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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
24770512 Arthritis and diagnosis of leprosy: a case report and review of the literature. 2014 Mar Leprosy is clinically characterized by involvement of peripheral nerves and skin. The immunological profile of the individual defines the diversity of clinical manifestations, from skin disorders to systemic manifestations, especially the articulation ones, common in multibacillary forms, which may mimic collagen diseases and often posing diagnostic difficulties in endemic areas. This is a case report of asymmetric polyarthritis of small and large articulations associated with skin lesions which had been treated by a rheumatologist for 2 years with initial clinical diagnosis of rheumatoid arthritis, and later, with the appearance of skin lesions, of systemic lupus erythematosus.
25179847 Extraarticular manifestations of rheumatoid arthritis develop in patients receiving anti-t 2014 Oct OBJECTIVE: To assess the evolution of preexisting extraarticular manifestations of rheumatoid arthritis (EA-RA) in patients treated with anti-tumor necrosis factor-α (TNF-α), as well as the development of new EA-RA. METHODS: We assessed EA-RA in 152 patients receiving anti-TNF-α treatment. RESULTS: In 22 cases, a new EA-RA developed. In 5 cases, there was evidence of progression of preexisting EA-RA. Regression was found in 4 cases. Some patients were in disease remission when they developed EA-RA, whereas some patients had moderate/high disease activity. CONCLUSION: EA-RA are still present in patients treated with anti-TNF-α. Development of new severe EA-RA is rare in patients receiving anti-TNF therapy.
23731635 Osteoclasts in RA: diverse origins and functions. 2013 Dec Osteoclasts were recognized in the late 1990s as the cells responsible for generalized and focal bone loss in rheumatoid arthritis (RA). Concepts about osteoclast biology have changed radically based on recent evidence of considerable diversity in both the origins and the functions of osteoclasts. In addition, the role for osteoclasts is not confined to bone resorption but may also include active contributions to inflammatory and autoimmune responses. Thus, in RA, osteoclast progenitors may arise from both circulating cells and cells developed within the rheumatoid synovium or subchondral bone. Within the inflamed synovium, osteoclasts are activated by factors such as cytokines, immune complexes, or activators of the toll-like receptors, which are not found in healthy bone tissue. Finally, recent data suggest that osteoclasts may be capable of antigen presentation to T cells via major histocompatibility complex class I and class II molecules. Confirmation of this suggestion by future studies would indicate that osteoclasts might be involved not only in bone resorption, but also in autoimmune responses and antigen presentation. These data highlight the considerable complexity of interactions between bone tissue and the immune system. Research into these interactions may identify new targets for treatments against the bone abnormalities associated with chronic inflammatory disease.
22532640 A systematic literature review of strategies promoting early referral and reducing delays 2013 Jan BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.
25164131 Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells i 2014 Nov The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3(+) CD4(+) IL-17(+) Th17 cells were significantly higher, and CD4(+) CD25(+) FOXP3(+) Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro-inflammatory cytokines, including IL-17, IL-6, IL-1β, TNF-α and IL-22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR-21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up-regulated miR-21 expression from healthy controls, but down-regulated miR-21 expression from RA patients. Therefore, we speculate that miR-21 may be part of a negative feedback loop in the normal setting. However, miR-21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR-21 may thus serve as a novel regulator in T-cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA.
