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ID PMID Title PublicationDate abstract
23116710 Mast cells and inflammation. 2013 Mar The prominent role for mast cells in the inflammatory response has been increasingly well documented in recent years. Mast cells not only contribute to maintain homeostasis via degranulation and to generate IgE-mediated allergic reactions, but also sit at a major crossroads for both innate and adaptive immune responses. The part played by mast cells in chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis identifies mast cells as a valuable treatment target in these diseases. Tyrosine-kinase inhibitors targeting the c-Kit mast cell receptor have been found effective in treating rheumatoid arthritis, asthma, and multiple sclerosis. When used in combination with other available drugs, tyrosine-kinase inhibitors may improve the therapeutic management of these diseases.
22878378 Characteristics of idiopathic atlanto-axial subluxation: a comparative radiographic study 2013 Jan OBJECTIVE: Atlanto-axial subluxation (AAS) is caused by multiple conditions; however, idiopathic AAS patients without RA, upper-cervical spine anomalies or any other disorder are rarely encountered. This study retrospectively investigated the radiographic findings in idiopathic AAS patients, and clarified the differences between those AAS patients and those due to RA. METHODS: Fifty-three patients with AAS treated by transarticular screw fixation were reviewed. The subjects included 8 idiopathic patients (ID group) and 45 RA patients (RA group). The study investigated the atlanto-dental interval (ADI) value and space available for spinal cord (SAC) at the neutral and maximal flexion position. RESULTS: The average ADI value at the neutral position in the ID and RA groups before surgery was 7.8 and 7.2 mm, respectively (p > 0.74). The average ADI value at the flexion position in the two groups was 10.3 and 11.7 mm, respectively (p > 0.06). The average SAC value at the neutral position in the two groups was 12.0 and 17.1 mm, respectively (p < 0.01). Finally, the average SAC value at the flexion position in the two groups was 10.7 and 13.5 mm, respectively (p < 0.01). CONCLUSIONS: The SAC value at both the neutral and flexion positions in idiopathic AAS patients was significantly smaller than those values in RA-AAS patients. This may be because the narrowing of the SAC in the idiopathic group easily induces cervical myelopathy. Furthermore, surgery was often recommended to RA patients, because of the neck pain induced by RA-related inflammation of the atlanto-axial joint, regardless of any underlying myelopathy.
22627728 Reliability testing of tendon disease using two different scanning methods in patients wit 2012 Sep OBJECTIVE: To assess the intra- and interobserver reliability of musculoskeletal ultrasonography (US) in detecting inflammatory and destructive tendon abnormalities in patients with RA using two different scanning methods. METHODS: Thirteen observers examined nine patients with RA and one healthy individual in two rounds independently and blindly of each other. Each round consisted of two consecutive examinations, an anatomy-based examination and a free examination according to personal preferences. The following tendons were evaluated: wrist extensor compartments 2, 4 and 6, finger flexor tendons 3 and 4 at MCP level, tibialis posterior tendon and both peronei tendons. Overall, positive and negative agreements and κ-values for greyscale (GS) tenosynovitis, peritendinous power Doppler (PPD) signal, intratendinous power Doppler (IPD) signal and GS tendon damage were calculated. RESULTS: Intraobserver κ-value ranges were 0.53-0.55 (P < 0.0005) for GS tenosynovitis, 0.61-0.64 (P < 0.0005) for PPD signal, 0.65-0.66 (P < 0.0005) for IPD signal and 0.44-0.53 (P < 0.0005) for GS tendon damage. For interobserver reliability, substantial overall agreement ranged from 80 to 89% for GS tenosynovitis, 97 to 100% for PPD signal, 97 to 100% for IPD signal and 97 to 100% for GS tendon damage. Results were independent of scanning technique. CONCLUSION: Intraobserver reliability for tenosynovitis and tendon damage varied from moderate for GS to good for PD. Overall interobserver reliability for tenosynovitis and tendon damage was excellent both for GS and PD. This qualitative scoring system may serve as the first step to a semi-quantitative score for tendon pathology.
