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ID PMID Title PublicationDate abstract
22588476 Newly reported lupus and rheumatoid arthritis in relation to deployment within proximity t 2012 Jun OBJECTIVE: To assess the relationship between possible exposure to smoke from documented open-air burn pits and newly reported lupus and rheumatoid arthritis among Millennium Cohort participants who have deployed in support of operations in Iraq and Afghanistan. METHODS: Prospectively assessed self-reported lupus and rheumatoid arthritis among deployers who completed both 2004-2006 and 2007-2008 questionnaires. RESULTS: After exclusions, more than 18,000 participants were deployed, including more than 3000 participants deployed within a 3-mile radius of a documented burn pit. After adjustment, proximity within 3 miles of a burn pit was not significantly associated with rheumatoid arthritis or lupus in general; however, one location was associated with lupus, although few cases were at this site (n = 2). CONCLUSIONS: Results indicate deployers potentially exposed to documented burn pits in the combined three-camp analysis were not at an elevated risk of lupus or rheumatoid arthritis.
19862529 Recurrent pneumothorax associated with pulmonary nodules after leflunomide therapy in rheu 2011 Jul Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterized by destructive synovitis and systemic extraarticular involvement. One of the most common pulmonary manifestations of RA is rheumatoid nodule. Spontaneous pneumothorax also very rare pulmonary finding and could be associated with pulmonary nodules. Antirheumatic drugs, methotrexate, leflunomide (LEF), infliximab and etanercept, were known as risk factors for developing rheumatoid nodule. However, there was no case report of rheumatoid nodule-associated pneumothorax with the use of LEF. We report, first, herein a case of 46-year-old woman with RA who suffered recurrent spontaneous pneumothorax associated with multiple bilateral subpleural cavitary nodules during treatment with LEF. We reviewed the cases of LEF-related pulmonary nodules developed in patients with RA. Thus, we suggested that pneumothorax can be a rare respiratory fatal complication in patients with RA with pulmonary nodules and LEF can be a rare cause of these manifestations.
22933357 Cortisol-mediated adhesion of synovial fibroblasts is dependent on the degradation of anan 2012 Dec OBJECTIVE: In rheumatoid arthritis (RA) synovial fluid, levels of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol are elevated. Since synovial fibroblasts (SFs) possess all of the enzymes necessary for endocannabinoid synthesis, it is likely that these cells contribute significantly to elevated endocannabinoid levels. While glucocorticoids initiate endocannabinoid synthesis in neurons, this study was undertaken to test whether cortisol also regulates endocannabinoid levels in mesenchymal cells such as SFs, and whether this interferes with integrin-mediated adhesion. METHODS: Adhesion was determined in 1-minute intervals over 60 minutes using an xCELLigence system. Slopes from individual treatment groups were averaged and compared to the control. Fatty acid amide hydrolase (FAAH) and cyclooxygenase 2 (COX-2) were detected by immunocytochemistry, and AEA was detected by mass spectrometry. RESULTS: Cortisol increased the adhesion of RASFs and osteoarthritis SFs with a maximum of 200% at both 10(-7) M and 10(-8) M. When cortisol was administered together with either cannabinoid receptor 1 (CB(1) ) antagonist (rimonabant; 100 nM), CB(2) antagonist (JTE907; 100 nM), transient receptor potential vanilloid channel 1 (TRPV-1) antagonist (capsazepine; 1 μM), FAAH inhibitor, or COX-2 inhibitor, adhesion was reduced below the level in controls. Concomitant inhibition of FAAH and COX-2 reversed these effects. Mass spectrometry revealed the presence of AEA in SFs. CONCLUSION: Our findings indicate that glucocorticoid-induced adhesion is dependent on CB(1) /CB(2) /TRPV-1 activation. Since AEA is produced in SFs, this endocannabinoid is the most likely candidate to mediate these effects. Since AEA levels are regulated by COX-2 and FAAH, inhibition of both enzymes along with low-dose glucocorticoids may provide a therapeutic option to maximally boost the endocannabinoid system in RA, with possible beneficial effects.
