Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 22037116 | Vaccination of patients with auto-immune inflammatory rheumatic diseases requires careful | 2012 Jun | Will vaccination raise the incidence of autoimmune diseases, what is the impact of increasingly crowded vaccination schedules, the vaccination in age groups and the risk of coincidental temporal association? All these issues are still under debate. However, for the time being, to avoid confusion in the medical community and the media, we have to adhere to guidelines established consensually by experts while ensuring a strict surveillance and reporting possible side effects. Recommendation for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD) based on the currently available evidence and expert opinion were recently formulated by an EULAR task force. Major recommendations for AIIRD include: i) vaccination should ideally be administered during stable disease; ii) influenza vaccination and pneumococcal vaccination should be strongly considered; iii) vaccination can be administered during the use of DMARDs and TNF-inhibitors, but before starting rituximab; iv) live attenuated vaccines should be avoided whenever possible in immunosuppressed patients; v) BCG vaccination is not recommended. | |
| 22035625 | Central sensitization in patients with rheumatoid arthritis: a systematic literature revie | 2012 Feb | OBJECTIVE: The goal of the present study is to systematically review the scientific literature addressing central sensitization and central nociceptive processing in patients with rheumatoid arthritis (RA). METHODS: To identify relevant articles, we searched PubMed and Web of Science. The search strategy was a combination of terms of the following groups: "Rheumatoid arthritis," inflammatory joint pain, or arthritis; AND (central) sensitization, (central) hypersensitivity, central hyperexcitability, pain modulation, pain processing, neural inhibition, or pain physiopathology; AND pain, nociception, hyperalgesia, pain threshold, or algometry. Articles fulfilling the inclusion criteria were screened for methodologic quality with specific checklists to evaluate different study designs (2 independent raters). RESULTS: Twenty-four full-text articles were included, of which the majority were case-control studies, followed by nonsystematic reviews, cross-sectional studies, and case reports. Methodologic quality was very heterogeneous. Preliminary evidence for generalized hyperalgesia in RA is available. In addition, the mechanism behind impaired central nociceptive processing remains rather obscure. The role of cytokines and neuropeptides especially remains to be elucidated. Windup appears to develop more easily in RA, but evidence in support of impaired nociceptive inhibition and cognitive emotional sensitization (sensitization due to cognitive bias) is scarce. CONCLUSIONS: The symmetrical manifestation of the disease, the poor relation between disease activity and symptoms, and the generalized hyperalgesia at both articular and nonarticular sites for different kinds of stimuli are indicative of the presence of central sensitization in RA patients. Further research is required to provide firm evidence in support of various aspects of central sensitization in humans with RA. | |
| 21446881 | IL-33: a promising therapeutic target for rheumatoid arthritis? | 2011 May | Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA). Recently, the IL-1-family-related cytokine, IL-33, was detected at high levels in experimental inflammatory arthritis and in the early phase of human RA, and was reported to exert profound pro-inflammatory effects in several experimental autoimmune models. Moreover, administration of IL-33 leads to the development of severe inflammatory arthritis, suggesting that IL-33 may be therapeutically relevant in RA, and the targeting of IL-33 or the IL-33 receptor has been proposed as a potential therapeutic approach for autoimmune diseases such as RA. In this article, we discuss the biological features of IL-33 and summarize recent advances in our understanding of the role of IL-33 in the pathogenesis and treatment of RA. It is hoped that this information may aid the development of novel therapeutic strategies for RA. | |
| 21323707 | What can the periodontal community learn from the pathophysiology of rheumatoid arthritis? | 2011 Mar | AIM: The aim of this paper is to provide a narrative review of the aetiopathogeneis and treatments of rheumatoid arthritis (RA), focusing on aspects that may share commonality with periodontitis. RESULTS: A myriad of cell types, cytokines and pathways have been investigated in both periodontitis and RA. Chronic inflammatory diseases, including RA, psoriatic arthritis, ankylosing spondylitis and periodontitis are likely to share pathogenic mechanisms of inflammation-mediated solid tissue destruction. The aetiopathogenesis of these diseases has been extensively researched over the last several decades and advances in understanding have revolutionized arthritis therapeutics. CONCLUSION: The rational, targeted inhibition of mediators in RA has provided clinically useful therapeutics and shed light on mechanisms underpinning disease pathogenesis. RA should be considered a prototypic disease revealing how understanding disease pathogenesis may transform therapeutic options and patient outcomes. | |