21956233 Is DAS28-CRP with three and four variables interchangeable in individual patients selected 2011 Dec DAS28 is a widely used composite score for the assessment of disease activity in patients with rheumatoid arthritis (RA) and is often used as a treatment decision tool in the daily clinic. Different versions of DAS28 are available. DAS28-CRP(3) is calculated based on three variables: swollen and tender joint counts and CRP. DAS28-CRP(4) also includes patient global assessment. Thresholds for low and high disease activity are the same for the two scores. Based on the Bland-Altman method, the interchangeability between DAS28-CRP with three and four variables was examined in 319 RA patients selected for initiating biological treatment. Data were extracted from the Danish registry for biological treatment in rheumatology (DANBIO). Multiple regression analysis was used to assess the predictability of the DAS28 scores by several measures of disease activity. The overall mean DAS28-CRP was 4.7 ± 1.2. The mean difference between the two scores (the bias) was -0.29 ± 0.33 (CI -0.33, -0.25) (p < 0.0001). Upper and lower limits of agreement were -0.95 (CI -1.01, -0.89) and 0.37 (CI 0.31, 0.43), respectively. Tender joint count was the most important predictor of both DAS28-CRP(4) (beta = 0.52, p < 0.0001) and DAS28-CRP(3) (beta = 0.62, p < 0.0001). The second most important predictor of DAS28-CRP(4) was patient global assessment (beta = 0.32, p < 0.0001) which did not add to the prediction of DAS28-CRP(3). In conclusion, overall DAS28-CRP(3) was only slightly underestimated compared to DAS28-CRP(4). In the individual patient, however, the two scores may differ considerably. The scores should not be used interchangeably in the daily clinic without caution.
21954166 Relationship between accelerometer-based measures of physical activity and the Yale Physic 2011 Dec OBJECTIVE: To evaluate the correlation between the Yale Physical Activity Survey (YPAS) scores and objective accelerometer measures of time spent in light intensity physical activities, moderate to vigorous intensity physical activities, and moderate to vigorous activities in bouts lasting at least 10 minutes. METHODS: This study analyzed baseline data from 171 persons with rheumatoid arthritis (RA) and 139 persons with osteoarthritis (OA) in a randomized clinical trial (Increasing Motivation for Physical Activity in Arthritis Clinical Trial). Persons fulfilling the 1987 American College of Rheumatology criteria for RA and persons with symptomatic radiologic knee OA (Kellgren/Lawrence class ≥2) wore an accelerometer for 7 days, then responded to the YPAS questionnaire and questions regarding demographics (age, sex, and race) and health factors (body mass index, disease status [Health Assessment Questionnaire/Western Ontario and McMaster Universities Osteoarthritis Index], comorbidities, pain, and function). Spearman's correlation coefficients were estimated between each YPAS summary measure and accelerometer measures. RESULTS: In the RA participants, the strongest correlation was between the YPAS activity dimensions summary index (Y-ADSI) and average daily minutes of bouted moderate/vigorous activity (r = 0.51). Additionally, the Y-ADSI correlated significantly with both objectively measured average daily accelerometer counts (r = 0.45) and average daily minutes of moderate/vigorous activity (r = 0.43). For OA participants, a similar pattern emerged: the Y-ADSI had significant correlations with average daily minutes of bouted moderate/vigorous activity (r = 0.36), average daily minutes of moderate/vigorous activity (r = 0.31), and average daily counts (r = 0.24). CONCLUSION: For both the RA and OA groups, the Y-ADSI had the strongest significant correlations with objectively measured physical activity, which supports Y-ADSI use as a tool for clinical applications and in rheumatology research.
21292734 28-Joint count disease activity score at 3 months after diagnosis of early rheumatoid arth 2011 Jul OBJECTIVE: To explore possible association between disease activity at 3-month follow-up after RA diagnosis and costs over the following 4 years. METHODS: Three-hundred and twenty patients with early (≤ 1 year) RA were assessed at regular intervals. Clinical and laboratory data were collected and patients reported health-care utilization and number of days lost from work. At 3-month follow-up, patients were divided into two groups according to disease activity, using DAS-28 with a cut-off level at 3.2. Direct and indirect costs and EuroQol-5D over the following 4 years were compared between the groups. Multivariate regression models were used to control for possible covariates. RESULTS: Three months after diagnosis, a DAS-28 level of ≥ 3.2 was associated with high direct and indirect costs over the following 4 years. Patients with DAS-28 ≥ 3.2 at 3-month follow-up had more visits to physician, physiotherapist, occupational therapist and nurse, higher drug costs, more days in hospital and more extensive surgery compared with patients with 3-month DAS-28 < 3.2. Number of days lost from work due to sick leave and permanent work disability was also higher in this group. The effect of disease activity on health-related quality of life was highly significant. In regression models, DAS-28 at 3-month follow-up was significantly associated with costs over the following years. CONCLUSIONS: Three months after diagnosis, DAS-28 is an important prognostic marker regarding health-care utilization and costs. Achieving remission or low disease activity 3 months after diagnosis is likely to decrease morbidity, increase quality of life and save costs for the patient and for society over the following years.
