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ID PMID Title PublicationDate abstract
27051232 Bone Scintigraphy in the Diagnosis of Rheumatoid Arthritis: Is There Additional Value of B 2016 Apr We aimed to investigate the value of bone scintigraphy with additional blood pool phase (BSBP), compared with conventional bone scintigraphy (CBS), in the assessment of rheumatoid arthritis (RA). A total of 242 patients (43 males, 199 females; 14-78 years) with arthralgia, and underwent BSBP were retrospectively analyzed. On the first physical examination, active arthritis was found in 128 of the 242 patients. Clinical diagnosis was made by a rheumatologist on the basis of the 1987 American College of Rheumatology (ACR) criteria, which are considered to be the gold standard. The diagnostic performances and prognostic value of BSBP and CBS were analyzed in the total patients with arthralgia and in the patients with arthritis. The sensitivity of BSBP (84.2%, 80/95) were significantly higher than that of CBS (74.8%, 72/95) in the patients with arthralgia (P = 0.039). When BSBP was interpreted with the results of elevated/positive anti-CCP antibody, its accuracy over CBS also became significantly higher (86.0%, 208/242 vs. 83.1%, 201/242 respectively, P = 0.021). The diagnostic odds ratio of BSBP positivity was higher than CBS positivity in the patients with arthralgia (26.0, 12.9-52.4 vs. 21.1, 10.8-41.3) and with arthritis (12.0, 4.9-29.4 vs. 10.0, 4.2-23.4). Both BSBP and CBS appear to provide acceptable accuracy and comparable diagnostic performance for diagnosis of RA. However, in the patients with arthralgia, BSBP was found to be more sensitive than CBS and more accurate when interpreted with the result of anti-CCP antibody. This could help physicians diagnose RA in daily clinical practice.
26656538 Glabretal-type triterpenoid from the root bark of Dictamnus dasycarpus ameliorates collage 2016 Feb 3 ETHNOPHARMACOLOGICAL RELEVANCE: The root bark of Dictamnus dasycarpus Turcz. (Rutaceae) has been used as a traditional herbal medicine to treat various inflammatory diseases in East Asia. We have showed previously that a glabretal type triterpenoid (dictabretol A) from D. dasycarpus root bark has immunosuppressive activity. AIM OF THE STUDY: This study was conducted to define the molecular mechanism of how dictabretol A inhibits lymphocyte proliferation and to evaluate the therapeutic efficacy of dictabretol A in an animal model of rheumatoid arthritis. MATERIALS AND METHODS: Various murine immune cells (T cells, B cells, and macrophages) and splenocytes were used to study the anti-proliferative effect of dictabretol A in vitro. A collagen-induced arthritis model was also used to examine the therapeutic effect of dictabretol A in vivo. RESULTS: Dictabretol A specifically inhibited lymphocyte proliferation by blocking the cell cycle transition from the G1 to the S phase. This effect was achieved by blocking Erk1/2, nuclear factor kappa B, and the C-myc axis of cell cycle progression. Further dictabretol A treatment alleviated the severity of collagen-induced arthritis. CONCLUSION: Our results reveal the molecular mechanism for the anti-lymphoproliferative effect of dictabretol A and show the therapeutic efficacy of dictabretol A for rheumatoid arthritis.
28026971 Assessment of Corneal and Tear Film Parameters in Rheumatoid Arthritis Patients Using Ante 2018 PURPOSE: To study the corneal changes in rheumatoid arthritis (RA) patients in vivo, using spectral domain anterior segment optical coherence tomography (AS-OCT). METHODS: A case-control study was done on 43 RA patients and 40 controls. The disease activity score (DAS28-ESR) was calculated and all participants had lower tear meniscus, corneal thickness, and epithelial thickness evaluation using AS-OCT. RESULTS: The lower tear meniscus height (LTMH) and the lower tear meniscus area (LTMA) were significantly lower in the RA patients than in controls (p < 0.001). RA patients also had a significantly thinner central corneal thickness (p = 0.02) and their epithelium was found to be thinner in the superotemporal peripheral sector. CONCLUSIONS: The LTMH and LTMA are significantly reduced in RA patients, despite the absence of clinical diagnosis of dry eye. RA patients have thinner corneal thickness and epithelial thickness than controls, which did not correlate with either disease duration or activity.
