Browsing by Subject "Rheumatoid arthritis"

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    Is air pollution a risk factor for rheumatoid arthritis?
    (BioMed Central Ltd, 2015) Essouma, Mickael; Noubiap, Jean
    Rheumatoid arthritis is a chronic inflammatory debilitating disease triggered by a complex interaction involving genetic and environmental factors. Active smoking and occupational exposures such as silica increase its risk, suggesting that initial inflammation and generation of rheumatoid arthritis-related autoantibodies in the lungs may precede the clinical disease. This hypothesis paved the way to epidemiological studies investigating air pollution as a potential determinant of rheumatoid arthritis. Studies designed for epidemiology of rheumatoid arthritis found a link between traffic, a surrogate of air pollution, and this disease. Furthermore, a small case-control study recently found an association between wood smoke exposure and anticyclic citrullinated protein/peptide antibody in sera of patients presenting wood-smoke-related chronic obstructive pulmonary disease. However, reports addressing impact of specific pollutants on rheumatoid arthritis incidence and severity across populations are somewhat conflicting. In addition to the link reported between other systemic autoimmune rheumatic diseases and particulate matters/gaseous pollutants, experimental observation of exacerbated rheumatoid arthritis incidence and severity in mice models of collagen-induced arthritis after diesel exhaust particles exposure as well as hypovitaminosis D-related autoimmunity can help understand the role of air pollution in rheumatoid arthritis. All these considerations highlight the necessity to extend high quality epidemiological researches investigating different sources of atmospheric pollution across populations and particularly in low-and-middle countries, in order to further explore the biological plausibility of air pollution's effect in the pathogenesis of rheumatoid arthritis. This should be attempted to better inform policies aiming to reduce the burden of rheumatoid arthritis.
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    Osteoporosis in rheumatoid arthritis
    (1989) Kalla, Asgar Ali; Meyers, O L
    The literature is replete with reports of osteoporosis in rheumatoid arthritis, but the mechanism of bone loss remains obscure. This is probably due to the overlap with bone loss of aging and the menopause, whose exact mechanisms are also poorly understood. Against this background, a study was designed to evaluate generalised bone loss in young, premenopausal (if female), patients with rheumatoid arthritis. The protocol was designed to record demographic data, as well as information pertaining to the disease. Cortical bone mass was measured at the metacarpals and left femur, using an automated, computer-controlled technique. Trabecular bone was evaluated at the left femur (Singh index) as well as at the 3rd lumbar vertebra (Saville index). Bone kinetics were studied by the measurement of urinary excretion of calcium, phosphate and hydroxy-praline (resorption) and serum alkaline phosphatase (formation). Disease activity was measured clinically and with laboratory indices. Physical activity was indirectly measured by quantitating the disability, using the Keitel function test as well as a modified health assessment questionnaire (HAQ). The radiograph of the right wrist was scored by the Larsen index. The carpometacarpal ratio was also calculated from the radiograph. Numerous statistical techniques were applied in the analysis of the data. Healthy volunteers were used as controls. Patients with SLE were also studied, in order to compare the 2 inflammatory diseases. Patients with RA had generalised cortical bone loss (metacarpal and femur) (p < 0.001). Trabecular bone measurements were not significantly different from normals, using the crude radiographic techniques. Duration of disease was the most important clinical determinant of this bone loss. The relative contributions of disease activity and lack of physical activity to the loss of bone could not be adequately separated using conventional statistical techniques. Corticosteroid therapy did not promote metacarpal bone loss in these subjects, but may have contributed to thinning of the femoral cortex. Nonsteroidal anti-inflammatory drugs and disease modifying agents did not seem to influence the extent of the bone loss. Nutritional status and skinfold thickness did not correlate with bone mass. Dietary factors played no role in the genesis of bone loss, but may have had some effect on disease activity. Metacarpal measurements showed a sensitivity of 80% and specificity of 85% in discriminating between osteopaenic and normopaenic groups with RA. Osteopaenia could not be adequately predicted in the absence of metacarpal measurements. Metacarpal bone loss in RA was due to endosteal resorption, while in SLE it was due to periosteal resorption. The semi-automatic technique for measurement of metacarpal bone mass showed good reproducibility among 5 observers and at 2 different centres. The pathogenesis of bone loss in RA was multifactorial, the largest contribution probably coming from a humoral factor in the circulation, closely related to disease activity. Ionised calcium was elevated in 55% of RA patients, but only 5% of SLE patients. Serum PTH levels were normal in 99% of the RA subjects. Elevations in alkaline phosphatase. (25%) probably reflected disease activity rather than increased bone formation. Factor analysis of 27 variables showed that disease activity was central to the development of OP in RA. CS therapy tended to be used in the presence of active disease. Disability was not an important determinant of bone loss in RA, but may be a useful measure of activity of the disease. This study did not evaluate the relationships with sex hormonal status or vitamin D metabolism. Future research should aim at cohort analysis at 2 different periods, in order to improve our understanding of the pathogenesis of bone loss in RA.
