RA patients. Methods and results DNA samples were collected from 383 RA patients (who also had extensive clinical and laboratory evaluations). IL-6-174 G/C was identified using real time PCR and melting curve analysis. Serum IL-6 levels were measured in a subgroup of 135 RA patients to examine the functionality of the polymorphism. Carriers of the IL6-174C-allele demonstrated increased prevalence of CVD (26.2% vs. 17.0%, p = 0.041). There was a significant association with CVD, even after adjustment for traditional CVD risk factors (OR = 1.92, 95%CI: 1.03 to 3.58, p = 0.041). IL-6 levels were significantly increased in C-allele carriers [14.02 (3.21–38.81) vs. 4.48 (2.25–16.5), p = 0.028]. No significant interactions were observed between adiposity and IL6-174G/C genotypes. There was only a trend for an interaction between ever smoking and IL6 C-allele carriers on CVD. Conclusion The IL-6-174C-allele may associate with CVD in RA patients and possibly exerts its effect via increased inflammation. This finding, if confirmed in future studies, may be used as a part of a genetic screening tool for RA patients at high CVD risk.
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The Detection and Role of Human Endogenous Retrovirus K (HML-2) In Rheumatoid ArthritisHuman endogenous retroviruses are the remnants of ancient retroviral infections present within our genome. These molecular fossils show similarities with present day exogenous retroviruses but act as typical Mendelian elements that are passed vertically between generations. Despite being repeatedly linked to a number of autoimmune diseases and disorders, no conclusive proof has been identified. Rheumatoid arthritis (RA) is one such disease which has been associated with an increase in HERV expression, compared to controls. In order to elucidate a clear role for HERVs in RA pathogenesis, autoantigens implicated in disease pathogenesis were scanned for sequence homology to retroviral genes. Such epitopes would induce antibodies cross reactive with host proteins, resulting in disease. Short peptides mimicking these regions were synthesised and the prevalence of anti-HERV antibodies was determined in RA patients and disease controls. Additionally, a novel real-time Polymerase Chain Reaction (PCR) assay was developed to accurately quantify levels of HERV-K (HML-2) gag expression, relative to normalised levels of housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) activity in RA patients compared to disease controls with CD4+ lymphocytes harbouring the highest activity. The real-time assay was also used to determine whether factors within the synovium could modulate HERVs, resulting in their upregulation. Exogenous viral protein expression and pro-inflammatory cytokines were shown to exert a significant modulatory effect over HERV-K (HML-2) transcription. From this data, it is clear that RA patients have increased levels of HERV-K (HML-2) gag activity compared to controls. Despite this it is likely that factors within the synovium such as exogenous viral expression and pro-inflammatory cytokines also influence HERV-K (HML-2) transcription possibly contributing to a role of bystander activation, i.e. being influenced by external factors, rather than actively contributing to disease processes. The exact role of HERVs in RA pathology remains elusive; however this research proposes several mechanisms by which HERV-K (HML-2) may contribute to disease.