25658465 Surgical outcomes of long spinal fusions for scoliosis in adult patients with rheumatoid a 2015 Apr OBJECT: In this study, the authors compared outcomes and complications in patients with and without rheumatoid arthritis (RA) who underwent surgery for spinal deformity. METHODS: The authors searched the Johns Hopkins University database for patients with RA (Group RA) and without RA (Group NoRA) who underwent long spinal fusion for scoliosis by 3 surgeons at 1 institution from 2000 through 2012. Groups RA and NoRA each had 14 patients who were well matched with regard to sex (13 women/1 man and 12 women/2 men, respectively), age (mean 66.3 years [range 40.5-81.9 years] and 67.6 years [range 51-81 years]), follow-up duration (mean 35.4 months [range 1-87 months] and 44 months [range 24-51 months]), and number of primary (8 and 8) and revision (6 and 6) surgeries. Surgical outcomes, invasiveness scores, and complications were compared between the groups using the nonpaired Student t-test (p < 0.05). RESULTS: For Groups RA and NoRA, there were no significant differences in the average number of levels fused (10.6 [range 9-17] vs 10.3 [range 7-17], respectively; p = 0.4), the average estimated blood loss (2892 ml [range 1300-5000 ml] vs 3100 ml [range 1700-5200 ml]; p = 0.73), or the average invasiveness score (35.5 [range 21-51] vs 34.5 [range 23-58]; p = 0.8). However, in Group RA, the number of major complications was significantly higher (23 vs 11; p < 0.001), the number of secondary procedures was significantly higher (14 vs 6; p < 0.001), and the number of minor complications was significantly lower (4 vs 12; p < 0.001) than those in Group NoRA. CONCLUSIONS: Long spinal fusion in patients with RA is associated with higher rates of major complications and secondary procedures than in patients without RA.
26821282 Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect it 2016 Mar G protein signaling modulator 3 (GPSM3) is a regulator of G protein-coupled receptor signaling, with expression restricted to leukocytes and lymphoid organs. Previous genome-wide association studies have highlighted single-nucleotide polymorphisms (SNPs; rs204989 and rs204991) in a region upstream of the GPSM3 transcription start site as being inversely correlated to the prevalence of rheumatoid arthritis (RA)-this association is supported by the protection afforded to Gpsm3-deficient mice in models of inflammatory arthritis. Here, we assessed the functional consequences of these polymorphisms. We collected biospecimens from 50 volunteers with RA diagnoses, 50 RA-free volunteers matched to the aforementioned group and 100 unmatched healthy young volunteers. We genotyped these individuals for GPSM3 (rs204989, rs204991), CCL21 (rs2812378) and HLA gene region (rs6457620) polymorphisms, and found no significant differences in minor allele frequencies between the RA and disease-free cohorts. However, we identified that individuals homozygous for SNPs rs204989 and rs204991 had decreased GPSM3 transcript abundance relative to individuals homozygous for the major allele. In vitro promoter activity studies suggest that SNP rs204989 is the primary cause of this decrease in transcript levels. Knockdown of GPSM3 in THP-1 cells, a human monocytic cell line, was found to disrupt ex vivo migration to the chemokine MCP-1.