22373834 Tocilizumab has no clinically relevant effects on methotrexate pharmacokinetics in patient 2012 Mar OBJECTIVE: To assess the effects of tocilizumab on methotrexate and 7-hydroxymethotrexate pharmacokinetics in patients with rheumatoid arthritis and to explore the pharmacodynamic effect of tocilizumab on C-reactive protein (CRP), a marker of inflammation. METHODS: Methotrexate (10 - 25 mg) was administered orally on Days 1, 8, 15, 22, 29, 36, and 43. On Day 8 patients received 10 mg/kg tocilizumab intravenously. Blood samples for pharmacokinetic analyses were collected on Days 1, 15, and 43 and for pharmacodynamics (CRP) throughout the study. RESULTS: 90% CIs for mean effect ratios (Day 15/Day 1 and Day 43/Day 1) of methotrexate and 7-hydroxymethotrexate (AUClast and Cmax) were close to or within the bioequivalence boundaries (80 - 125%). CRP normalized within 1 week after tocilizumab injection and remained within normal limits for 3 weeks. CONCLUSION: Tocilizumab and methotrexate can be administered concurrently without dosage adjustments.
21800113 Should anti-TNF therapy be discontinued in rheumatoid arthritis patients undergoing electi 2012 Jan Anti-tumour necrosis factor (TNF) therapies have revolutionized the management of rheumatoid arthritis (RA). A high proportion of RA patients are now established users of anti-TNF agents. Unfortunately, many RA patients with longstanding disease still require elective orthopaedic procedures. Published studies on the influence of TNF antagonist on infection rates in RA patients undergoing surgery are conflicting. However, national registries of RA patients on anti-TNF reported an increased risk of infection. The risk of anti-TNF-related infection is highest at the start of treatment with frequent involvement of the skin and subcutaneous tissue. Infection at these sites could negatively influence the healing of surgical wound. Current guidelines suggest that treatment with biologics should be discontinued prior to surgery. Patients with established disease are more likely to flare compared to those with early disease on stopping treatment. Consequently, TNF blockers need to be reinstated promptly after surgery to avoid the risk of RA flare.
21738080 Association of Cullin1 haplotype variants with rheumatoid arthritis and response to methot 2011 Sep Aberrations in ubiquitin pathway have been implicated in many diseases and drug response. In a previous study on rheumatoid arthritis (RA) in Japanese population, significant association of Cullin1 gene (CUL1), an ubiquitin E3 ligase, was observed. CUL1 also mediates degradation of IκBα and p27, levels of which has been associated with RA etiology and drug response, respectively. We carried out a replication study of association of CUL1 polymorphisms with RA in a north Indian population. Allelic, genotypic, and haplotypic associations of a promoter and two intronic polymorphisms of CUL1 with RA and with methotrexate response in patients with RA, were tested. A significant association (P=0.00056, adjusted) of a haplotype A-T-T with RA (odds ratio=3.68; 95% confidence interval=1.86-7.27) and in patients with RA poorly responding to methotrexate treatment (P=0.04, adjusted) was observed. Association with CUL1 haplotype indicates a possible role of CUL1 variation(s) in RA and its response to methotrexate.
20806274 Quality care in seniors with new-onset rheumatoid arthritis: a Canadian perspective. 2011 Jan OBJECTIVE: To estimate the percentage of seniors with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) within the first year of diagnosis. METHODS: We assembled an incident RA cohort from Ontario physician billing data for 1997-2006. We used a standard algorithm to identify 24,942 seniors with RA based on ≥ 2 billing codes ≥ 60 days apart but within 5 years. Drug exposures were obtained from pharmacy claims data. We followed subjects for 1 year, assessing if they had been exposed (defined as ≥ 1 prescription) to 1 or more DMARDs within the first year of RA diagnosis. We assessed secular trends and differences for subjects who had received rheumatology care (defined as ≥ 1 rheumatology encounter) versus those who had not. RESULTS: In total, only 39% of the 24,942 seniors with new-onset RA identified over 1997-2006 were exposed to DMARD therapy within 1 year of diagnosis. This increased from 30% in 1997 to 53% in 2006. Patients whose care involved a rheumatologist were more likely to be exposed to DMARDs than those who had no rheumatology care. In 2006, 67% of subjects receiving rheumatology care were exposed to DMARDs versus 21% of those with no rheumatology care. CONCLUSION: Improvements in RA care have occurred, but more efforts are needed. Subjects receiving rheumatology care are much more likely to receive DMARDs as compared to those with no rheumatology care. This emphasizes the key role of rheumatologists.