25143522 How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate d 2015 Jun OBJECTIVES: Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) is used instead of erythrocyte sedimentation rate (DAS28-ESR) to assess rheumatoid arthritis disease activity; however, values for remission and low disease activity (LDA) for DAS28-CRP have not been validated. American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guidelines suggest remission should be calculated by Simplified Disease Activity Index (SDAI) rather than DAS28-ESR. We examined values of remission and LDA of DAS28-CRP that correspond to the respective cut-off points for DAS28-ESR and SDAI from five clinical trials. METHODS: DAS28-CRP cut-offs that best correspond to DAS28-ESR remission <2.6 and LDA ≤3.2 were obtained by cumulative distribution plots, receiver operating curves and maximum concordance and averaged for each approach, treatment group and study. Level of agreement between DAS28-CRP and DAS28-ESR remission and LDA cut-offs was compared against each other and versus SDAI remission ≤3.3 and LDA ≤11. RESULTS: Percentage of patients who achieved remission and LDA by DAS28-ESR cut-offs was greater for DAS28-CRP versus DAS28-ESR regardless of patient population or treatment group. Discordance between CRP and ESR cut-offs ranged from 4%-26% and 8%-23% for remission and LDA, respectively, and 19%-40% and 6%-11% for DAS28-CRP versus SDAI, respectively. Estimated (range) remission and LDA thresholds were 2.4 (2.2-2.6) and 2.9 (2.6-3.3), 1.9 (1.6-2.2) and 3.1 (3.1-3.3) and 2.2 (1.1-2.9) and 3.6 (3.4-4.0) for DAS28-CRP versus DAS28-ESR, DAS28-CRP versus SDAI and DAS28-ESR versus SDAI, respectively. CONCLUSIONS: DAS28-CRP underestimates disease activity when using cut-off points validated for DAS28-ESR; therefore, DAS28-ESR cut-off values should not be applied to DAS28-CRP. Although DAS28-CRP and DAS28-ESR cut-offs for LDA ≤3.2 correspond to SDAI LDA, neither corresponds well to SDAI remission.
25496404 Predictive value of bone destruction and duration of clinical remission for subclinical sy 2015 Jul OBJECTIVES: Treatment for rheumatoid arthritis (RA) should aim to achieve full remission. The aim of this study was to investigate predictors of persistent subclinical synovitis and whether longer clinical remission is effective in reducing subclinical synovitis. METHODS: Forty-four RA patients who achieved DAS28ESR clinical remission for at least 3 months were enrolled in this study and underwent ultrasound examination of 22 joints (bilateral proximal interphalangeal joints, metacarpophalangeal joints, and wrists); bilateral hand X-ray; and blood examination. The severity of synovial effusion, synovial hypertrophy, and blood flow were semi-quantitatively graded from 0 to 3 using gray-scale (GS) and power Doppler (PD) modes. RESULTS: Among patients with DAS28ESR-defined clinical remission, 59.1% (26/44) demonstrated residual synovitis (≥ PD1) in at least one joint. Genant-modified total Sharp score (TSS) demonstrated the highest statistical difference between patients with and without residual subclinical synovitis (p = 0.0057), and full remission was only observed in patients with low TSS. A nonsignificant trend for decreased residual synovitis with longer sustained clinical remission was also observed (p = 0.724). CONCLUSION: Residual synovitis can persist during clinical remission, particularly in patients with progressive bone destruction. Early treatment and longer sustained clinical remission prior to bone destruction are critical for full remission.
24018427 Effect of allograft inflammatory factor-1 gene polymorphisms on rheumatoid arthritis treat 2013 Jul 18 OBJECTIVE: Methotrexate (MTX) in low doses is used in the therapy of rheumatoid arthritis (RA). The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatoid arthritis. The action of MTX in RA is associated with the inhibition of inflammatory mediators synthesis. AIF-1 is a cytokine playing a role in chronic inflammatory processes. The levels of AIF-1 were significantly increased in synovial fluid from patients with RA. The aim of this study was to investigate the association between AIF1 gene polymorphisms (rs2269475:C>T, rs2736182:G>A, rs2259571:A>C) and response to treatment of RA patients with MTX. MATERIAL AND METHODS: The study was carried out on 221 patients diagnosed with active rheumatoid arthritis, treated with MTX. Good responders were defined as patients who were receiving MTX and had a DAS28 of ≤2.4 at 6 months. RESULTS: With regard to the AIF1 rs2259571 polymorphism the remission of RA symptoms was observed in 52.99% of AA genotype carriers, in 45.25% of subjects with AC genotype, and in 32.84% with CC. The differences were statistically significant. CC vs AA p=0.03, OR 0.41, 95%CI (0.18-0.92). CONCLUSION: The results of this study suggest that the patients with the rs2259571 CC AIF1 genotype have a poorer response to therapy with MTX.