23157096 [Anesthetic management of a patient with thrombocytopenia induced by methotrexate undergoi 2012 Oct A 70-year-old woman underwent emergent clipping surgery for subarachnoid hemorrhage under general anesthesia. Her laboratory data showed thrombocytopenia (4.0 x 10(4) microl(-1)). She had taken prednisolone (3 mg x day(-1)) and methotrexate (MTX) (10 mg x week(-1)) for rheumatoid arthritis for the last 10 years. Anesthesia was induced with remifentanil as well as propofol, maintained with remifentanil and sevoflurane in oxygen. The operation was performed uneventfully without platelet transfusion. Since the cause of thrombocytopenia was suspected to be MTX, we started rescue therapy by calcium folinate postoperatively. Platelet count was normalized two days later (11.6 x 10(4) microl(-1)). One month after the operation, she was discharged uneventfully.
21223955 Suitability of chemiluminescent enzyme immunoassay for the measurement of blood tacrolimus 2011 Apr OBJECTIVES: The aim of this study was to evaluate the suitability of chemiluminescent enzyme immunoassay (CLIA) for the monitoring of whole-blood tacrolimus concentrations in rheumatoid arthritis (RA) patients. DESIGN AND METHODS: Sixty-three RA patients and 47 renal transplant (RT) patients treated with tacrolimus were enrolled. Tacrolimus concentrations in spiked blood and patient blood were measured by CLIA and HPLC-MS/MS. The cross-reactivity in CLIA was evaluated using 13-O-demethylated or 31-O-demethylated tacrolimus. RESULTS: Tacrolimus concentrations measured by CLIA correlated with those measured by HPLC-MS/MS. Bland-Altman analysis revealed the 95% confidence intervals between CLIA and HPLC-MS/MS in RA and RT patients were -20.7 to 109.9% and -5.0 to 74.1%, respectively. While 31-O-demethylated tacrolimus cross-reaction amounted to an equivalent of 120% tacrolimus in CLIA, 13-O-demethylated tacrolimus did not cross-react. CONCLUSION: CLIA values should be carefully interpreted in RA patients, especially those receiving a low dose of tacrolimus.
22284901 Factors associated with the initiation of disease-modifying antirheumatic drugs in newly d 2012 Feb OBJECTIVES: The objectives of this study were to quantify the proportion of US patients with newly diagnosed rheumatoid arthritis (RA) in whom disease-modifying antirheumatic drug (DMARD) therapy was initiated within 12 months following diagnosis, to determine mean time to initiation, to compare the characteristics of initiators versus noninitiators, and to identify factors associated with noninitiation. METHODS: A retrospective study was conducted using claims from the databases of commercial managed care and Medicare supplemental managed care to identify patients with claims containing codes for RA dated January 1, 2004, through September 30, 2008. The percentage of patients with RA and a prescription for a DMARD within 12 months after the index date (initiators) was evaluated. The characteristics of DMARD initiators and noninitiators during the preindex period were compared, including demographic and clinical characteristics, health care resource utilization, and cost variables. The probability of DMARD initiation was determined using survival analysis. Multivariate analysis was performed to estimate mean time from diagnosis to DMARD initiation based on demographic and clinical variables. RESULTS: Of 26,911 patients with newly diagnosed RA identified in the database searches, 63% had been prescribed a DMARD within 12 months after diagnosis. DMARD initiators were significantly more likely to have had a rheumatologist visit and rheumatoid factor testing and were more likely to have received a corticosteroid and/or an NSAID (all, P < 0.001). DMARD initiators had significantly lower total costs ($10,534 vs $12,725, respectively) and pharmacy drug costs ($2438 vs $2822) over the preindex period compared with noninitiators (both, P < 0.001). Independent factors associated with a greater likelihood of DMARD initiation included a rheumatologist visit, rheumatoid factor testing, NSAID use, and corticosteroid use. Age ≥85 years and the presence of comorbidities were associated with a significantly lower likelihood of DMARD initiation. CONCLUSIONS: Among managed care enrollees in the present analysis, 37% of patients newly diagnosed with RA were not being treated with DMARDs in the first 12 months after diagnosis. Time to DMARD initiation plateaued after 90 days, suggesting that if a patient was not prescribed a DMARD soon after RA diagnosis, he or she was not likely to receive one.