| 21071175 | Novel autoantibody markers for early and seronegative rheumatoid arthritis. | 2011 Feb | Approximately one-third of rheumatoid arthritis (RA) patients are seronegative for the 2 serological RA markers, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACCP). Moreover, the sensitivities of both markers are lower in the diagnostically important early disease phase. The aim of this study was to identify additional autoantibody markers for early RA and for RF-negative, ACCP-negative (seronegative) RA. We screened an RA synovium cDNA phage display library with autoantibodies in plasma from 10 early (symptoms of maximum 1 year) and 10 seronegative (RF-negative, ACCP-negative) RA patients with validation in 72 additional RA patients and 121 controls (38 healthy controls, 43 patients with other inflammatory rheumatic diseases, 20 osteoarthritis patients and 20 subjects with mechanical joint complaints). Fourteen novel autoantibodies were identified that showed a 54% sensitivity and 90% specificity for RA. For 11 of these autoantibodies, an exclusive presence was demonstrated in RA patients (100% specificity, 37% sensitivity) as compared to controls. All early RA patients were positive for at least one of the identified autoantibodies and antibody-positivity was associated with a shorter disease duration (P = 0.0087). 52% of RA patients who initially tested negative for RF and ACCP, tested positive for at least one of the 14 novel autoantibodies, resulting in a 19% increase in sensitivity compared to current serological testing. Moreover, 5 identified autoantibodies were detected more frequently in seronegative RA patients, indicating that these autoantibodies constitute novel candidate markers for this RA subtype. We demonstrated that the targets of 3 of these 5 autoantibodies had an increased expression in RA synovial tissue compared to control synovial tissue, pointing towards a biological rationale for these auto antibody targets in RA. In conclusion, we identified novel candidate autoantibody markers for RA that can be detected in early and seronegative RA patients indicating the potential added value for RA diagnostics. | |
| 20851025 | Blood vessels, a potential therapeutic target in rheumatoid arthritis? | 2011 Mar | New micro-vessels formation within synovium and macro-vessels endothelial damage with atheroma are two major features of rheumatoid arthritis, the former related to the articular involvement of the disease, the latter to its main systemic complication. The similarities between pannus development and solid tumors growth, and the efficacy of anti-angiogenic treatments in oncology, opened the perspective of directly targeting angiogenesis in arthritis. Nevertheless, despite the success of different anti-angiogenic therapeutic strategies in many arthritis experimental models, the application in human disease is still lacking. Recent data suggest that synovial neoangiogenesis and macro-vessels endothelial damage might be two linked phenomena. While synovial angiogenesis seems to be detrimental to endothelial damage repair, even anti-angiogenic treatments might paradoxically aggravate macro-vascular disease, especially in the context of uncontrolled inflammation. These elements induce to further explore the interconnections between inflammation and angiogenesis on one side and between micro- and macro-vascular diseases on the other, in order to establish the proper way to therapeutically target blood vessels in rheumatoid arthritis. | |
| 23296189 | Spectroscopic assessment of endogenous porphyrins in a rheumatoid arthritis rabbit model a | 2013 Feb 5 | The sensitization of inflamed knee tissues with endogenous porphyrins was studied by means of fluorescence spectroscopy in an experimental model of rabbit rheumatoid monoarthritis after intraarticular (i.a.) or intravenous (i.v.) injections of 5-aminolevulinic acid (ALA) or ALA methyl ester (ALA-Me). Fluorescence measurements in vivo on the skin of the inflamed knee joint showed the dominance of protoporphyrin IX (PpIX). The highest fluorescence intensity was registered 2h after i.a. injection of ALA and ALA-Me. Comparative analysis of the PpIX fluorescence spectra ex vivo revealed that more PpIX accumulated in the tissues of the inflamed joint than in the tissues of the control joint, and that ALA-Me induced about five times more PpIX in the inflamed synovium than ALA. Meanwhile, the cartilages of the inflamed and control knee joints also accumulated water-soluble porphyrins. Thus, in vivo and ex vivo spectroscopic assessment of endogenous porphyrins in rabbit rheumatoid arthritis tissues implied that the injection of ALA is more appropriate for the diagnostics of inflammation due to the higher PpIX fluorescence intensity on the skin surface, while ALA-Me is more appropriate for the therapeutic applications due to the higher and more selective accumulation of PpIX in the inflamed synovium. | |
