Browse

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

ID PMID Title PublicationDate abstract
21299301 Naturalistically observed sighing and depression in rheumatoid arthritis patients: a preli 2011 Jan OBJECTIVE: This study tested the degree to which naturalistically observed sighing in daily life is a behavioral indicator of depression and reported physical symptoms (i.e., experienced pain and flare days) in rheumatoid arthritis (RA) patients. DESIGN: Thirteen RA patients wore the Electronically Activated Recorder (EAR), an observational ambulatory assessment tool, for two weekends (Friday through Sunday) approximately one month apart. The EAR periodically recorded snippets of ambient sounds from participants' momentary environments (50 s every 18 min). Sighs were coded from the sampled ambient sounds. MAIN OUTCOME MEASURES: Depression was assessed with the Center for Epidemiological Studies Depression Scale and the Beck Depression Inventory. Pain during the past month was assessed with a 10-cm visual-analog scale, and number of flare days during the prior 6 months was reported. RESULTS: Sighing was significantly and strongly related to patients' levels of depression and nonsignificantly and less strongly related to their reported pain and number of flare days. CONCLUSION: The findings suggest that sighing can serve as an observable marker of depression in RA patients. Because the sample size was small, the findings should be considered preliminary.
23214198 Estimation of patient knowledge on rheumatoid arthritis in the range of their own disease- 2012 May BACKGROUND: Knowledge is an essential element of treatment which allows patients to take care of themselves, to undertake every day activities and to make decisions essential from the point of view of health. A patient suffering from rheumatoid arthritis needs support, assistance from his family and from medical staff. It depends on him how much the disease will change his life and how he will cope with all the problems related to the psychological, physical and social aspects of life. Each patient should know what his disease is. If he does not receive this information from the qualified staff, he will try to find some information from different sources and then the information may be incomplete and may provoke negative reactions which will make the process of treatment more difficult. OBJECTIVES: Defining the source of the patient's knowledge about his disease and the role and tasks of health education in transferring knowledge to the patient and in building his attitude to the treatment. Increasing participation of a therapeutic team in health education in order to propagate the awareness and need of prevention and physical effort for bringing back normal state of health. MATERIAL AND METHODS: The subject of studies included 270 people with rheumatoid arthritis. The patients examined were treated in the Clinic of Rheumatology and Internal Diseases of the University of Wroclaw since 1st February, 2010 till 15th February, 2011. A self-made questionnaire was used for studies, aimed at obtaining basic information about patients with a diagnosed rheumatoid arthritis. Statistical calculations were made with package Statistica 9 PL. Tests on essentiality of differences were calculated with T-Student test for quantitative data and chi2 test for qualitative data. Abroad, the level of significance was a value of 0.05. RESULTS: The examined patients were divided into 2 groups according to gender. These groups were similar in respect of age, place of residence, professional activity, working time and co-existing diseases excluding osteoporosis which was more frequent in women. A higher level of education was represented by women who were single or widowed or suffered from rheumatoid arthritis for a longer time than men. In women there were more frequent cases of rheumatoid arthritis in the family. In the group of men there were more patients smoking cigarettes and among the smokers they smoked more than women. Women more often realized preventive procedures such as: regular taking medicines, gymnastics and healthy diet. CONCLUSIONS: The condition of knowledge of women on their own disease is definitely higher and relatively high. It was revealed that the interest in obtaining information on the disease is higher in people with higher education both in women and men. Independently of the age, the main source of knowledge on the disease is a doctor, physiotherapist or a nurse. Educational deficiency in therapeutic teams was revealed, which indicates the necessity of developing information programmes and of running trainings, talks aiming at increasing knowledge on rheumatoid arthritis among patients.