23287598 Podoplanin is an inflammatory protein upregulated in Th17 cells in SKG arthritic joints. 2013 Jun Interleukin 17-producing helper T (Th17) cells play pathogenic roles in chronic inflammatory and autoimmune diseases, including arthritis, colitis and multiple sclerosis. Th17 cells selectively express the transcription factor RORγt, as well as the cytokine receptors IL-23R and CCR6. Identification of novel Th17 cell-specific molecules may have potential value as diagnostic markers in the above-mentioned inflammatory diseases. To that aim, we carried out a comparative microarray analysis on in vitro differentiated Th1, Th2, Treg and Th17 cells from naïve CD4(+) cells of BALB/c mice. Among a total of one hundred and twenty Th17 cell-specific molecules, twenty-nine were novel cell-surface molecules. Then we revealed that thirteen of them were up-regulated in vivo in inflamed tissues from experimental autoimmune diseases, including spontaneous SKG arthritis, inflammatory bowel disease (IBD) and experimental autoimmune encephalomyelitis (EAE). Next, we analyzed the expression of four membranous molecules, and revealed that podoplanin was expressed highly in the in vitro differentiated Th17 cells. Moreover, at the inflamed synovium of the arthritic SKG mice, most of the accumulating Th17 cells were podoplanin-positive. These results indicate that podoplanin would be a useful Th17 cell marker for diagnosing pathological conditions of autoimmune diseases, including rheumatoid arthritis.
21968316 A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor 2011 Dec Interleukin (IL)-6 is a pleiotropic proinflammatory cytokine involved in the pathogenesis of both atherosclerosis and rheumatoid arthritis. The role of the IL-6/IL-6 receptor pathway in the documented acceleration of atherosclerosis in rheumatoid arthritis has not been examined. In a non-randomized prospective pilot study we asked whether endothelial dysfunction, defined as impaired flow mediated dilatation (FMD), and aortic stiffness, assessed by pulse wave velocity (PWV) improve after 3 and 6 monthly therapeutic infusions of the anti-IL-6 receptor antibody tocilizumab for active rheumatoid arthritis. We found that FMD increased from 3.3 ± 0.8 to 4.4 ± 1.2 to 5.2 ± 1.9% (p = 0.003), whereas PWV decreased from 8.2 ± 1.2 to 7.7 ± 1.3 to 7.0 ± 1.0m/s (p < 0.001). Whether these beneficial arterial changes are direct effects of the IL-6/IL-6 receptor pathway inhibition, maintained over time and translate into better clinical outcome warrants further studies.
22424813 Lipid testing in patients with rheumatoid arthritis and key cardiovascular-related comorbi 2012 Aug OBJECTIVE: For patients with rheumatoid arthritis (RA) and comorbid cardiovascular disease (CVD), diabetes, or hyperlipidemia, annual lipid testing is recommended to reduce morbidity and mortality from comorbidities. Given trends encouraging complex patients to receive care in "medical homes," we examined associations between regularly seeing a primary care provider (PCP) and lipid testing in RA patients with cardiovascular-related comorbidities. METHODS: We performed a retrospective cohort study examining a 5% random USA Medicare sample (2004-06) of beneficiaries over 65 years old with RA and concomitant CVD, diabetes, or hyperlipidemia (n = 16,893). We examined the relationship between receiving lipid testing in 2006 and having at least 1 PCP visit per year in 2004, 2005, and 2006 using multivariate regression. RESULTS: Ninety percent of patients had prevalent CVD; 46% had diabetes, and 64% had hyperlipidemia. However, annual lipid testing was only performed in 63% of these RA patients. Thirty percent of patients saw a PCP less than once per year, despite frequent visits (mean >9) with other providers. Patients without at least 1 annual PCP visit were 16% less likely to have lipid testing. Increased age, complexity scores, hospitalization, and large town residence predicted decreased lipid testing. CONCLUSIONS: Despite comorbid CVD, diabetes, or hyperlipidemia, 30% of Medicare RA patients saw a PCP less than once per year, and 1 in 3 lacked annual lipid testing. Findings support advocating primary care visits at least once per year. Remaining gaps in lipid testing suggest the need for additional strategies to improve lipid testing in at-risk RA patients.