25369438 Neurologic complications of systemic lupus erythematosus, sjögren syndrome, and rheumatoi 2014 Sep Neurologic complications are frequent and often morbid in systemic lupus erythematosus, Sjögren syndrome, and rheumatoid arthritis. Although all are systemic inflammatory syndromes, each disease affects the nervous system distinctly, such as peripheral neuropathy in Sjögren syndrome, cerebrovascular disease in lupus, and cervical spine subluxation in rheumatoid arthritis. Some neurologic complications share convergent pathophysiology across diseases, such as neuromyelitis optica spectrum disorders in both Sjögren syndrome and lupus. Ill-defined cognitive complaints are especially common in lupus and Sjögren syndrome. For the majority of the complications, evidence for treatment efficacy is limited and requires further investigation.
25662926 Why currently used diagnostic techniques for heart failure in rheumatoid arthritis are not 2014 Rheumatoid arthritis (RA) is a multiorgan inflammatory disorder affecting approximately 1% of the population that leads to progressive joint destruction and disability. Patients with RA exhibit a high risk of cardiovascular disease, which results in premature morbidity and mortality and reduced life expectancy, when compared with the general population. Among various guises of myocardial involvement, heart failure (HF) has been recently recognized as an important contributory factor to the excess cardiovascular mortality associated with RA. HF in RA typically presents with occult clinical symptomatology and is mainly associated with structural and functional left ventricular abnormalities leading to diastolic dysfunction, while systolic myocardial performance remains well preserved. As isolated diastolic dysfunction is a predictor of high mortality, the evaluation of patients in early asymptomatic stages, when treatment targeting the heart is more likely to be effective, is of great importance. Although patient history and physical examination remain the cornerstones of HF evaluation, noninvasive imaging of cardiac chambers, coronary arteries, and great vessels may be necessary. Echocardiography, nuclear techniques, and invasive coronary angiography are already established in the routine assessment of HF; however, many aspects of HF pathophysiology in RA remain obscure, due to the limitations of currently used techniques. The capability of cardiovascular magnetic resonance (CMR) to capture early tissue changes allows timely detection of pathophysiologic phenomena of HF in RA, such as myocardial inflammation and myocardial perfusion defects, due to either macrovascular (coronary artery disease) or microvascular (vasculitis) disease. Therefore, CMR may be a useful tool for early, accurate diagnosis and research in patients with RA.
23434571 The type I IFN signature as a biomarker of preclinical rheumatoid arthritis. 2013 May OBJECTIVES: To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development. METHOD: In 115 seropositive arthralgia patients who were followed for the development of arthritis (Amsterdam Reade cohort), and 25 presymptomatic individuals who developed rheumatoid arthritis (RA) later, and 45 population-based controls (Northern Sweden cohort), the expression levels of 7 type I IFN response genes were determined with multiplex qPCR and an IFN-score was calculated. The diagnostic performance of the IFN-score was evaluated using Cox regression and Receiver Operating Characteristics (ROC)-curve analysis. RESULTS: In 44 of the 115 at-risk individuals (38%) from the Amsterdam Reade cohort, arthritis developed after a median period of 8 months (IQR 5-13). Stratification of these individuals based on the IFN-score revealed that 15 out of 25 IFN(high) individuals converted to arthritis, compared with 29 out of 90 IFN(low) individuals (p=0.011). In the Northern Sweden cohort, the level of the IFN-score was also significantly increased in presymptomatic individuals who developed RA compared with population-based controls (p=0.002). Cox regression analysis of the Amsterdam Reade cohort showed that the hazard ratio (HR) for development of arthritis was 2.38 (p=0.008) for IFN(high) at-risk individuals after correction for anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The ROC-curve area under the curve (AUC) for the IFN-score combined with ACPA and RF in the prediction of arthritis was 78.5% (p=0.0001, 95% CI 0.70 to 0.87). CONCLUSIONS: The results demonstrated clinical utility for the IFN-signature as a biomarker in the prediction of arthritis development.
23965481 A Renaissance Pope with arthritis following frostbite. 2013 Sep Pius II, a 15th century Pope, developed chronic foot pain following frostbite at age 30. Later in life he was progressively disabled by arthritis elsewhere and by colic, which may have been due to kidney stones. The differential diagnosis of his rheumatic disease and its effect on his career are discussed.