22089467 Proposed severity and response criteria for Routine Assessment of Patient Index Data (RAPI 2011 Dec BACKGROUND: An index is needed to assess the status of patients with rheumatoid arthritis (RA), as none of the existing measures are applicable to all individual patients. The 28-joint Disease Activity Score (DAS28) is the most specific and widely used index. Routine Assessment of Patient Index Data (RAPID3) is an index containing only the 3 patient self-report core dataset measures, without a laboratory test or formal joint count, and with simple scoring. RAPID3 is correlated significantly with DAS28, but calculated in 5-10 seconds on a Multidimensional Health Assessment Questionnaire (MDHAQ), compared to 114 seconds for DAS28. METHODS: DAS28 (0-10 scale) categories for high, moderate, and low activity, and remission (≤ 2.6, 2.6-3.2, 3.21-5.1, and > 5.1, respectively) and proposed RAPID3 (0-30 scale) categories for severity (0 ≤ 3, 3.1-6, 6.1-12, and > 12) were compared in patients taking abatacept and control-treated patients at the endpoint of the Abatacept in Inadequate Response to Methotrexate (AIM) and the Abatacept Trial in Treatment of Anti-TNF INadequate Responders (ATTAIN) clinical trials, using cross-tabulations and kappa statistics. RESULTS: Overall, 92%-99% of patients classified as having high DAS28 activity had high or moderate RAPID3 severity, while 64%-83% in DAS28 remission had RAPID3 low severity or remission; 50%-82% of patients with good or poor EULAR responses had good or poor RAPID3 responses. Kappa values ranged from 0.25 to 0.48, and weighted kappas from 0.32 to 0.52, indicating fair to moderate agreement for the 2 indices. CONCLUSION: Proposed RAPID3 severity and response categories yield comparable results to DAS28 and EULAR criteria in AIM and ATTAIN. DAS28 is more specific for clinical trials. RAPID3 does not preclude also scoring DAS28, and may be informative in the infrastructure of routine care.
22270725 Leflunomide-induced pulmonary hypertension in a young woman with rheumatoid arthritis: a c 2012 Jun Leflunomide, a disease-modifying antirheumatic drug, has been shown to be effective in the management of rheumatoid arthritis (RA). Among other side effects, systemic hypertension has been described, and also a case of possible pulmonary hypertension (PH) has been reported. Symptomatic PH in RA is rare. We present a 28-year-old woman with a history of RA who consulted our hospital because of severe symptomatic pulmonary hypertension. Two years before admission, she was started on leflunomide. Due to previous evidence of the association of leflunomide with pulmonary hypertension, the drug was stopped. The patient became asymptomatic with normal pulmonary arterial pressure within a year. Given the poor prognosis of idiopathic pulmonary arterial hypertension, the recognition of potentially reversible causes is crucial. Until further evidence is available in a patient who develops pulmonary arterial hypertension, stopping leflunomide should be considered.
20929971 Health-related quality of life and continuation rate on first-line anti-tumour necrosis fa 2011 Jan OBJECTIVES: To describe changes in health-related quality of life (HRQoL) up to 60 months after commencing anti-TNF therapy for RA patients enrolled in the Australian Rheumatology Association Database (ARAD), and to determine the continuation rate and predictors of discontinuation of first-line anti-TNF therapy. METHODS: Responses to the HAQ, Assessment of Quality of Life, Medical Outcomes Study Short Form-36 (SF-36) and European Quality of Life-5 Dimensions (EQ-5D) were extracted from ARAD for patients commencing anti-TNF therapy and analysed in 6-monthly intervals from the start date. Predictors of discontinuation of therapy were assessed using Cox regression. RESULTS: Since September 2001, 2601 RA patients have enrolled in ARAD; 1801 have used anti-TNF therapy. Before starting the therapy, all HRQoL scores were below the population norms, but showed improvements in the first 6 months. From 12 to 60 months, HRQoL remained stable but below population means. Data to 60 months were available for 106 patients; 47% were still on first-line therapy at 5 years, all were using concurrent DMARDs and 55% were using concurrent prednisolone. Predictors of discontinuation of therapy were poorer HRQoL scores, a more recent therapy start date, concurrent prednisolone use and self-reported severe infection. Older patients and those with longer symptom duration were more likely to remain on therapy. CONCLUSIONS: In routine practice, HRQoL scores improve rapidly within 6 months of starting anti-TNFs and then remain stable for up to 60 months. Almost half remain on first-line therapy.
