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ID PMID Title PublicationDate abstract
25028787 Anti-C1q in chronic hepatitis C virus genotype IV infection: association with autoimmune r 2015 A growing body of evidence suggests that anti-complement-1q (anti-C1q) antibodies are elevated in a variety of autoimmune disease. Therefore, we investigated their prevalence and clinical significance in plasma of patients with hepatitis C virus (HCV) genotype IV in the presence and absence of autoimmune extra hepatic manifestations in comparison to normal healthy individuals. Plasma Anti-C1q Abs levels were assessed by an Enzyme Linked Immunosorbant Assay in 91 chronic HCV-infected patients (51 with and 40 without autoimmune rheumatic manifestations) and 40 healthy volunteers matched for age and gender. Epidemiological, clinical, immunochemical and virological data were prospectively collected. Positive Anti-C1q antibodies were more frequent among HCV patients with extra-hepatic autoimmune involvement, than those without and healthy control subjects. No significant correlations were found between Anti-C1q levels with either the liver activity or the fibrosis scores. In HCV-patients with autoimmune involvements, plasma Anti-C1q levels were significantly higher in patients with positive cryoglobulin, and in those with lymphoma than in those without. These results were confirmed by multivariate analysis. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies among HCV infected patients with positive cryoglobulinaemia and lymphoma.
24261616 Rheumatoid arthritis disease activity and vitamin D deficiency in an Asian resident popula 2016 Apr AIM: We aimed to assess the prevalence of vitamin D deficiency and its association with rheumatoid arthritis (RA) disease activity in a UAE population. METHODS: Forty-five consecutive subjects were prospectively recruited during the early summer with their clinical examination and Health Assessment Questionnaire (HAQ) being recorded at a clinic appointment, along with their blood sample being taken for the 25-hydroxyvitamin D (25(OH)D) total test. RESULTS: Thirty-five (76%) patients claimed to be exposed to sunlight for < 30 min daily. The prevalence of vitamin D insufficiency (20-30 ng/mL) and deficiency (< 20 ng/mL) was 36% and 29%, respectively. RA patients who exposed their hands and feet (29 ng/mL) or more (34 ng/mL) to the sunlight had serum vitamin D levels higher than those who exposed their hands alone (18 ng/mL) or less (19 ng/mL) (P < 0.05). The variations in vitamin D levels due to skin color did not reach significance. No significant correlation was seen between serum vitamin D levels and Disease Activity Score (DAS28) or HAQ scores. A direct relationship was observed between HAQ scores and DAS28 scores (P < 0.05). CONCLUSION: We highlight the importance of skin exposure to sunlight in a conservative dressing culture. No association was observed between vitamin D and disease activity. However, the high prevalence of vitamin D deficiency may negatively impact on bone health of these patients in the future.
27509834 Bone-density testing interval and transition to osteoporosis in patients with rheumatoid a 2017 Jan The study aims to evaluate the rate of transition to osteoporosis in 360 RA patients and estimate the rescreening intervals of bone mineral density (BMD) testing. Osteoporosis was newly developed in 24.8 % during mean follow-up of 7.4 years. The estimated time of a BMD testing interval was dependent on the baseline T-score in RA patients. INTRODUCTION: Although BMD testing is routinely performed in RA patients, the interval between BMD tests has not been determined. METHODS: We retrospectively recruited 360 consecutive female patients with RA, who underwent repeated BMD testing, with a mean age of 53.7 ± 10.2 years and a mean follow-up duration of 7.4 ± 5.0 years. We stratified the study participants into five groups based on their baseline T-score range. The testing interval was defined as the estimated time for 10 % of patients in each subgroup to transition to osteoporosis. Competing-risk analyses were performed with sensitivity analysis by menopausal status and risk factors for transition to osteoporosis. RESULTS: At baseline, 15 % of screened patients had osteoporosis, and during follow-up, that proportion increased to 24.8 %. The estimated BMD testing interval for 10 % of patients to develop osteoporosis was 9.6 years for those with normal BMD, 7.6 years for those with mild osteopenia, 4.7 years for those with moderate osteopenia, and 2.1 years for those with severe osteopenia. No significant risk factor for transition to osteoporosis was identified in this cohort. CONCLUSIONS: Our data indicate that osteoporosis will develop in less than 10 % of female RA patients during rescreening intervals of approximately 9 years for those with normal bone density at baseline, 7 years for those with mild osteopenia, 4 years for those with moderate osteopenia, and 2 years for those with severe osteopenia at baseline. BMD interval in RA patients could be adjusted according to their baseline BMD T-scores.