26473946 Rheumatoid Arthritis and Mortality Among Women During 36 Years of Prospective Follow-Up: R 2016 Jun OBJECTIVE: To evaluate rheumatoid arthritis (RA) and mortality risk among women followed prospectively in the Nurses' Health Study (NHS). METHODS: We analyzed 119,209 women in the NHS who reported no connective tissue disease at enrollment in 1976. Comorbidity and lifestyle data were collected through biennial questionnaires. Incident RA cases were validated by medical records review. Cause of death was determined by death certificate and medical records review. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause, cardiovascular disease (CVD), cancer, and respiratory disease mortality for women with RA compared to those without RA. RESULTS: We validated 964 incident RA cases and identified 28,808 deaths during 36 years of prospective follow-up. Of 307 deaths among women with RA, 80 (26%) were from cancer, 70 (23%) were from CVD, and 44 (14%) were from respiratory causes. Women with RA had increased total mortality (HR 1.40, 95% CI 1.25-1.57) compared to those without RA, independent of mortality risk factors, including smoking. RA was associated with significantly increased respiratory disease mortality (HR 2.06, 95% CI 1.51-2.80) and cardiovascular disease mortality (HR 1.45, 95% CI 1.14-1.83), but not cancer mortality (HR 0.93, 95% CI 0.74-1.15). For women with seropositive RA, respiratory disease mortality was nearly 3-fold higher than among non-RA women (HR 2.67, 95% CI 1.89-3.77). CONCLUSION: Women with RA had significantly increased mortality compared to those without RA. Respiratory disease and cardiovascular disease mortality were both significantly elevated for women with RA. The nearly 3-fold increased relative risk of respiratory disease mortality was observed only for those with seropositive RA.
28012023 Oral to subcutaneous methotrexate dose-conversion strategy in the treatment of rheumatoid 2017 Feb Both the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) guidelines recommend the use of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA) when there is no contraindication. While MTX is the foundation of RA therapy (Singh et al. in Arthritis Care Res 64:625-639,2012), absorption saturation compromises its oral bioavailability (BA). Differences in the relative BA of oral versus subcutaneous (SC) MTX demonstrate the need for guidance on successful dose-conversion strategies. This study was designed to compare MTX PK profiles as a result of MTX administration via three different treatment administrations: oral, SC MTX administered via an auto-injector (MTXAI) into the abdomen (MTXAI(ab)) and into the thigh (MTXAI(th)). In this paper, we establish a dose-conversion method based on the BA of MTX from oral and SC administration. SC administration provided higher exposure of MTX than the same dose given orally. Unlike the exposure limitations of oral MTX, dose-proportional exposure was seen with SC MTX.
26268325 Cytokine detection and simultaneous assessment of rheumatoid factor interference in human 2015 Aug 13 BACKGROUND: Fluorescence-enhancing microarray on plasmonic gold film is an attractive alternative to traditional enzyme-linked immunosorbent assay (ELISA) for cytokine detection because of the increased sensitivity. The assay chemistry is similar to an ELISA sandwich assay, but owing to the gold substrate, cytokine measurements are 10 to 100 times more sensitive and can be multiplexed. Plasmonic protein microarrays are, as other immunoassays, affected by the presence of heterophilic antibodies and rheumatoid factor may lead to analytical errors with serious implications for patient care. Here, we present a plasmonic gold substrate protein microarray for high-sensitivity detection of cytokines with simultaneous assessment of rheumatoid factor interference on a single chip. RESULTS: Paired serum and synovial fluid samples from patients with rheumatoid arthritis (n = 18), osteoarthritis (n = 9) or healthy controls (n = 10) were arrayed on near-infrared fluorescence enhancing plasmonic gold chips spotted with cytokine-specific capture antibody and isotype control antibody. Possible rheumatoid factor interference was visualised by a non-specific signal from the isotype control antibody, and pre-treatment of samples with heat-aggregated animal IgG eliminated this background contamination. The platform was optimised using the cytokine IL-20. The protein microarray platform allowed for the detection of human IL-20 at levels <1 pg/ml with reliable IL-20 quantification over a 5-log dynamic range. Samples for which rheumatoid factor caused artefacts were identified and a method for eliminating rheumatoid factor interference was developed and validated. IL-20 protein levels were significantly higher in synovial fluid samples from patients with rheumatoid arthritis compared to osteoarthritis (p < 0.001), while serum levels of IL-20 did not differ between patients with rheumatoid arthritis, osteoarthritis or healthy controls. CONCLUSION: Using novel plasmonic gold chips, we developed a highly sensitive and accurate assay platform to detect lowly expressed cytokines in biological fluids, allowing for the elimination of rheumatoid factor interference in as little as 5 μl sample volume. The detection limit was below 1 pg/ml for IL-20 and linearity was achieved over a 5-log dynamic range. This technology is highly advantageous for cytokines where sensitivity or sample volume is critical or where assessment of rheumatoid factor interference needs addressed and eliminated.