22401568 Application of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in Kore 2012 May OBJECTIVE: The aim of this study was to determine how many patients with undifferentiated arthritis (UA) are classified as patients with rheumatoid arthritis (RA) by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA. METHODS: The 2010 ACR/EULAR criteria for RA were applied to 102 patients with UA. UA is defined as an inflammatory arthritis that does not meet any criteria for a definitive diagnosis. We analysed discrepancy in the classification between previous criteria and the 2010 criteria by identifying patients who were categorized as those with RA. RESULTS: The mean age of the patients was 46.8 ± 14.3 years. Rheumatoid factor (RF) was positive in 36 patients (35.2%), and 30 patients (29.5%) were positive for anti-cyclic citrullinated peptide antibody (anti-CCP). The 2010 ACR/EULAR criteria classified 33 patients (32.4%) as having RA, and 31 of them (93.9%) had the involvement of 1-3 small joints. All patients were seropositive, and 25 of them (75.8%) had high positive RF or anti-CCP. Seropositivity and small joint involvement was significantly different between patients who were classified with RA and those who were not (p < 0.001). CONCLUSION: Using the 2010 ACR/EULAR criteria, 32.4% of patients with UA were classified as having RA, and all were seropositive. Most of the UA patients with high positive RF or anti-CCP could be classified as having RA when we applied the 2010 ACR/EULAR criteria.
22211313 Should rheumatoid factor in rheumatoid arthritis be sent to Davy Jones's Locker? 2012 Mar This article reviews the characteristics and weaknesses of the rheumatoid factor (RF) assay compared with anti-citrullinated peptide antibody (ACPA) testing in the work-up of patients with synovitis. This should lead physicians to change their ordering habits and replace RF by ACPA. For RA diagnosis, good clinical judgement based on clinical history, physical examination and routine laboratory work exceeds the value of RF and ACPA assays. In settings of both low and high pretest probability, the added value of each of these assays is low. In cases with intermediate probability, ACPA assays are superior to immunoglobulin (Ig)M-RF because of their higher specificity, and they should be the first choice in a RA diagnostic work-up. Dual testing brings few additional advantages and increases costs significantly. ACPA and IgM-RF are both imperfect tests; around 30% of patients with manifest RA will test negative in both assays and therefore caution needs to be exercised when interpreting negative results. Since 2009, the anti-cyclic citrullinated peptide (anti-CCP) antibody assay has been the only assay available at our institution for RA work-up, with IgM-RF available on a case-by-case basis for non-RA diseases. This has led to a 70% reduction in RF assays performed annually.
22042634 Fatal Histoplasma capsulatum mitral endocarditis in a French patient treated for rheumatoi 2012 Mar Histoplasmosis is an infectious disease caused by the inhalation of Histoplasma capsulatum spores, a fungus encountered in many diverse areas around the world. Although this infection is often asymptomatic, it may become dramatic in immunocompromised patients. In November 2005, an endocarditis due to Histoplasma capsulatum was diagnosed in a French woman treated for rheumatoid arthritis and who had traveled to South America 2 years earlier. We confirmed the biological diagnosis by mycological, serological, and histological methods. In spite of receiving the appropriate treatment, the patient died 3 months later of cardiac insufficiency. We report here this additional case of Histoplasma endocarditis, by hoping to help rapid and accurate diagnosis of such infections in their early stages of development, in non-endemic areas.
22647791 [Treatment of rheumatoid swan neck deformity by tenodesis of proximal interphalangeal join 2012 Jun OBJECTIVES: Surgical treatment of finger swan neck deformities is versatile. We aimed to assess the outcome of PIP tenodesis on unfixed deformities, in patients suffering from rheumatoid arthritis. METHODS: Twenty-three PIP tenodeses were performed on eight patients, using half of a superficialis flexor digitorum tendon sutured to A2 pulley through a volar approach. Postoperative splinting, in 20° of PIP flexion, was maintained for 4 weeks. The patients were assessed retrospectively, at a mean period of 61 months. RESULTS: The PIP flexion gained 26°. On the other hand, a 4°-flexion contraction was induced. The mean postoperative flexion reached 65°. The PIP hyperextension was corrected by 33°. In one same patient, the correction was insufficient for the four fingers. The DIP lack of extension was totally corrected in 70% of the cases and partially in 30%. Each patient had functional improvement. Nineteen good and excellent, and four fair results were reported. No major complication was observed. CONCLUSION: This tenodesis seems to be reliable and to give good long-term results. It is our intervention of choice for rheumatoid flexible swan-neck deformity.