21350796 The value of early intervention in RA--a window of opportunity. 2011 Mar Rheumatoid arthritis (RA) is associated with progressive joint destruction, with functional status influenced by both disease activity and radiographic progression. The case for early aggressive treatment of RA is based on large amounts of good data in many countries. Studies with conventional disease-modifying anti-rheumatic drugs in early RA have shown improved outcomes compared with later treatment, especially if an aggressive approach with combinations of drugs is used. Early intervention with tumour necrosis factor (TNF) inhibitors has been shown to improve clinical outcomes, induce remission and prevent radiographic progression. It also improves patients' functional status, health-related quality of life, and reduces fatigue. Patients with RA have reduced productivity, an increased number of lost work days and retire early; enabling patients to work should be at the core of a therapy's cost-effectiveness. Introduction of anti-TNF therapy early in RA has been shown to decrease job loss and reduce the amount of working time missed. Although the drug costs of initial treatment with combination therapy including a TNF inhibitor are high, these may be compensated by the reduction in lost productivity, making such a strategy cost-effective overall. In addition, some patients who respond well to combination therapy may be able to stop the TNF inhibitor. It is important to assess the benefits of any intervention not just to healthcare costs but to society as a whole, and physicians should be advocates for optimal access to effective therapies for their patients.
21813056 Assessing the cost-effectiveness of biologic agents for the management of moderate-to-seve 2011 Jul OBJECTIVES: The objective of this study is to assess cost-effectiveness of different biologic strategies in patients with moderate-to-severe active RA after an insufficient response to anti-TNF agents within the context of the Italian healthcare system. METHODS: Simulation models were developed allowing for potential biologic therapy switch at each 6-month time point in case of an insufficient response to the previous biologic agent. Biologic treatments included etanercept, abatacept, adalimumab, rituximab or infliximab. Effectiveness criteria for these models were defined as achieving a state of low disease activity (LDAS) [DAS28 ≤3.2] or remission (RS) [DAS28<2.6]. Monte-Carlo simulations were performed for each sequence to manage data variability. RESULTS: The biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appeared significantly more efficacious over 2 years (102 days in LDAS) compared to rituximab (82 days in LDAS). The sequence using abatacept after 2 anti-TNF agents appeared significantly more efficacious (63 days in LDAS) compared to using a third anti-TNF agent (32 days in LDAS). Mean cost-effectiveness ratios showed significantly lower costs per day in LDAS with abatacept used after one anti-TNF agent (€376) compared to rituximab (€456). The sequence using abatacept after 2 anti-TNF agents was also more cost-effective (€642 per day in LDAS) versus a sequential use of anti-TNF therapies (€1164 per day in LDAS). All comparisons were confirmed when using the remission effectiveness criteria. CONCLUSIONS: The results of this health economics modelling study suggest that the biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appears significantly more effective and cost-effective versus a similar sequence using rituximab for achieving remission or LDAS. The results also indicate that in the case of an insufficient reponse to 2 anti-TNF agents, abatacept appears more effective and cost-effective than using a 3rd anti-TNF agent.
23346247 Clinical particularities and response to the anti-inflammatory effect of antiviral treatme 2012 Dec 15 Hepatitis C virus (HCV) is an important cause for the development of serious hepatic disease such as chronic hepatitis and liver cirrhosis. Though the pathological mechanisms are poorly understood, it is well established that CHC plays an important role in several immune mediated conditions, including rheumatoid arthritis. We focused on the clinical particularities of patients with CHC and associated RS and we specifically investigated the anti-inflammatory role of IFN-alpha concerning the rheumatic symptoms.