| 22472927 | Markers of progression to rheumatoid arthritis: discriminative value of the new ACR/EULAR | 2011 Oct | OBJECTIVES: Our goal was to test the performance of the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for the classification of rheumatoid arthritis (RA) in a cohort of patients with very recent onset polyarthritis. PATIENTS: Untreated polyarthritis patients with less than 6 weeks of duration were enrolled. All patients were followed-up in order to establish a definitive diagnosis. RESULTS: Thirty-seven patients were included. During the follow up 57% of the patients evolved to RA. The median age of the RA-group patients was simiÂlar to the median age of the non-RA group [median (IQR) 47 (31-58.5) vs 43 (34-69) years, p=0.74]. At the initial visit the DAS 28 in the RA group was significantly higher than in the non-RA group, as well as the visual analogue scale (VAS), the HAQ and the number of swollen joints. Among the 21 RA patients, 43% presented RF and 28.6% presented anti-citrullinated protein antibody (ACPA) in the first visit. RF and ACPA were not detectable in any of the patients who did not evolve to RA. According to the new ACR/EULAR criteria, the mean total score of the RA group at baseline was significantly higher than the non-RA group [median (IQR) 6 (4.5-8) vs 4.5 (2.2-6), p=0.007]. CONCLUSION: In our cohort high DAS28, swollen joint count, VAS and HAQ and the presence of RF or ACPA were eventually associated with the evolution into RA. The new ACR/EULAR criteria for the classification of RA seem to perform well in very early RA. | |
| 22930110 | [German 2012 guidelines for the sequential medical treatment of rheumatoid arthritis. Adap | 2012 Sep | Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered. | |
| 22374437 | [Recent findings on phosphoinositide-3 kinase in rheumatic diseases]. | 2012 | Rheumatic diseases are chronic inflammatory disorders, and many of them are autoimmune diseases. Class I phosphatidylinositol-3 kinases (PI3Ks) are enzymes that phosphorylate phosphoinositides in response to extracellular stimuli and regulates cellular activation, proliferation, and migration, in a variety of cell types, suggesting that they play critical roles in the development of inflammation. In patients with rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), recent reports have shown convincing pathogenic evidence for the involvement of PI3K/Akt signaling pathways in chronic inflammation. Moreover, selective inhibition of PI3K γ reduced incidence and severity of the renal disease. More recently, the kinome array analysis revealed particular up-regulation of PI3K in B cells from patients with SLE in comparison with matched controls. Up-regulation of PI3K in T cells was also reported in patients with SLE. Further, we have demonstrated anti-rheumatic effects of a novel PI3K-specific inhibitor, ZSTK474, in mouse collagen-induced arthritis (CIA). Administration of ZSTK474, even if started after the development of arthritis, ameliorated CIA with no apparent adverse effect. Proliferation of B lymphocytes and synovial fibroblasts were inhibited by ZSTK474 in vitro. ZSTK474 suppressed osteoclast formation in vitro and also in the joints of CIA mice. These findings indicate that PI3K might be a potential therapeutic target of rheumatic diseases. | |
| 21039421 | Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors. | 2011 Feb | Advances in our understanding of the key mediators of chronic inflammation and tissue damage characteristic of rheumatoid arthritis (RA) have resulted in the development of novel therapies primarily targeting pro-inflammatory cytokines. Inhibitors of tumour necrosis factor (TNF) are the most widely used of the biological therapies at present with five different agents currently available; four are based on monoclonal anti-TNF antibodies and a soluble TNF receptor-Fc fusion protein. Long-term use of these molecules has proven to be highly effective in the majority of patients; however, around one-third have a suboptimal response potentially leading to further cartilage and bone damage, furthermore these agents are expensive compared with conventional therapies such as methotrexate. Many recent studies have attempted to identify therapeutic response biomarkers of TNF inhibitors which could be used to improve therapeutic targeting. The presence of rheumatoid factor and