25854159 Polymorphisms of MMP-1 and MMP-3 and susceptibility to rheumatoid arthritis. A meta-analys 2015 Apr OBJECTIVE: To determine the correlation between rheumatoid arthritis (RA) and polymorphisms of the matrix metalloproteinase (MMP) genes MMP-1 and MMP-3. BACKGROUND: The 1607 1G/2G and 1171 5A/6A polymorphisms of MMP genes MMP-1 and MMP-3 have been discovered to be functional, and may be conducive to RA. In order to determine whether MMP-1 and MMP-3 gene polymorphisms correlate with RA development, we performed a meta-analysis to further validate the function of these polymorphisms in RA. METHODS: We searched PubMed, ISI Web of Knowledge, MEDLINE, Embase, Google Scholar Chinese Biomedical Literature Database, and Wanfang Data to identify all published case-control studies on the MMP-1-1607 1G/2G and MMP-3-1171 5A/6A polymorphisms and RA risk. Odds ratios (OR) and 95 % confidence intervals (CI) were used to estimate the association between these polymorphisms and RA risk. RESULTS: After being assessed, five articles fulfilled the inclusion criteria. To assess associations, the pooled OR with 95 % CIs was calculated. Neither the MMP-1-1607 1G/2G nor the MMP-3-1171 5A/6A polymorphism was statistically associated with RA in any of the five models, nor in the subgroup analysis models of MMP-3-1171 5A/6A in Caucasian and Asian patients. CONCLUSION: Our study suggests that MMP-1 and MMP-3 polymorphisms have no significant association with the risk of RA.
26513681 The effect of rheumatoid arthritis and functional loading on the structure of the mandibul 2016 Jan OBJECTIVE: The objective of the present study was to investigate the effect of rheumatoid arthritis and functional loading through diet modification on the biochemical properties of the mandibular condyle in a transgenic mouse model and compare with healthy littermates. DESIGN: Twenty three, 4-week old hybrid male mice were used. Eleven were of transgenic line hTNF 197 (Tg 197 - with rheumatoid arthritis - RA) and 12 healthy littermates, both from mixed background CBAxC57BL/6. Four groups of mice were formed. Group 1 [n =5, RA-hard] included transgenic mice and received ordinary (hard) diet; group 2 [n=6, RA-soft] included transgenic line and received soft diet; group 3 [n=6, control-hard] were healthy littermates receiving ordinary (hard) diet and group 4 [n=6, control-soft] were healthy littermates with soft diet. Experimental period was 28 days. Following sacrifice, the mandibular condyles were subjected to micro-attenuated reflection Fourier transform infrared spectroscopy (micro-ATR FTIR) to reveal collagen/proteoglycan conformation of the condylar cartilage, while resin-embedded and metallographically polished specimens were evaluated through reflection FTIR microscopy to identify mineralization status of the corresponding condylar bone. RESULTS: The multivariable analysis revealed significantly lower a-helix to amide I percentage area ratio for the transgenic animals after adjusting for diet (β=-4.29, 95% CIs: -8.52, -0.06; p=0.04). Mineral phase indices did not differ significantly between RA and control groups regardless the type of diet. CONCLUSIONS: Internal derangement of the anatomical structure with denaturation in the collagen structural components of the mandibular condyles of the RA animals was found, while no association with functional loading through diet modification was recorded.