21538313 Inflammation-independent defective early B cell tolerance checkpoints in rheumatoid arthri 2011 May OBJECTIVE: Rheumatoid arthritis (RA) patients who have never received treatment for RA have been found to have defective early B cell tolerance checkpoints, resulting in impaired removal of developing autoreactive B cells. However, it is unclear whether these defects in B cell tolerance checkpoints are a primary aspect of the disease or are the result of ongoing inflammatory processes in these patients. The aim of this study was to assess the impact of standard immunosuppressive treatments, methotrexate and anti-tumor necrosis factor α (anti-TNFα) agents, on early B cell tolerance checkpoints in RA patients. METHODS: Blood samples were obtained from RA patients before and after treatment with methotrexate and/or anti-TNFα agents. B cells were tested pre- and posttherapy for reactivity of recombinant antibodies cloned from single B cells, which allowed us to determine the evolution of the frequency of autoreactive clones in the mature naive B cell compartment in RA patients before and after treatment. B cells from healthy donors were used as controls. RESULTS: Posttreatment frequencies of autoreactive mature naive B cells were elevated in the blood of RA patients. Nevertheless, the frequencies after treatment remained similar to those observed in the same patients before treatment. CONCLUSION: Despite the achievement of clinical improvement in RA patients following treatment with methotrexate and/or anti-TNFα agents, these therapies did not correct the accumulation of peripheral autoreactive mature naive B cells in these patients, suggesting that inflammation is not responsible for the defective early B cell tolerance checkpoints in RA.
22770409 Sternal insufficiency fractures of post-menopausal women: retrospective analysis of 17 cas 2012 Jun OBJECTIVE: To retrospectively investigate the clinical characteristics of sternal insufficiency fractures (SIFs) of post-menopausal women. METHODS: Findings on the clinical presentation, associated diseases, and imaging of SIFs in 17 postmenopausal women admitted to our hospital between February 1999 and January 2009 were reported. RESULTS: Twelve patients complained of severe pain in their anterior chest. Other symptoms included cough (5 cases), dyspnoea (3 cases), breathlessness (3 cases), and wheeze (2 cases). Four patients had no discomfort. The sternums of 11 cases were tender to palpation. Seventeen patients had osteoporosis. Other associated diseases were chronic obstructive pulmonary disease (7 cases), rheumatoid arthritis (3 cases), systemic lupus erythematosus (1 case), asthma (1 case), and thoracic vertebral fracture (13 cases). Nine patients had received glucocorticoid treatment. The fractures were located in the body of the sternum in 15 patients, in the manubrium in 1 patient, and in the manubriosternal junction in 1 patient. Displaced fracture was present in 13 cases. Lateral radiography of the sternum showed a fracture line in 14 patients. In the remaining 3 cases, other imaging examinations such as bone scan, computed tomography or magnetic resonance imaging demonstrated the presence of a fracture. CONCLUSIONS: Osteoporosis, glucocorticoid therapy, chronic obstructive pulmonary disease, and rheumatoid arthritis might be risk factors for SIFs. SIFs should be considered in the differential diagnosis of chest pain.