anti-cyclic citullinated protein antibodies, present in around 65% of RA patients, are associated with a poorer response to anti-TNF agents. Poorer response is also associated with levels of C-reactive protein and cartilage degradation product at initiation of treatment. Intriguingly, genetic studies of variants of TNF and of genes encoding members of the Toll-like receptors, nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling families have been associated with response to individual anti-TNF agents. Continued advances in technologies such as ultra high throughput sequencing and proteomics should facilitate the discovery of additional biomarkers of response to anti-TNF resulting in improved disease control and quality of life for RA patients and reduced costs for healthcare funders. | |
| 21375157 | Epidemiology of rheumatoid arthritis in a tertiary care unit, Karachi, Pakistan. | 2011 Feb | OBJECTIVE: To determine the frequency, demographic characteristics, associated co- morbidities and extraarticular manifestations in patients with rheumatoid arthritis (RA) visiting the rheumatology clinic at a tertiary care hospital, Karachi. METHOD: A retrospective medical chart review of 4900 patients, who visited the rheumatology clinic at Liaquat National Hospital, from January 2005 to June 2007, was conducted. All patients with RA, of both gender and ages 16 years and above, who fulfilled the 1987 ACR criteria were included. Demographic characteristics, base line co-morbidity and extra-articular manifestations were recorded according to pre-defined criteria. RESULT: Among 4900 patients, 633 (12.9%) visited the rheumatology clinic with RA, female to male ratio being 4:1. The mean age of onset was 38.5 +/- 12.4 years in females and 44.8 +/- 13.12 years in males. Among the age group 16-29 years females were more affected, whereas greater number of males presented between 50-75 years of age. Co-morbidities were found in 35.38% of RA patients. Cardiovascular disease including hypertension (13.79%) and ischaemic heart disease (6.6%) were the most common co-morbidities. RA factor was positive in 85.05% of the patients with hypertension and 88.09% of the patients with ischaemic heart disease. Extra-articular manifestations were reported in 3.47% of patients. Interstitial lung disease (1.57%) was the most common extra-articular manifestation. CONCLUSION: Significant proportion of patients with female predominance visited the rheumatology clinic at a tertiary care hospital due to RA. Rheumatoid factor may predict the risk of developing cardiovascular disease in patients with RA. The frequency of extra-articular manifestation was lower than that reported in western population. | |
| 21953347 | Remission in early rheumatoid arthritis defined by 28 joint counts: limited consequences o | 2012 Jan | Introduction The new American College for Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria are based on the assessment of 28 joints. A study was undertaken to study the consequences of remission misclassification due to residual disease activity in the feet on physical function and joint damage in the subsequent year in an observational early disease cohort. METHODS: All patients with rheumatoid arthritis at inclusion or at 1-year follow-up in the early arthritis cohort of the Jan van Breemen Institute, The Netherlands were included. ACR/EULAR remission definitions for trials and clinical practice were calculated twice, once using a 28-joint count and once using a 38-joint count that included the 10 metatarsophalangeal joints. Disease stability was defined as stable x-ray scores over 1 year (change ≤ 0 in Sharp/van der Heijde scores) and stable and low scores on the Health Assessment Questionnaire (HAQ change ≤ 0 and HAQ score consistently ≤ 0.5), all during the second year after inclusion. Analyses comprised residual disease activity (swollen or tender joints >0) in the feet of patients who fulfilled the candidate remission criteria using a 28-joint count and likelihood ratios of remission definitions to predict disease stability. RESULTS: Of 421 patients, 9-15% reached remission at 1 year using a 28-joint count. Of these, 26-40% showed activity in the feet. Misclassification due to reduced joint counts was observed in 2-3%. A state of remission increased the likelihood of stability of both x-ray and HAQ, with similar likelihood ratios for definitions using 38-joint counts and those using 28-joint counts. CONCLUSION: The ability of remission definitions with 28-joint counts versus 38-joint counts to predict long-term good radiological and functional outcome is similar. This confirms that inclusion of ankles and forefeet in the assessment of remission is not required, although inclusion of these joints in the examination is recommended. | |