27214094 Dose down-titration of biological DMARDs in patients with rheumatoid arthritis over time a 2016 Sep OBJECTIVES: To describe and compare dosing optimisation in biological DMARDs (bDMARDs) and relapses after that, in a cohort of rheumatoid arthritis (RA) during clinical practice. METHODS: Observational retrospective longitudinal study of RA patients taking bDMARDs from December 1999 to November 2013. Optimisation was defined as a 15% decrease in dose either reducing single dose or separating dose interval administration, for at least 4 times the recommended period between dosages. Relapse was defined as suspension or starting again with the recommended dose after optimisation. Incidence rates (IR) per 100 patient-years were estimated using survival techniques. Cox multivariate models were conducted to compare bDMARDs expressed in hazard ratios (HR) and confidence intervals [95%CI]. RESULTS: 443 patients and 752 different courses of bDMARDs treatments were included. We observed 146 optimisations with an IR of 8.1. The HR of optimisation in: a) adalimumab, etanercept and rituximab compared to infliximab was 1.56 [1.01-2.4], 1.5 [0.9-2.4] and 0.6 [0.3-1.4], respectively; b) adalimumab, etanercept compared to rituximab were 2.3 [1.2-4.5] and 2.2 [1.2-4.3]. There were no statistically significant differences between adalimumab and etanercept. Following optimisation, 36% relapsed (78% due to disease activity). The IR related to disease activity was 6.3, and was lower for adalimumab and etanercept compared to infliximab (HR: 0.42; [0.19-0.94]; HR: 0.34; [0.13-0.89], respectively). There were no statistically significant differences between etanercept and adalimumab. No patients on rituximab relapsed. CONCLUSIONS: Optimisation was similar between adalimumab and etanercept, and was lower for infliximab and rituximab. After optimisation, rituximab did not relapse, but infliximab did with the highest hazard.
25139185 Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and 2015 May AIM: The purpose of this work was to evaluate epicardial adipose tissue (EAT), carotid intima-media thickness (CIMT), and flow-mediated dilatation (FMD) of the brachial artery in rheumatoid arthritis (RA) patients using ultrasonographic methods. Interrelationships between these three parameters in RA patients were also investigated. METHODS: EAT thickness, CIMT, and FMD were measured by ultrasonography. We measured the disease activity score (DAS28), health assessment questionnaire (HAQ) score, and C-reactive protein (CRP) levels. Spearman or Pearson correlation analysis was used to evaluate the association between clinical findings, CIMT, FMD, and EAT. RESULTS: A total of 90 RA patients [19 men, mean age 54 years (range 21-76 years)] and 59 age- and gender-matched control subjects [17 men, mean age 54 years (range 26-80 years)] were included in the study. Patients with RA had a mean 4.34 DAS28 points (range 0-40 points) and the mean duration of the disease was 77.1 months (range 1-360 months). We found that RA patients had thicker EAT (7.7 ± 1.7 mm vs 6.2 ± 1.8 mm, p < 0.001), increased CIMT [0.9 (0.5-1.2) mm vs 0.6 (0.4-0.9) mm, p < 0.001], and decreased FMD values [5.7 % (- 23.5 to 20 %) vs. 8.5 % (- 4.7 to 22.2 %), p = 0.028] when compared to control subjects. CRP levels were significantly higher in the RA group [0.81 (range 0.1-13.5) vs 0.22 (range 0.05-12), p < 0.001]. EAT thickness was negatively correlated with FMD (r = - 0.26, p < 0.001) and positively correlated with CIMT values (r = 0.52, p < 0.001). CIMT also negatively correlated with FMD (r = - 0.29, p < 0.001). CONCLUSION: EAT can be simply measured by echocardiography and correlated with FMD and CIMT. It can be used as a first-line measurement for estimating burden of atherosclerosis in RA patients.
26965417 Incidence and risk factors of fractures in patients with rheumatoid arthritis: an Asian pr 2016 Sep Rheumatoid arthritis (RA) patients have high risk for osteoporosis and fracture. We aimed to identify the incidence rate and risk factors of fractures in Asian RA patients. A total of 3557 RA patients in the KORean Observational study Network for Arthritis (KORONA) were included and observed over a mean follow-up of 18 months. A fracture was assessed as total, major, or minor fractures; major fracture was defined as a vertebral or hip fracture, and the other fractures were classified as minor fractures. The standardized incidence ratio (SIR) of fracture in RA patients was calculated compared with general population, and possible risk factors for fractures were explored using multivariable logistic regression analyses. A total of 194 patients with 215 fractures were observed, and the SIR of the total fracture in RA patients was 2.2 [95 % confidence interval (CI) 1.9-2.6]. The SIRs of major and minor fractures were 1.5 (CI 1.1-2.0) and 3.0 (CI 2.5-3.7), respectively. Advanced age [odds ratio (OR) 1.03, CI 1.02-1.05, p < 0.01] and having history of prior fracture (OR 2.17, CI 1.54-3.08, p < 0.01) were risk factors for total fractures. In addition, higher HAQ increased fracture risk (OR 2.02, CI 1.05-3.89, p = 0.04), whereas the use of bisphosphonate showed protective effect for future fractures (OR 0.34, CI 0.14-0.87, p = 0.02) in patients with osteoporosis. RA patients had a 2.2-fold increased risk of fractures as compared with general population. In Asian RA patients, advanced age and history of prior fracture were the most important risk factors for new fractures.