22691241 Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and ins 2012 Jun 12 INTRODUCTION: Prevalence of insulin resistance and the metabolic syndrome has been reported to be high in rheumatoid arthritis (RA) patients. Tumor necrosis factor (TNF), a pro-inflammatory cytokine with a major pathogenetic role in RA, may promote insulin resistance by inducing Ser312 phosphorylation (p-Ser312) of insulin receptor substrate (IRS)-1 and downregulating phosphorylated (p-)AKT. We examined whether anti-TNF therapy improves insulin resistance in RA patients and assessed changes in the insulin signaling cascade. METHODS: Prospective study of RA patients receiving anti-TNF agents (infliximab, n = 49, adalimumab, n = 11, or etanercept, n = 1) due to high disease activity score in 28 joints (DAS28 > 5.1). A complete biochemical profile was obtained at weeks 0 and 12 of treatment. Insulin resistance, insulin sensitivity and pancreatic beta cell function were measured by the Homeostasis Model Assessment (HOMA-IR), the Quantitative Insulin Sensitivity Check Index (QUICKI) and the HOMA-B respectively. Protein extracts from peripheral blood mononuclear cells were assayed by western blot for p-Ser312 IRS-1 and p-AKT. RA patients treated with abatacept (CTLA4.Ig) were used as a control group for insulin signaling studies. RESULTS: At study entry, RA patients with high insulin resistance (HOMA-IR above median) had significantly higher mean DAS28 (P = 0.011), serum triglycerides (P = 0.015), and systolic blood pressure levels (P = 0.024) than patients with low insulin resistance. After 12 weeks of anti-TNF therapy, patients with high insulin resistance demonstrated significant reduction in HOMA-IR (P < 0.001), HOMA-B (P = 0.001), serum triglycerides (P = 0.039), and increase in QUICKI (P < 0.001) and serum HDL-C (P = 0.022). Western blot analysis in seven active RA patients with high insulin resistance showed reduction in p-Ser312 IRS-1 (P = 0.043) and increase in p-AKT (P = 0.001) over the study period. In contrast, the effect of CTLA4.Ig on p-Ser312 IRS-1 and p-AKT levels was variable. CONCLUSIONS: Anti-TNF therapy improved insulin sensitivity and reversed defects in the insulin signaling cascade in RA patients with active disease and high insulin resistance. The impact of these biochemical changes in modifying cardiovascular disease burden in active RA patients remains to be seen.
23221584 Evolution of treatment for rheumatoid arthritis. 2012 Dec Treatment for RA has changed profoundly over the past 25 years, evolving from a strategy of providing symptomatic relief, to implementation of therapeutic regimens that impact disease activity and ultimately have been shown to slow or arrest structural joint damage. Drug therapy for RA has evolved from salicylates, to NSAIDs, CSs, DMARDs, MTX, and finally to biologic response modifiers. MTX has become the initial drug of choice in most patients with RA, and some do well on MTX monotherapy without the addition of other agents. Combination regimens including MTX and other conventional DMARDs may be an effective early approach to treatment of RA. The biologic response modifiers (biologics) became available in the late 1990s, based on our understanding of the molecular mediators of synovial inflammation in RA. The first biologics inhibited TNF-α, a cytokine active in host defences against some infections and malignancies, but which also promotes inflammation and bone erosion. Inhibitors of TNF-α are mostly given with MTX, although some can be given as monotherapy. Studies consistently show that combination MTX + TNF-α inhibitor therapy leads to better outcomes than with either agent alone. Tight control strategies, employing objective measures, also lead to improved outcomes. When patients fail treatment with one or more TNF-α inhibitor + MTX, a number of other possible alternatives may be tried, including treatment with biologics having other mechanisms, such as antibodies to certain ILs, other cytokines and inflammatory mediators. Current therapy for RA is such that progression from symptom onset to significant disability is now no longer inevitable, and RA patients can anticipate comfortable and productive lives on medical therapy.
21906424 Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the I 2011 May Given the availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), various national scientific societies have developed specific recommendations in order to assist rheumatologists in prescribing these drugs. The Italian Society for Rheumatology (Società Italiana di Reumatologia, SIR) decided to update its recommendations, and, to this end, a systematic literature review was performed and the evidence derived from it was discussed and summarized as expert opinions. Levels of evidence and strength of recommendations were reported. The recommendations reported refer to the safety of biologic agents and are intended to help prescribing rheumatologists to optimise the use of biologic agents in patients with RA seen in everyday practice; they are not to be considered as a regulatory rule.