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    Points to consider in cardiovascular disease risk management among patients with rheumatoid arthritis living in South Africa, an unequal middle income country
    (2020-06-16) Solomon, Ahmed; Stanwix, Anne E; Castañeda, Santos; Llorca, Javier; Gonzalez-Juanatey, Carlos; Hodkinson, Bridget; Romela, Benitha; Ally, Mahmood M T M; Maharaj, Ajesh B; Van Duuren, Elsa M; Ziki, Joyce J; Seboka, Mpoti; Mohapi, Makgotso; Jansen Van Rensburg, Barend J; Tarr, Gareth S; Makan, Kavita; Balton, Charlene; Gogakis, Aphrodite; González-Gay, Miguel A; Dessein, Patrick H
    Background It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients. Methods Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines. Results Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management (n = 4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs (n = 3), lipid lowering agents (n = 8), antihypertensive drugs (n = 1), low dose aspirin (n = 1) and lifestyle modification (n = 1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound. Conclusions Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA.
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    Presisposing and protective HLA-DR and DQ alleles for rheumatoid arthritis in South African mixed-ancestry and Xhosa populations
    (2003) Rousseau, J; Pokorny, L; Glaser, J; Creemers, P C
    We have investigated the distribution of the HLA-DRB1, -DQA1 and -DQB1 alleles in rheumatoid arthritis (RA) by comparing the allele frequencies in blood from 65 Cape coloured (mixed-ancestry) RA patients and 114 controls, and from 25 Xhosa RA patients and 94 controls. The strongest positive association with RA was found for the DRB10401 allele, followed by the DQA10301 and DQB10302 alleles, which are strongly linked with DRB10401. Data for both populations were statistically significant. In addition, DQB10501, which is in linkage disequilibrium with DR1 and DR10, showed a positive association with RA. These findings are in agreement with those for Caucasoids; they indicate that haplotypes that predispose for RA are highly conserved during evolution. Negative associations, that is, a protective effect for RA, were also found, but only for broad specificities; the associations were generally weaker. New findings were negative associations for DRB103, DRB10701, DQA10501 and DQB106. The DRB10301 and DQA10501 alleles are in linkage disequilibrium; a negative association was found in both populations. The negative association of DRB10701 was found only in the mixed-ancestry population and was absent in Xhosa. The effect of DQA106 was significant in both populations. Thus, the protective HLA-DR and DQ alleles show a greater ethnic diversity.