26743640 MS arising during Tocilizumab therapy for rheumatoid arthritis. 2016 Feb BACKGROUND: Interleukin-6 (IL6) blockage is a treatment strategy used in many inflammatory conditions. Trials in Neuromyelitis Optica Spectrum Disorder (NMOSD) are ongoing. Secondary auto-immunity affecting the central nervous system (CNS) is well described with some biologic agents, mainly tumor necrosis factor (TNF)-alpha inhibitors. These treatments can also aggravate patients with known multiple sclerosis (MS). OBJECTIVES: To describe a case of a patient who developed MS using another biologic, IL6 receptor antibody Tocilizumab. RESULTS: A 48-year-old woman developed MS while on treatment with Tocilizumab for Rheumatoid Arthritis (RA). This is the first published report of this association. It has obvious implications for NMOSD patients receiving anti-IL6 therapy. Development of new white matter lesions suggestive of MS in a patient treated with anti-IL6 therapy might represent an important complication of therapy. CONCLUSION: This case illustrates that Tocilizumab might cause secondary auto-immunity in CNS. It is important to be aware of this potential complication as anti-IL6 therapy might become an option for the treatment NMOSD.
26233511 Discordance of Global Assessments by Patient and Physician Is Higher in Female than in Mal 2015 Oct OBJECTIVE: To assess the frequency of discordance in patient's (PtGA) and physician's (PGA) global assessment, and to investigate whether higher discordance in female patients compared with male patients is associated with the physician's sex in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). METHODS: PtGA, PGA, and other patient-related variables were retrieved from the Danish DANBIO registry, used nationwide to monitor patients with RA, axSpA, and PsA. A questionnaire was sent to all physicians registering in DANBIO (n = 265) regarding individual physician characteristics including sex and age. Discordance was defined as PtGA > 20 mm higher (or lower) than PGA. First encounters between patients and physicians were analyzed using descriptive statistics and mixed model regression analysis. RESULTS: Ninety physicians (34%) returned the questionnaire and were pairwise matched with 10,282 first patient encounters (8300 patients with RA, 524 axSpA, and 1458 PsA). The frequency of discordant (PtGA > PGA) encounters (not including PGA > PtGA seen in < 2%) in RA, axSpA, and PsA was 49.0%, 48.3%, and 56.5%, respectively. Discordance was more common in female patients with high scores on functional disability, pain, and fatigue across the 3 diseases, whereas it was independent of the physician's sex. CONCLUSION: In this study on Danish patients with RA, axSpA, and PsA, the PtGA was > 20 mm higher than the PGA in about half of the encounters, and more common in female patients of both female and male physicians. This finding highlights one of the challenges in shared decision making.
28013187 Halofuginone inhibits TNF-α-induced the migration and proliferation of fibroblast-like sy 2017 Feb Fibroblast-like synoviocytes (FLSs) display an aggressive phenotype that is a critical factor in cartilage destruction in rheumatoid arthritis (RA). Increased FLS migration and proliferation are essential to the pathology of RA. Halofuginone has been found to inhibit cell migration and proliferation in cancer cells. However, whether halofuginone has a role in the treatment of RA FLSs is unclear. In this study, we found that halofuginone reduced migration, invasion, cell proliferation and MMPs expression in RA FLSs. In addition, we demonstrated that halofuginone inhibited reorganization of the actin cytoskeleton during cell migration. To gain insight into the molecular mechanisms, we evaluated the effect of halofuginone on the MAPK and AKT pathways. Our results indicated that halofuginone inhibited the activity of MAPK and AKT. Taken together, these results suggest that halofuginone may protect against joint destruction in RA by regulating synoviocyte migration, invasion and cell proliferation by inhibiting MAPK and AKT activation.