21980439 A systems genetics approach provides a bridge from discovered genetic variants to biologic 2011 Genome-wide association studies (GWAS) have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA). Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC) for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR) algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA-like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: "leukocyte activation and differentiation", "pattern-recognition receptor signaling pathway", and "chemokines and their receptors".These results suggest that the systems genetics approach is useful to find directions of future mapping strategies to illuminate biological pathways.
22930108 [Nervous system side effects of disease modifying treatments of rheumatoid arthritis]. 2012 Sep Antirheumatic medication is of crucial importance within the treatment concept of chronic inflammatory disorders. Side effects may affect various organ systems, among which are neurologic manifestations. If patients have comorbidities involving the nervous system this should be taken into consideration before choosing an individual immunosuppressant or immunomodulatory compound, as any worsening of the underlying neurologic disease should be avoided. In this article, relevant neurologic disorders will be described with respect to the clinical manifestations, differential diagnosis and treatment. In the second part, pharmaceuticals and biologicals which are frequently used as part of an antirheumatic regimen are discussed with respect to the potential to induce side effects specifically related to the nervous system.
21243496 Thrombocytosis in rheumatoid arthritis: JAK2V617F-positive essential thrombocythemia. 2012 Jan Thrombocytosis is an important laboratory finding in rheumatoid arthritis (RA) and it has a correlation with disease activity. Janus kinase 2 valin 617 phenylalanine (JAK2V617F) mutation has gained importance in the diagnosis of myeloproliferative diseases recently. There is no published report in literature on the association between RA and JAK2V617F-positive essential thrombocythemia (ET). In this report, we present a JAK2V617F-positive ET case that had RA. A 57-year-old male patient was diagnosed with RA according to the criteria of American College of Rheumatology (ACR), whose complaint was of pain in the hands and morning stiffness lasting for about 2 h. The patient was evaluated for thrombocytosis because he was in remission and suffering persistent thrombocytosis under treatment. After excluding the causes of secondary thrombocytosis, bone marrow aspiration and biopsy was performed. On peripheral blood and bone marrow PCR examination, the patient was detected to be JAK2V617F positive heterozygously and diagnosed with ET. As a conclusion, mild-moderate thrombocytosis is frequent in RA; however, ET can be diagnosed by JAK2V617F evaluation in peripheral blood in thrombocytosis, especially when platelet count is more than 1 million/ml and when persisting thrombocytosis is detected in RA remission.
22491018 Genome-wide association analysis implicates the involvement of eight loci with response to 2013 Jun Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease affecting the joints. A heterogeneous response to available therapies demonstrates the need to identify those patients likely to benefit from a particular therapy. Our objective was to identify genetic factors associated with response to tocilizumab, a humanized monoclonal antibody targeting the interleukin (IL)-6 receptor, recently approved for treating RA. We report the first genome-wide association study on the response to tocilizumab in 1683 subjects with RA from six clinical studies. Putative associations were identified with eight loci, previously unrecognized as linked to the IL-6 pathway or associated with RA risk. This study suggests that it is unlikely that a major genetic determinant of response exists, and it illustrates the complexity of performing genome-wide association scans in clinical trials.
22457007 Baseline anti-citrullinated peptide antibody (ACPA) titers and serum interleukin-6 (IL-6) 2013 Feb A prospective study was made to seek for a convenient biomarker to predict progression of bone destruction (PBD) in early stages of rheumatoid arthritis (ERA). All participated patients had definite RA and their radiographic stages were mild less than stage II of the Steinbrocker classification, naïve for treatment of any DMARDs or corticosteroids. After the entry, they were treated according to the 2002 ACR management guideline for RA. The candidate biomarkers (RF-IgM, RF-IgG, CARF, ACPA, CRP, ESR, NTx, MMP-3, IL-6 and osteopontin) were measured at the entry. PBD was assessed radiographically by interval changes in the modified Sharp scores (ΔSHS) for 24 months. The associations between ΔSHS and baseline biomarkers were assessed statistically by multivariate regression analyses. Both the baseline ACPA and IL-6 levels correlated with PBD, suggesting that they could predict PBD in ERA.