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    Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells
    (BioMed Central, 2018-06-08) Talbot, Jhimmy; Peres, Raphael S; Pinto, Larissa G; Oliveira, Rene D R; Lima, Kalil A; Donate, Paula B; Silva, Jaqueline R; Ryffel, Bernard; Cunha, Thiago M; Alves-Filho, José C; Liew, Foo Y; Louzada-Junior, Paulo; de Queiroz Cunha, Fernando
    Background Epidemiologic studies have highlighted the association of environmental factors with the development and progression of autoimmune and chronic inflammatory diseases. Among the environmental factors, smoking has been associated with increased susceptibility and poor prognosis in rheumatoid arthritis (RA). However, the immune and molecular mechanism of smoking-induced arthritis aggravation remains unclear. The transcription factor aryl hydrocarbon receptor (AHR) regulates the generation of Th17 cells, CD4 T cells linked the development of autoimmune diseases. AHR is activated by organic compounds including polycyclic aromatic hydrocarbons (PAHs), which are environmental pollutants that are also present in cigarette smoke. In this study, we investigated the role of AHR activation in the aggravation of experiment arthritis induced by exposure to cigarette smoke. Methods Mice were exposed to cigarette smoke during the developmental phase of antigen-induced arthritis and collagen-induced arthritis to evaluate the effects of smoking on disease development. Aggravation of articular inflammation was assessed by measuring neutrophil migration to the joints, increase in articular hyperalgesia and changes in the frequencies of Th17 cells. In vitro studies were performed to evaluate the direct effects of cigarette smoke and PAH on Th17 differentiation. We also used mice genetically deficient for AHR (Ahr KO) and IL-17Ra (Il17ra KO) to determine the in vivo mechanism of smoking-induced arthritis aggravation. Results We found that smoking induces arthritis aggravation and increase in the frequencies of Th17 cells. The absence of IL-17 signaling (Il17ra KO) conferred protection to smoking-induced arthritis aggravation. Moreover, in vitro experiments showed that cigarette smoke can directly increase Th17 differentiation of T cells by inducing AHR activation. Indeed, Ahr KO mice were protected from cigarette smoke-induced arthritis aggravation and did not display increase in TH17 frequencies, suggesting that AHR activation is an important mechanism for cigarette smoke effects on arthritis. Finally, we demonstrate that PAHs are also able to induce arthritis aggravation. Conclusions Our data demonstrate that the disease-exacerbating effects of cigarette smoking are AHR dependent and environmental pollutants with AHR agonist activity can induce arthritis aggravation by directly enhancing Th17 cell development.
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    Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients
    (BioMed Central Ltd, 2015) Essouma, Mickael; Noubiap, Jean
    Rheumatoid arthritis (RA) is a chronic inflammatory disease that preferentially affects joints, and characterized by an approximately two-fold increased risk of cardiovascular diseases compared with the general population. Beyond classical cardiovascular risk factors, systemic inflammatory markers are primarily involved. Hence, anti-inflammatory strategies such as homocysteine-lowering interventions are warranted. Indeed, hyperhomocysteinemia is commonly found in RA patients as a result of both genetic and non-genetic factors including older age, male gender, disease-specific features and disease-modifying antirheumatic drugs. Most importantly in the pathophysiology of hyperhomocysteinemia and its related cardiovascular diseases in RA, there is a bi-directional link between immuno-inflammatory activation and hyperhomocysteinemia. As such, chronic immune activation causes B vitamins (including folic acid) depletion and subsequent hyperhomocysteinemia. In turn, hyperhomocysteinemia may perpetrate immuno-inflammatory stimulation via nuclear factor appa B enhancement. This chronic immune activation is a key determinant of hyperhomocysteinemia-related cardiovascular diseases in RA patients. Folate, a homocysteine-lowering therapy could prove valuable for cardiovascular disease prevention in RA patients in the near future with respect to homocysteine reduction along with blockade of subsequent oxidative stress, lipid peroxidation, and endothelial dysfunction. Thus, large scale and long term homocysteine-lowering clinical trials would be helpful to clarify the association between hyperhomocysteinemia and cardiovascular diseases in RA patients and to definitely state conditions surrounding folic acid supplementation. This article reviews direct and indirect evidence for cardiovascular disease prevention with folic acid supplementation in RA patients.