23239179 Measuring methotrexate polyglutamates in red blood cells: a new LC-MS/MS-based method. 2013 Feb The folate antagonist methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis. The therapeutic effects of MTX are attributed to the intracellular levels of MTX, present in the cell as polyglutamates (MTXPGn). We developed a new liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)-based assay to separately quantitate MTXPGn in red blood cells using stable-isotope-labelled internal standards. Samples were analyzed by LC-ESI-MS/MS using a Waters Acquity UPLC BEH C18 column with a 5-100% organic gradient of 10 mM ammonium bicarbonate (pH 10) and methanol. The analysis consisted of simple sample preparation and a 6-min run time. Detection was done using a Waters Acquity UPLC coupled to a Waters Quattro Premier XE with electrospray ionization operating in the positive ionization mode. Assay validation was performed following recent Food and Drug Administration guidelines. The method was linear from 1-1,000 nM for all MTXPGn (R(2) > 0.99). The coefficient of variation ranged from 1-4% for intraday precision and 6-15% for interday precision. Samples were stable for at least 1 month at -80 °C. Recovery ranged from 98-100%, and the relative matrix-effect varied from 95-99%. The lower limit of quantitation was 1 nM for each MTXPGn. Fifty patient samples from the tREACH study were analyzed. The MTXPGn concentration and distribution of these samples were comparable with values reported in literature. The developed LC-ESI-MS/MS method for the quantitative measurement of MTXPGn in red blood cells is both sensitive and precise within the clinically relevant range. The method can be easily applied in clinical laboratories due to the combination of simple pre-treatment with robust LC-ESI-MS/MS.
23359966 [External application of compound Tripterygium wilfordii decreased the activity of rheumat 2012 Nov OBJECTIVE: To explore the therapeutic efficacy of external application of Compound Tripterygium wilfordii (CTW) for treating rheumatoid arthritis (RA) on the basis of treatment by integrative medicine. METHODS: Totally 67 active RA patients of damp-heat stagnation syndrome were randomly assigned to the external application group (35 cases) and the placebo group (32 cases). The reaction standard by American College of Rheumatology and Disease Activity Score (DAS) were taken as the indices for therapeutic assessment. A randomized controlled, single blind clinical trial was performed for 4 weeks, with a 3-month follow-up. The statistical analyses were performed using intention to treat analysis set (ITT). RESULTS: After treatment the rate of reaching ACR20 was 34.3% and 12.5% in the external application group and the placebo group respectively. The mean for the average drop of DAS28 ratings was 1.07 in the external application group and 0.40 in the placebo group, showing statistical difference (P < 0.05, P < 0.01). As for the safety, there was no effect on the menstruation in the external application group. Only mild skin allergy occurred in 2 cases of the external application group, but they were alleviated after drug withdrawal. CONCLUSIONS: External application of CTW could control the condition of RA and reduce the disease activity of RA. It had better safety.
21652584 Evidence for the efficacy of complementary and alternative medicines in the management of 2011 Sep OBJECTIVE: To critically evaluate the evidence regarding complementary and alternative medicine (CAM) taken orally or applied topically (excluding fish oil) in the treatment of RA. METHODS: Randomized controlled trials (RCTs) of RA using CAMs, in comparison with other treatments or placebo, published in English up to August 2010, were eligible for inclusion. They were identified using systematic searches of bibliographic databases and manual searching of reference lists. Information was extracted on outcomes and statistical significance, in comparison with alternative treatments, and reported side effects. The methodological quality of the primary studies was determined using the Jadad scoring system. RESULTS: Reported RCTs were available for 18 CAMs in the management of RA. There was no consistent evidence available for any of the reviewed substances to suggest that they were efficacious as complementary medicines to standard treatment. Nevertheless, the studies conducted on borage seed oil (n = 2) and thunder god vine (n = 3) have been positive and may warrant further investigation. Not all CAM compounds studied were free of major adverse effects. CONCLUSION: The major limitation in reviewing the evidence for CAMs is the paucity of RCTs in the area. The available evidence does not support their current use in the management of RA.