28009092 Arthritis management in primary care - A study of physiotherapists' current practice, educ 2017 Dec BACKGROUND: With an increasing number of patients with osteoarthritis (OA) and rheumatoid arthritis (RA) in primary care, our aim was to investigate arthritis-related practice in physiotherapy and to study adherence to evidence-based care. METHODS: Seventy physiotherapists (PTs) working in primary care were emailed a questionnaire to investigate current practice and the number of roles assumed by PTs, the degree of confidence, educational needs and adherence to national guidelines in managing patients with OA or RA. Interventions supported by national guidelines were compared with reports of treatment modalities in the questionnaire. RESULTS: Sixty-four (91%) PTs responded, and they reported a higher degree of confidence in assessment, treatment and education of patients with OA than for those with RA (p < 0.001). The total number of roles assumed by the PTs was higher in the management of OA than for RA (p < 0.001). PTs who assumed a greater number of roles also reported a stronger degree of confidence in assessing OA (p = 0.036). Those who assumed fewer roles also reported less confidence in RA treatment (p = 0.045). Recommendations in the guidelines were followed by the majority of PTs for eight of 11 treatment modalities in OA and for six of six in RA. CONCLUSIONS: PTs reported a lower degree of confidence and the assumption of fewer roles in managing patients with RA compared with OA. There was good adherence to the national guidelines for almost all the treatment modalities listed. Even so, the results indicate a need for education, especially in chronic inflammatory arthritis care.
25912557 Elevated circulating Th17 and follicular helper CD4(+) T cells in patients with rheumatoid 2015 Aug It remains not fully elucidated the potential functions of Th17 cells and follicular helper T (Tfh) cells and secreting cytokines in the pathogenesis of rheumatoid arthritis (RA) and their association with disease activity. In this study, the frequencies of Th17 and Tfh cells were determined by flow cytometry, and the levels of interleukin (IL)-17, IL-21, and IL-22 were measured by ELISA in RA patients with different disease activities. The dynamic changes of cell subsets were also detected in response to disease-modify antirheumatic drugs (DMARDs) therapy. The percentages of CD3(+) CD4(+) IL-17A(+) (Th17) cells and CD3(+) CD4(+) CXCR5(+) ICOS(high) (Tfh) cells, as well as the concentrations of IL-17, IL-21, and IL-22 were significantly elevated in RA patients than those in healthy individuals. Furthermore, Tfh cells, IL-21, and IL-22 in the serum was positively correlated with the values of disease activity score. Concentrations of IL-21 and IL-22 in the serum were remarkably reduced following the DMARDs therapies. Our data suggested that Th17 cells, Tfh cells as well as the secreting cytokines may be involved in the pathogenesis of RA. The frequency of circulating Tfh cells and the productions of IL-21 and IL-22 were associated with the disease activity of RA patients, and might be potential therapeutic targets for treatment of RA.
26628605 Patients with Rheumatoid Arthritis have Similar Excellent Outcomes after Total Knee Replac 2016 Jan OBJECTIVE: Although new treatments for rheumatoid arthritis (RA) are extremely effective in preventing disease progression, rates of total knee replacement (TKR) continue to rise. The ongoing need for TKR is problematic, especially as functional outcomes in patients with RA have been reported to be worse than in patients with osteoarthritis (OA). The purpose of this study is to assess pain, function, and quality of life 2 years after TKR in contemporary patients with RA compared with patients with OA. METHODS: Primary TKR cases enrolled between May 1, 2007 and July 1, 2010 in a single institution TKR registry were eligible for this study. Validated RA cases were compared with OA at baseline and at 2 years. RESULTS: We identified 4456 eligible TKR, including 136 RA. Compared with OA, RA TKR had significantly worse preoperative Western Ontario and McMaster Universities Osteoarthritis Index pain (55.9 vs 46.6, p < 0.0001) and function (58.7 vs 47.3, p < 0.0001); however, there were no differences at 2 years. Within RA, there was no difference for patients who were treated with biologic disease-modifying antirheumatic drugs versus those who did not in pain (p = 0.41) or function (p = 0.39) at 2 years. In a multivariate regression, controlling for multiple potential confounders, there was no independent association of RA with 2-year pain (p = 0.18) or function (p = 0.71). Satisfaction was high for both RA and OA. CONCLUSION: Patients with RA undergoing primary TKR have excellent 2-year outcomes, comparable with OA, in spite of worse preoperative pain and function. In this contemporary cohort, RA is not an independent risk factor for poor outcomes.