| 21960046 | Diagnostic value of anti-cyclic citrullinated peptide antibody for rheumatoid arthritis in | 2012 Oct | To use meta-analysis to determine the accuracy of anti-cyclic citrullinated peptide (CCP) antibody in diagnosis of patients with rheumatoid arthritis (RA) in a Chinese population, we searched MEDLINE and CNKI databases for studies published in English or Chinese between January 2000 and June 2010. Two investigators independently evaluated studies for inclusion, data extraction, and quality assessment. We used a random-effects model to combine estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). One hundred and eighteen studies met our inclusion criteria. All studies were of high quality. The summary estimates for anti-CCP antibody in the diagnosis of RA in a Chinese population were as follows: sensitivity 0.65 (95% confidence interval (CI) 0.65-0.66), specificity 0.95 (95% CI 0.95-0.96), positive likelihood ratio (LR+) 15.84 (95% CI 13.55-18.54), negative likelihood ratio (LR-) 0.33 (95% CI 0.31-0.35), and diagnostic odds ratio (DOR) 51.60 (95% CI 43.64-61.01). With high specificity and moderate sensitivity, anti-CCP antibody tests play an important role in conforming the diagnosis of RA in a Chinese population. | |
| 22450926 | Genetic polymorphisms in key methotrexate pathway genes are associated with response to tr | 2013 Jun | We investigated the effect of single-nucleotide polymorphisms (SNPs) spanning 10 methotrexate (MTX) pathway genes, namely AMPD1, ATIC, DHFR, FPGS, GGH, ITPA, MTHFD1, SHMT1, SLC19A1 (RFC) and TYMS on the outcome of MTX treatment in a UK rheumatoid arthritis (RA) patient cohort. Tagging SNPs were selected and genotyping was performed in 309 patients with predefined outcomes to MTX treatment. Of the 129 SNPs tested, 11 associations were detected with efficacy (P-trend 0.05) including four SNPs in the ATIC gene (rs12995526, rs3821353, rs7563206 and rs16853834), six SNPs in the SLC19A1 gene region (rs11702425, rs2838956, rs7499, rs2274808, rs9977268 and rs7279445) and a single SNP within the GGH gene (rs12681874). Five SNPs were significantly associated with adverse events; three in the DHFR gene (rs12517451, rs10072026, and rs1643657) and two of borderline significance in the FPGS gene. The results suggest that genetic variations in several key MTX pathway genes may influence response to MTX in the RA patients. Further studies will be required to validate these findings and if confirmed these results could contribute towards a better understanding of and ability to predict MTX response in RA. | |
| 21547438 | Bone mineral density and frequency of osteoporosis among Vietnamese women with early rheum | 2011 Oct | Generalised bone mineral density (BMD) reduction often occurs in established rheumatoid arthritis (RA); however, in early RA, there is a disagreement with regard to BMD in the femoral neck and lumbar spine, and there is no available information for the whole body. Therefore, the aims of this study were to investigate the BMD, frequency of osteoporosis and the risk factors for BMD reduction in Vietnamese women with early RA. BMD in the femoral neck, lumbar spine L1-4 and whole body was measured in 105 women with early RA (disease duration ≤3 years) and 105 age-matched healthy women (26-73 years) using a dual energy X-ray absorptiometry. Femoral neck and whole body BMD in women with RA were lower (p < 0.05) than controls, while lumbar spine BMD was similar between two groups. The frequency of osteoporosis in the femoral neck, lumbar spine and whole body in women with RA aged ≥50 were higher (p < 0.05) than controls: 41.8% versus 29.5%, 42.2% versus 37.7% and 37.1% versus 28%, respectively. There were associations between the frequencies of osteoporosis at all sites with postmenopausal status, glucocorticoid use, rheumatoid factor positivity and disease activity with lumbar spine BMD and disease disability with femoral neck and whole body BMD. In conclusion, women with early RA had significantly lower femoral neck and whole body BMD, but had similar lumbar spine BMD compared with controls. The frequency of osteoporosis at all sites was significantly higher in women with RA than controls, suggesting that assessment of BMD should be considered in women with early RA. | |