25437289 Identification of self-antigen-specific T cells reflecting loss of tolerance in autoimmune 2014 Nov Despite treatment advances, rheumatoid arthritis (RA) is still associated with significant disability, decreased work capacity, and reduced life expectancy. Effective immunotherapies to restore immune tolerance promise greater specificity, lower toxicity, and a longer-term solution to controlling and preventing RA. Design of effective therapies requires a fundamental understanding of the critical immunopathogenetic pathways in RA. This article reviews advances in the understanding of self-antigen-specific T cells in autoimmune diseases including RA and type 1 diabetes, which bring exciting insights to the mechanisms underpinning loss of tolerance and how tolerance could be restored for disease prevention in the preclinical or recent-onset period.
25445628 [Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid ar 2014 Nov BACKGROUND: Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage. OBJECTIVES: To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity. METHODS: 80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method. RESULTS: A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I. CONCLUSION: There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status.
24781621 Disease activity, knee function, and walking ability in patients with rheumatoid arthritis 2014 Apr PURPOSE: To evaluate disease activity, knee function, and walking ability of patients with rheumatoid arthritis (RA) over 10 years after total knee arthroplasty (TKA). METHODS: Four men and 26 women (mean age, 59.9 years) underwent 42 TKAs for RA with a mean duration of 151.3 months and were followed up for a mean of 142.3 months. Preoperatively, disease activity was assessed by C-reactive protein (CRP) level only, and the range of knee motion was recorded. At the final follow-up, tender joint count, swollen joint count, visual analogue scale of RA symptoms, and the Modified Health Assessment Questionnaire (MHAQ) score were assessed. Disease activity was evaluated using CRP, matrix metalloproteinase-3, and Disease Activity Score. Range of motion and Knee Society knee and function scores were also assessed. RESULTS: The use of methotrexate increased from 4 patients preoperatively to 20 patients at the final follow-up (p<0.001), and the mean dose increased from 3.9 to 6.3 mg/week (p<0.001). Among the 30 patients, the mean CRP level decreased from 2.63 mg/dl preoperatively to 0.61 mg/dl at the final follow-up (p<0.001). Disease activity was controlled. At the final follow-up, disease activity was in remission in 10 patients, low in 11, and moderate in 9. The mean Knee Society knee score was excellent (91.0), but the mean function score was poor (57.0) and diverse. Severe walking disability (function score, <40) was noted in 8 patients (11 TKAs). Knee and function scores did not correlate. CONCLUSION: Walking ability in patients with RA after TKA was generally poor. Poor function was associated with a history of spinal or lower extremity fracture surgery and the MHAQ score.
23104728 Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthr 2014 Sep Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by elevated oxidative stress and inflammatory biomarkers. The severe side effects of drug used during such disease necessitate the search for new and safe approaches. Food is a rich source of antioxidants and anti-inflammatory bioactive constituents including phenolic compounds, polyunsaturated fatty acids, phytosterols, toccopherols, and carotenoids. We have a series of publications dealing with the anti-inflammatory activity of different food extracts (as nutraceuticals) in experimental animals (acute and chronic inflammation model) and in clinical study (RA patients). Fish oil, primrose oil, extracts of black cumin, fenugreek, liquorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, and date in addition to the probiotic Bifidobacterium bifidum were the nutraceuticals studied. During these studies, changes in inflammatory biomarkers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), seromucoids, fibrinogen, tumor necrosis factor-α (TNF-α), prostaglandin E2), oxidative stress (malondialdehyde), antioxidant status (total antioxidant capacity, vitamin C, vitamin E, retinol, β-carotene), the level of copper (Cu) and zinc (Zn) and colonic microflora in response to the administration of nutraceuticals have been assessed. Results of these studies showed that the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases, which might be due to the presence of one or more of the above-mentioned phytochemicals. CONCLUSION: Anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA.