21292737 Fertility in women with chronic inflammatory arthritides. 2011 Jun OBJECTIVE: To compare fertility rates in women with RA, other chronic arthritides (OCAs) and JIA with reference women from the general population. METHODS: Each woman from a Norwegian patient registry was matched by year of birth with 100 reference women randomly selected from the National Population Registry. Data linkage of patients and references with the Medical Birth Registry of Norway (MBRN) identified all offspring in patients and references until October 2007, and indirectly also nulliparous (childless) women. Groups were compared with Mann-Whitney U-test for continuous variables and chi-squared tests for categorical variables. Poisson regression analysis was applied to calculate relative fertility rates in the diagnostic groups vs references. RESULTS: Among 631 patients 849 children were registered in MBRN. Of these, 289 children (34.0%) were born after time of diagnosis vs 44.3% in references. Altogether, 206 of 631 patients (32.6%) were nulliparous vs 26.4% in references (P < 0.001). Among RA patients, 28.4% (96 of 338) were nulliparous vs 24.5% in references (P = 0.09), 30.7% (67 of 218) in OCA patients vs 24.5% in references (P = 0.03) and 57.3% (43 of 75) in JIA patients vs 40.9% in references (P = 0.004). Adjusted relative fertility rates in RA, OCA and JIA after diagnosis were 0.88, 0.84 and 0.84, respectively, compared with references. CONCLUSION: A higher proportion of women with chronic inflammatory arthritides were nulliparous compared with references, and relative fertility rates were reduced in all patient groups.
22392503 Role of the CCL21 and CCR7 pathways in rheumatoid arthritis angiogenesis. 2012 Aug OBJECTIVE: To determine the role of CCL21 and its receptor CCR7 in the pathogenesis of rheumatoid arthritis (RA). METHODS: Histologic studies were performed to compare the expression of CCR7 and CCL21 in RA synovial tissue. Next, the role of CCL21 and/or CCR7 in angiogenesis was examined using in vitro chemotaxis, tube formation, and in vivo Matrigel plug assays. Finally, the mechanism by which CCL21 mediates angiogenesis was determined by Western blot analysis and endothelial cell chemotaxis and tube formation assays. RESULTS: CCL21, but not CCL19, at concentrations present in the RA joint, induced human microvascular endothelial cell (HMVEC) migration that was mediated through CCR7 ligation. Suppression of the phosphatidylinositol 3-kinase pathway markedly reduced CCL21-induced HMVEC chemotaxis and tube formation; however, suppression of the ERK and JNK pathways had no effect on these processes. Neutralization of either CCL21 in RA synovial fluid or CCR7 in HMVECs significantly reduced the induction of HMVEC migration and/or tube formation by RA synovial fluid. We further demonstrated that CCL21 is angiogenic, by showing its ability to promote blood vessel growth in Matrigel plugs in vivo at concentrations that are present in RA joints. CONCLUSION: Angiogenesis is dependent on endothelial cell activation, migration, and proliferation, and inhibition of angiogenesis may provide a novel therapeutic approach in RA. This study identified a novel function of CCL21 as a mediator of RA angiogenesis, supporting CCL21/CCR7 as a therapeutic target in RA.
20024555 Serum chemokines in patients with rheumatoid arthritis treated with etanercept. 2011 Apr Chemokines promote leucocyte traffic into the synovium, leading to the initiation and progression of the rheumatoid arthritis (RA). The aim of the study was to determine the effects of etanercept, a soluble tumour necrosis factor receptor (sTNFr), on the serum chemokines levels in patients with active RA. Patients were treated with 50 mg of subcutaneous injection of etanercept per week and methotrexate (10-25 mg/week). Serum levels of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at months 0, 3, 6, 9 and 12, prior to injection. 3-month treatment with etanercept diminished serum concentrations of IL-8, RANTES and MCP-1 (P < 0.05, P < 0.01 and P < 0.001, respectively). Subsequent etanercept administrations prolonged decrease in serum chemokines levels and in the case of IL-8 even intensified the reduction of its concentration in serum. These changes were accompanied by significant decrease of disease activity score (DAS28) (in all cases P < 0.001). Prior to the first etanercept administration, serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) and DAS28. Following next drug injection such associations were less or not significant. Therapy with etanercept and MTX not only caused a clinical improvement but also diminished serum chemokines levels in RA patients. Further treatment with etanercept sustained chemokines suppression.