| 23269567 | The detection of calcium pyrophosphate crystals in the synovial fluid of patients with rhe | 2014 Jan | There are only a few studies dealing with the detection and clinical impact of calcium pyrophosphate (CPPD) crystals in patients with rheumatoid arthritis (RA) published to date. In particular, data determined by the cytospin technique, which is an effective tool to enhance the crystal detection rate, are lacking. The objectives of this study were to determine the prevalence of CPPD crystals in the synovial fluid (SF) of patients with RA and to investigate whether the detection of CPPD crystals is correlated with demographic, clinical and serological features. We examined 113 consecutive SF samples of patients with RA, obtained from therapeutic arthrocentesis of knee joints. After cytocentrifugation, the sediments were examined by polarized microscopy for the occurrence of CPPD crystals. Demographic, clinical and serological data, acquired from the medical records, were compared between crystal-positive and crystal-negative subjects. CPPD crystals were observed in 20 of the 113 cases, representing 17.7%. CPPD-positive and CPPD-negative subjects did not differ significantly in sex, duration of disease, Steinbrocker radiologic stage, disease activity score 28, as well as serum rheumatoid factor and anti-CCP positivity. Patients positively tested for CPPD crystals had a significantly higher age than CPPD-negative patients (p < 0.0001). An age-independent association of long-time treatment with diuretics and CPPD crystal formation was not found. In conclusion, demographic, clinical and serological characteristics of patients with RA were not associated with the occurrence of CPPD crystals. Age was the only significant influencing factor on CPPD crystal formation in patients with RA. | |
| 21859693 | Bone marrow oedema predicts structural progression in a 1-year follow-up of 85 patients wi | 2011 Dec | OBJECTIVES: To identify the predictive factors of MRI-determined structural progression in patients with rheumatoid arthritis (RA) in remission or with low disease activity (LDA). METHODS: In this 1-year longitudinal study, patients with RA in clinical remission (disease activity score (DAS) 44≤1.6) or with LDA (1.6 | |
| 20180124 | Health-related quality of life in rheumatoid arthritis: comparison of RAQoL with other sca | 2011 Jun | Quality of life (QoL) is the gratification taken from life, happiness, and the way human beings perceive their situation within the system of culture and values. Rheumatoid arthritis (RA) is among the main conditions in which QoL is decreased. The aim of this study was to evaluate QoL and related variables in patients with RA. A total of 153 RA patients were included in the study. All patients were evaluated by the rheumatoid arthritis quality of life (RAQoL), Nottingham health profile (NHP), and the health assessment questionnaire (HAQ) scales. Disease activity score 28 (DAS28) was used for measuring disease activity, while the modified Sharp score developed by Van der Heijde was used for evaluating the radiological damage, and visual analog scale-pain (VAS-pain) was used to determine the level of pain. RAQoL had linear relations at high levels with VAS-pain, HAQ, DAS28, and the modified Sharp score (r values 0.86, 0.82, 0.82, and 0.38, respectively) and at a moderate level with disease duration (r 0.18). VAS-pain showed the highest correlation with the pain subgroup of NHP (r 0.91) and the second highest correlation was with RAQoL (r 0.86). As a result, it is concluded that in RA patients RAQoL is an important scale reflecting QoL related with pain, disease activity, functional status, and radiological progression. In our study pain ranked first among the variables that influenced QoL, and this was followed by disease activity and functional status. | |
| 22912672 | Interaction between smoking and HLA-DRB1*04 gene is associated with a high cardiovascular | 2012 | BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints that affects approximately 1% of the population worldwide. The HLA-DRB1 gene locus plays a major role in genetic susceptibility to RA, a condition that has been associated with a high cardiovascular morbidity and mortality in many studies. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work was to investigate which types of HLA class II genes are associated with RA in patients from the Brazilian Amazon and their influence on high cardiovascular risk status in this population. For this purpose, a case-control study was carried out with a total of 350 non-Indian individuals made up of a cohort of 132 consecutive RA sufferers and 218 healthy controls. A χ(2) test showed that HLADRB1*04 (p<0.0016; OR = 1.89; 95% CI = 1.29-2.79) and HLADRB1*10 (p = 0.0377; OR = 3.81; 95% CI = 1.16-12.50) are the major HLA genes associated with susceptibility to RA. A logistic regression model also showed that the interaction between HLADRB1*04 (p = 0.027; OR = 6.02; 95% CI = 1.21-29.7), age (p = 0.0001; OR = 1.26; 95% CI = 1.13-1.39) and smoking (p = 0.0001; OR = 23.6; 95% CI = 4.25-32.1) is associated with a probability of a high cardiovascular risk status at an early age. CONCLUSIONS/SIGNIFICANCE: The results of this study show for the first time that HLA class II type is associated with RA in Brazilian Amazon populations and that a specific interaction between the HLA-DRB1*04 gene and smoking is associated with a high cardiovascular risk status, as initially reported in the European population. This study therefore contributes to an understanding of gene-environment interactions in RA patients. |