25481424 Determinants of MSK health and disability--social determinants of inequities in MSK health 2014 Jun Even in most egalitarian societies, disparities in care exist to the disadvantage of some people with chronic musculoskeletal (MSK) disorders and related disability. These situations translate into inequality in health and health outcomes. The goal of this chapter is to review concepts and determinants associated with health inequity, and the effect of interventions to minimize their impact. Health inequities are avoidable, unnecessary, unfair and unjust. Inequities can occur across the health care continuum, from primary and secondary prevention to diagnosis and treatment. There are many ways to define and identify inequities, according for instance to ethical, philosophical, epidemiological, sociological, economic, or public health points of view. These complementary views can be applied to set a framework of analysis, identify determinants and suggest targets of action against inequity. Most determinants of inequity in MSK disorders are similar to those in the general population and other chronic diseases. People may be exposed to inequity as a result of policies and rules set by the health care system, individuals' demographic characteristics (e.g., education level), or some behavior of health professionals and of patients. Osteoarthritis (OA) represents a typical chronic MSK condition. The PROGRESS-Plus framework is useful for identifying the important role that place of residence, race and ethnicity, occupation, gender, education, socioeconomic status, social capital and networks, age, disability and sexual orientation may have in creating or maintaining inequities in this disease. In rheumatoid arthritis (RA), a consideration of international data led to the conclusion that not all RA patients who needed biologic therapy had access to it. The disparity in care was due partly to policies of a country and a health care system, or economic conditions. We conclude this chapter by discussing examples of interventions designed for reducing health inequity.
24560170 Recommendations for the management of cardiovascular risk in patients with rheumatoid arth 2014 Aug OBJECTIVES: Last recommendations regarding cardiovascular risk (CVR) in rheumatoid arthritis (RA) patients were developed by the EULAR group in 2010. The aim is to update evidence-based recommendations about this worrying health problem. METHODS: We assembled a multidisciplinary workgroup (rheumatologists, endocrinologist, cardiologist, and epidemiologist) and a panel of 28 expert rheumatologists. The study was carried out in two big phases: identifying key areas in the prevention and management of CVR and developing a set of recommendations based on a review of the available scientific evidence and use of the Delphi consensus technique. All this has been developed according to an updating process of evidence-based recommendations. RESULTS: Overall, 25 recommendations were made addressing three complementary areas: CVR assessment tools, patient eligibility for assessment, and treatment strategies for control of CVR. The grade of the recommendations was not substantially modified compared to the original EULAR recommendations, except in two of them, which were upgraded from C to B. These two recommendations are the ones related to the use of corticosteroids and smoking cessation. The new developed recommendations address these two areas: CVR assessment and treatment strategies for control of CVR. CONCLUSIONS: There are substantial gaps in the current knowledge that do not allow classifying properly RA patients based on their actual CVR and to accurately identify those patients who would benefit from CVR assessment. Consequently, studies designed to determine the causal effects of RA disease characteristics on cardiovascular morbidity/mortality and to identify patients at high risk of cardiovascular disease are still needed.
25189266 Association of susceptible genetic markers and autoantibodies in rheumatoid arthritis. 2014 Aug Rheumatoid arthritis (RA) is a chronic autoimmune disorder of unknown aetiology resulting in inflammation of the synovium, cartilage and bone. The disease has a heterogeneous character, consisting of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although, the pathogenesis of RA is incompletely understood, genetic factors play a vital role in susceptibility to RA as the heritability of RA is between 50 and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Non-HLA genes, i.e. tumour necrosis factor-α (TNF-α) within the MHC (major histocompatibility complex) have also been investigated for association with RA. Although, some contradictory results have originated from several studies on TNF-α gene, the data published so far indicate the possible existence of TNF-α gene promoter variants that act as markers for disease severity and response to treatment in RA. The correlation of HLA and non-HLA genes within MHC region is apparently interpreted. A considerable number of confirmed associations with RA and other autoimmune disease susceptibility loci including peptidylarginine deiminase type 4 (PADI4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), signal transducer and activator of transcription (STAT4), cluster of differentiation 244 (CD244) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), located outside the MHC have been reported recently. In this review, we aim to give an update on recent progress in RA genetics, the importance of the combination of HLA-DRB1 alleles, non-HLA gene polymorphism, its detection and autoantibodies as susceptibility markers for early RA disease.
24831057 The lung in ACPA-positive rheumatoid arthritis: an initiating site of injury? 2014 Nov Recent findings have highlighted the potential initiation of ACPA in sites away from the joint. Periodontitis is an example of this concept. This process in the gums appears to be independent of smoking, the main environmental risk factor for ACPA-positive RA. There is extensive literature regarding the potential role of smoking in the pathogenesis of ACPA-positive RA. As a consequence of this strong association, the lung has become the focus of research to determine whether processes within the lung are linked to the generation of ACPA. Here we outline the current body of evidence and explore the hypothesis that the lung as an organ of immune defence has a role in the pathogenesis of the autoimmune disease ACPA-positive RA.