22057144 Assessment of hand functions in rheumatoid arthritis using SF-SACRAH (short form score for 2012 Nov Rheumatoid arthritis activity is generally evaluated by using DAS-28 score. But this does not reflect the extent of functional hand impairment, a decisive parameter for patient wellbeing as well as for work disability. Several questionnaires to quantify the hand involvement in RA have been elaborated, amongst which SACRAH has been popular since 2003. But this requires evaluating 23 questions on a visual analogue scale. The questions were reduced to 12 in modified-SACRAH (M-SACRAH) and to only five questions in short form SACRAH (SF-SACRAH) so as to make it easily applicable in daily clinical practice. A study was planned to compare M-SACRAH (already validated) to SF-SACRAH in Indian population as no Indian data are available on the same. A total of 100 patients of RA were evaluated for disease activity using DAS-28 score and hand functions using M-SACRAH and SF-SACRAH. The M-SACRAH and SF-SACRAH were then compared based on DAS-28 scores; also M-SACRAH was compared to SF-SACRAH using Spearman's correlation coefficient. The mean value of DAS-28 score was 3.15 ± 0.86. The mean value of SF-SACRAH was 8.065 ± 7.44, and mean value of M-SACRAH was 201.7 ± 201.1008. The correlation of DAS-28 score to SF-SACRAH and M-SACRAH was significant in moderate and high disease activity but insignificant in remission and low disease activity state. The correlation between M-SACRAH and SF-SACRAH showed a spearman's coefficient of 0.998 with a P value of <0.001 (significant correlation). Correlation was significant for all disease activity states and for remission. The study suggests that the disease activity of rheumatoid arthritis (as assessed by DAS-28 score) has a poor correlation with hand functions (as assessed by M-SACRAH and SF-SACRAH) especially in low disease activity and remission states. Further, M-SACRAH and SF-SACRAH are significantly correlated. Therefore, it is suggested that RA patients should be assessed by SF-SACRAH (which includes five questions only) in addition to DAS-28 scoring for better evaluation of hand functions, a detrimental factor in day to day performance of RA patients.
23094810 [Drug compliance - a pitfall of therapy of rheumatoid arthritis?]. 2012 Sep Drug compliance is one of the conditions for effective treatment of various chronic diseases, including rheumatoid arthritis as well. This disease is characterized by a variable course, remissions and relapses, and also by specific treatment. The character of this illness and used medications may represent a risk in terms of non-compliance. As in other chronic diseases, scientists engage in identifying of the compliance rate for many years and the aim of this work is to summarize the state of knowledge in the field of drug compliance in rheumatoid arthritis.
21887490 Rheumatoid arthritis in Burkina Faso: clinical and serological profiles. 2011 Dec The objective of this work was to study the clinical and serological profiles of rheumatoid arthritis in Burkina Faso (West Africa). It is a cross-sectional study conducted from March 2006 to February 2009 in the Internal Medicine Department of the University Hospital Yalgado Ouedraogo. All patients seen in the rheumatologic consultation unit during this period, with rheumatoid arthritis fulfilling the ACR criteria, were routinely selected. The determination of anticyclic citrullinated peptide antibodies (ACPA) was carried out with a computerized method (Elia CCP, Phadia AB, Uppsala, Sweden). Values higher than 10 IU/l were considered positive. Forty-eight cases of rheumatoid arthritis (RA) were recruited throughout the study period among 2,194 (2.2 %) patients. Forty-two files were subjected to the study. There were 34 women and 8 men. The average age was 41.70 ± 13 years with extremes of 22 and 71 years. The average duration of the disease was 86.17 ± 82.01 months with extremes of 8 and 360 months. Rheumatoid factors (RF) were positive in 21 out of 30 patients (70.0%). The determination of ACPA carried out in all the patients was positive in 34 (81%) patients; their average value was 217 IU/l with extremes of 38 and 1,170. RF and ACPA were associated to bones erosions (p = 0.0001). Twenty-two patients were placed on methotrexate, eight on hydroxychloroquine, and three on salazopyrine. Nine were given only NSAIDs or prednisolone. No patients had had a biotherapy agent. The frequency of RA was low in our study compared to other African studies published so far. The particularity of RA cases reported in African series, including ours, is the rarity of extra-articular manifestations of the disease. The severity of the disease at presentation in the rheumatology clinic may be due to their late consultation among other causes.