25349113 The miR-146a polymorphism and susceptibility to systemic lupus erythematosus and rheumatoi 2015 Mar OBJECTIVE: The aim of this study was to explore whether the miR-146a polymorphism (rs2910164) confers susceptibility to systemic lupus erythematous (SLE) and rheumatoid arthritis (RA). METHODS: A meta-analysis was conducted on the association of the miR-146a polymorphism with SLE and RA. RESULTS: Five studies with 2013 patients and 2555 controls were included in the meta-analysis. Meta-analysis revealed no association between SLE and the miR-146a G allele (odds ratio, OR = 1.007, 95 % confidence interval, CI = 0.910-1.114, p = 0.888). Additionally, no associations were found between the miR-146a polymorphism and SLE using recessive or dominant models, or homozygote contrast. Meta-analysis using allele contrast, recessive and dominant models, as well as homozygote contrast failed to reveal an association between the miR-146a polymorphism and RA (OR for G allele = 1.114, 95 % CI = 0.892-1.391, p = 0.342). CONCLUSION: This meta-analysis demonstrates that the miR-146a polymorphism is not associated with susceptibility to SLE and RA. However, considering the small number of studies, further studies are needed to confirm this result.
27324632 Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies w 2016 Aug To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5-3.5) and bone erosion (OR = 2.9, 95 % CI 1.1-7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9-204.4 for RA and OR = 69.4, 95 % CI 15.8-305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.
27474075 In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Imm 2016 Sep 1 IL-33 is strongly involved in several inflammatory and autoimmune disorders with both pro- and anti-inflammatory properties. However, its contribution to chronic autoimmune inflammation, such as rheumatoid arthritis, is ill defined and probably requires tight regulation. In this study, we aimed at deciphering the complex role of IL-33 in a model of rheumatoid arthritis, namely, collagen-induced arthritis (CIA). We report that repeated injections of IL-33 during induction (early) and during development (late) of CIA strongly suppressed clinical and histological signs of arthritis. In contrast, a late IL-33 injection had no effect. The cellular mechanism involved in protection was related to an enhanced type 2 immune response, including the expansion of eosinophils, Th2 cells, and type 2 innate lymphoid cells, associated with an increase in type 2 cytokine levels in the serum of IL-33-treated mice. Moreover, our work strongly highlights the interplay between IL-33 and regulatory T cells (Tregs), demonstrated by the dramatic in vivo increase in Treg frequencies after IL-33 treatment of CIA. More importantly, Tregs from IL-33-treated mice displayed enhanced capacities to suppress IFN-γ production by effector T cells, suggesting that IL-33 not only favors Treg proliferation but also enhances their immunosuppressive properties. In concordance with these observations, we found that IL-33 induced the emergence of a CD39(high) Treg population in a ST2L-dependent manner. Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development.
27193469 Anxiety and depression in rheumatoid arthritis: an epidemiologic survey and investigation 2016 Aug Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA). This study was conducted in order to evaluate the prevalence of anxiety and depression in Iranian RA patients. In the cross sectional study, 414 RA patients were enrolled prospectively during a period of 6 months from RA clinic of Rheumatology Research Center. Beck's and Cattell's inventories were applied to investigate depression and anxiety in RA patients. RA activity was measured by Disease Activity Score and patients' disability was assessed by Health Assessment Questionnaire. Levels of pain perception were stratified based on Visual Analog Scale. The prevalence of depression was 63.6 % and anxiety was in 84.1 % among RA patients. Mixed anxiety and depression was detected in 60.2 % of the study population. Functional disability was significantly associated with severity of depressive and anxiety symptoms (p < 0.001); however there was no association between disease activity and depression or anxiety (p = 0.420). There was weak correlation between disease activity score and functional disability (Spearman's rho = 0.33; p < 0.01). Severe levels of depression and anxiety were associated with higher levels of pain perception (p < 0.001). Our study stressed the impact of depressive and anxiety symptoms in functional disability and pain perception of RA patients. Our results point out the multidisciplinary management of RA.