21949922 New biologics for rheumatoid arthritis. 2011 Sep Rheumatoid arthritis (RA) is a chronic inflammatory arthritis with many systemic manifestations. Several monoclonal antibodies targeting different components of the immune systems have been licensed for treatment of RA. Inflammatory cytokines such as interleukin-6 (IL-6) are found abundantly in the blood and the joints. The biologic effect of IL-6 on leukocyte, osteoclast, hepatocytes and bone marrow may mediate the articular and systemic inflammation in RA. Recently, an anti-IL-6 receptor monoclonal antibody, tocilizumab, has been licensed for the treatment as monotherapy or in combination with methotrexate of moderate to severe RA, when disease modifying anti-rheumatic drugs or anti-tumour necrosis factors (TNF) have failed. It improves symptoms and signs as well as reducing joint damage. Tocilizumab monotherapy has been shown to be superior to methotrexate. Its side-effects include infections, decrease in neutrophils, and increases in lipid and liver transaminases. Overall, tocilizumab has a well-defined and manageable safety profile that supports a favourable benefit/risk ratio for patients with RA.
21563508 The extraarticular symptoms influence ACR response in the treatment of rheumatoid arthriti 2011 Mar OBJECTIVE: The extraarticular symptoms are important in the pattern differentiation of traditional Chinese medicine (TCM), and the present study is designed in an attempt to find the associations between the extraarticular symptoms and American College of Rheumatology (ACR) Response in 194 cases of rheumatoid arthritis (RA) treated with biomedicine. METHODS: The data were obtained from a randomized clinical trial. One hundred ninety-four RA patients were treated with the biomedical therapy (diclofenec, methotrexate and sulfasalazine). ACR20 response in 24 weeks was used for the efficacy evaluation. Eighteen symptoms (including 13 extraarticular symptoms) that TCM practitioners focus on were collected for exploration on the association between the symptoms and the efficacy of the biomedical therapy with association rules method. RESULTS: After 24 weeks, a total of 135 patients receiving biomedicine had achieved an ACR20 response. The association rules analysis on each symptom showed that soreness in the waist was more associated with ACR20 response, but with lower support (selected sample size based, 20.10% and 14.95% respectively); cold intolerance and cold joint were found to be associated with ACR20 response with higher support (48.97% and 53.61% respectively), and the confidences (predicted effective rate) were 73.08% and 71.23% respectively. The associations between combination of symptoms (among them, there was at least one extraarticular symptom) and ACR20 response indicated that cold intolerance or cold joint with higher confidence and support were the most important extraarticular symptoms. CONCLUSION: The RA patients with "cold intolerance" and "cold joints", which are the extraarticular symptoms that TCM practitioners focus on, may show higher ACR20 response when treated with the biomedical approach.
22587780 Detection of antibodies against synthetic peptides mimicking ureases fragments in sera of 2012 Nov Rheumatoid arthritis (RA) is a chronic disease with an autoimmunological background. RA is mostly characterized by systemic inflammation and injuries of synovial joints. There is a hypothesis that bacterial infections may be connected with development of the disease. It has been suggested that molecular mimicry between bacterial and human antigens may be one of possible mechanisms of RA development. One of potential antigens involved in this mechanism is urease - enzyme with high structural conservatism, occurring in pathogenic and commensal bacteria. We found that the level of antibodies against peptide mimicking urease "flap" region is significantly higher in sera from patients with rheumatoid arthritis in comparison with volunteer blood donor sera. We also observed that antibodies present in RA sera may bind not only specific peptide antigens but also peptides with a slightly different structure.
23007802 CC motif chemokine ligand 13 is associated with rheumatoid arthritis pathogenesis. 2013 Sep OBJECTIVES: CC motif chemokines are considered to be implicated in the pathogenesis of rheumatoid arthritis (RA) via recruitment of monocytes and lymphocytes. CC motif chemokine ligand 13 (CCL13)/monocyte chemoattractant protein-4 (MCP-4) is postulated to be a potent RA inducer. We conducted a study to more precisely clarify the role of CCL13 in RA pathogenesis. METHODS: CCL13 expression was evaluated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining in serum samples and synovial tissues from RA patients. The effects of CCL13 against apoptosis were monitored on cultured synovial fibroblasts. The chemoattractant activity of CCL13 was evaluated by the Boyden chamber assay in monocytes (THP-1 cells) and human umbilical vein endothelial cells (HUVECs). RESULTS: We found that CCL13 serum level and synovial tissue expression were increased in RA patients. CCL13 had chemoattractant activity for both THP-1 cells and HUVECs. Interestingly, CCL13 expression was positively regulated by tumor necrosis factor-alpha (TNF-α). Furthermore, apoptosis induced by hydrogen peroxide (H2O2) and serum deprivation was inhibited by CCL13 on the cultured synovial fibroblasts. CONCLUSIONS: CCL13 may be associated with disease progression as a result of its antiapoptotic effects, increased macrophage infiltration, and synovial tissue angiogenesis in RA patients.