23007741 Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. 2012 Nov Bone erosion is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome. Erosion of periarticular cortical bone, the typical feature observed on plain radiographs in patients with rheumatoid arthritis, results from excessive local bone resorption and inadequate bone formation. The main triggers of articular bone erosion are synovitis, including the production of proinflammatory cytokines and receptor activator of nuclear factor κB ligand (RANKL), as well as antibodies directed against citrullinated proteins. Indeed, both cytokines and autoantibodies stimulate the differentiation of bone-resorbing osteoclasts, thereby stimulating local bone resorption. Although current antirheumatic therapy inhibits both bone erosion and inflammation, repair of existing bone lesions, albeit physiologically feasible, occurs rarely. Lack of repair is due, at least in part, to active suppression of bone formation by proinflammatory cytokines. This Review summarizes the substantial progress that has been made in understanding the pathophysiology of bone erosions and discusses the improvements in the diagnosis, monitoring and treatment of such lesions.
22586162 Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arth 2013 Mar INTRODUCTION: Interleukin-6 receptor (IL-6R) blockade improves the signs and symptoms of rheumatoid arthritis (RA) and retards bone damage. Whether IL-6R blockade allows repair of existing bone erosions is so far unclear. METHODS: This study examined bone erosions in the metacarpophalangeal joints of 20 patients receiving treatment with the IL-6R blocker tocilizumab using micro CT (µCT). The maximal width and depth of individual bone erosions was measured at baseline and after 1 year of treatment. RESULTS: 133 bone erosions were identified at baseline with a mean (±SD) size of 2.23±1.26 mm and depth of 2.16±1.50 mm. Distribution analysis showed predominant involvement of the second compared with the third and fourth metacarpophalangeal joints, the metacarpal heads compared with the phalangeal bases and the radial quadrants compared with all other surfaces. Repair of bone erosions during tocilizumab treatment was confined to those lesions showing sclerosis at baseline and/or at follow-up and those with a width larger than 1.6 mm. The mean decrease in width of sclerosed erosions was thus 0.14±0.05 mm (p=0.0086) and 0.20±0.08 mm (p=0.019) for sclerosing lesions after 1 year of treatment. CONCLUSIONS: Blockade of IL-6R by tocilizumab can induce limited repair in a subset of erosions, particularly in large lesions with sclerosis. Repair of erosions during tocilizumab treatment reflects the favourable impact of IL-6R blockade on local bone remodelling in patients with RA.
22004369 Social support and psychological distress in rheumatoid arthritis: a 4-year prospective st 2012 INTRODUCTION: The objective of the study was to investigate the course of psychological distress in early rheumatoid arthritis patients and to explore the strength of its associations with disease-related variables over time. A further aim focused specifically on the associations between social support and psychological distress. METHODS: The study had a longitudinal design, with four annual measurements over consecutive years. The course and stability of psychological distress on the individual level were investigated via test-retest correlation coefficients and changes over time were studied using the Friedman test for repeated measurements. Hierarchical regression analysis was performed to analyze the multilinear associations of disease activity, functional disability, joint tenderness, pain and social support with psychological distress. RESULTS: Significant cross-sectional associations were found among functional disability, joint tenderness, pain, emotional support, instrumental support and psychological distress. However, after controlling for the erratic pattern of the disease and the relevant variables, only initial psychological distress and emotional support retained a significant relationship with psychological distress. The final regression model, in which functional disability, pain, emotional support and initial psychological distress were significant variables, explained 36% of the variance in psychological distress. CONCLUSION: The study stresses the importance of initial psychological distress, which was found to have the highest correlation with psychological distress experienced 4 years later. In addition, higher emotional support and lower pain were found to be the only variables independently associated with lower levels of psychological distress after controlling for the relevant variables.
22548958 NPSR1 gene is associated with reduced risk of rheumatoid arthritis. 2012 Jun OBJECTIVE: Neuropeptide S receptor 1 (NPSR1) is a G protein-coupled receptor involved in immune response and is associated with several inflammatory diseases. We investigated the possible contribution of several polymorphisms in the intronic region of NPSR1 to rheumatoid arthritis (RA). METHODS: Genotyping of 7 single-nucleotide polymorphisms (SNP) was performed in a total of 1232 patients with RA and 983 healthy controls of Spanish white origin by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. RESULTS: One out of the 7 SNP analyzed (rs740347) was associated with RA [p after Bonferroni correction (p(BNF)) = 1.2 × 10(-3), OR 0.73]. An association was also observed with rheumatoid factor-positive and shared epitope-positive RA (p(BNF) = 0.011, OR 0.73; p(BNF) = 0.037, OR 0.75, respectively). CONCLUSION: Our results show that variations in the NPSR1 intronic region are associated with low risk in patients with RA, supporting other evidence that this locus represents a common genetic factor in inflammatory diseases.
22895876 Rheumatoid arthritis in Senegal: a comparison between patients coming from rural and urban 2012 Nov Several studies have suggested that rheumatoid arthritis (RA) is uncommon in rural sub-Saharan Africa. The aim of this study is to determine the potential differences between patients with RA living in rural areas and those living in urban areas. We performed a cross-sectional study from June 2006 to May 2009. We included all patients with RA (1987 ACR criteria) seen at the Rheumatology Unit of the Le Dantec Teaching Hospital, Dakar, Senegal. We compared the main socio-demographic and clinical characteristics of patients living in rural areas to those living in urban areas. We included 180 patients in our study, of whom, 143 (79.4 %) lived in urban areas and 37 (20.6 %) in rural areas. The median age was 44 years [range 34-55] in patients from rural areas vs. 41 years [range 30-53] in patients from urban areas, without any statistical significance (p = 0.24). Patients under the age of 60 mostly lived in urban areas (p = 0.03). The extra-articular manifestations were significantly more frequent in patients living in rural areas (p = 0.02). There was no statistical significance when comparing the delay in diagnosis, number of swollen joints, disease activity, hand deformities, and concentration of autoantibodies (RF and ACPA) in both populations. The percentage of patients seen from the rural areas of Senegal is low (20.6 %) compared to those seen from the urban areas. The number of extra-articular manifestations is the main difference between patients living in rural and urban areas. The role played by environmental factors seems important. Further incidence studies are needed.
20961791 Cell and cytokine imbalances in rheumatoid synovitis. 2011 May Rheumatoid synovitis is a complex process in which systemic and local homeostatic dysregulation is expressed in the joint. The main genetic susceptibility factors are HLA-DRB1 alleles containing the shared epitope. Environmental factors predominate over genetic factors in the pathogenesis of rheumatoid arthritis (RA), and among them smoking is the most powerful. In RA, disruptions in self-tolerance lead to abnormalities such as recognition of citrullinated antigens by B and T cells. The balance of lymphocyte differentiation in RA is skewed toward the Th1 phenotype, to the detriment of the Th2, Th17, and T regulator (Treg) phenotypes. Imbalances occur in the main cytokine systems including IL-1, TNF, IL-6, IL-18, IL-15, IL-33, IL-22, and IL-13. The joint destruction seen in RA is caused not only by these cytokine imbalances, but also by specific effects of the Wnt system and osteoprotegerin on osteoclasts and by matrix production dysregulation responsible for cartilage damage.