27342690 Polymorphisms in STAT-4, IL-10, PSORS1C1, PTPN2 and MIR146A genes are associated different 2016 Nov Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in chronic inflammation of the synovium and consequent cartilage and bone erosion. RA is associated strongly with the presence of rheumatoid factor (RF), and consists of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and -negative patients. This study was designed to evaluate whether relevant single nucleotide polymorphisms (SNPs) associated with RA and other autoimmune disorders are related to RF, ACPA and clinical phenotype in a cohort of biologic drugs naive Italian RA patients; 192 RA patients and 278 age-matched healthy controls were included. Clinical and laboratory data were registered. We analysed a total of 12 single nucleotide polymorphisms (SNPs) in signal transducer and activator of transcription-4 (STAT-4), interleukin (IL)-10, psoriasis susceptibility 1 candidate 1 (PSORS1C1), protein tyrosine phosphatase, non-receptor type 2 (PTPN2), endoplasmic reticulum aminopeptidase 1 (ERAP1), tumour necrosis factor receptor-associated 3 interacting protein 2 (TRAF3IP2) and microRNA 146a (MIR146A) genes by allelic discrimination assays. Case-control association studies and genotype/phenotype correlation analyses were performed. A higher risk to develop RA was observed for rs7574865 in the STAT-4 gene, while the rs1800872 in the IL-10 gene showed a protective effect. The presence of RF was associated significantly with rs1800872 variant in IL-10, while rs2910164 in MIR146A was protective. ACPA were associated significantly with rs7574865 in STAT-4. The SNP rs2233945 in the PSORS1C1 gene was protective regarding the presence of bone erosions, while rs2542151 in PTPN2 gene was associated with joint damage. Our results confirm that polymorphisms in STAT-4 and IL-10 genes confer susceptibility to RA. For the first time, we described that SNPs in PSORS1C1, PTPN2 and MIR146A genes were associated differently with a severe disease phenotype in terms of autoantibody status and radiographic damage in an Italian RA population.
26482574 Effects of Person-Centered Physical Therapy on Fatigue-Related Variables in Persons With R 2016 Jan OBJECTIVE: To examine effects of person-centered physical therapy on fatigue and related variables in persons with rheumatoid arthritis (RA). DESIGN: Randomized controlled trial. SETTING: Hospital outpatient rheumatology clinic. PARTICIPANTS: Persons with RA aged 20 to 65 years (N=70): intervention group (n=36) and reference group (n=34). INTERVENTIONS: The 12-week intervention, with 6-month follow-up, focused on partnership between participant and physical therapist and tailored health-enhancing physical activity and balancing life activities. The reference group continued with regular activities; both groups received usual health care. MAIN OUTCOME MEASURES: Primary outcome was general fatigue (visual analog scale). Secondary outcomes included multidimensional fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire) and fatigue-related variables (ie, disease, health, function). RESULTS: At posttest, general fatigue improved more in the intervention group than the reference group (P=.042). Improvement in median general fatigue reached minimal clinically important differences between and within groups at posttest and follow-up. Improvement was also observed for anxiety (P=.0099), and trends toward improvements were observed for most multidimensional aspects of fatigue (P=.023-.048), leg strength/endurance (P=.024), and physical activity (P=.023). Compared with the reference group at follow-up, the intervention group improvement was observed for leg strength/endurance (P=.001), and the trends toward improvements persisted for physical (P=.041) and living-related (P=.031) aspects of fatigue, physical activity (P=.019), anxiety (P=.015), self-rated health (P=.010), and self-efficacy (P=.046). CONCLUSIONS: Person-centered physical therapy focused on health-enhancing physical activity and balancing life activities showed significant benefits on fatigue in persons with RA.
27749236 Decrease in articular hypoxia and synovial blood flow at early time points following infli 2016 Nov OBJECTIVES: An important feature of rheumatoid arthritis (RA) is hypoxia-driven synovial angiogenesis, but the relationship between change in vascularity, as measured by power Doppler ultrasound (PDUS), and oxygen tensions is unaddressed. METHODS: Metacarpophalangeal (MCP) joint PDUS was assessed in 23 patients with RA, alongside arthroscopic synovitis and oxygen tension measurements, at baseline and 4 weeks after anti-tumour necrosis factor (TNF) inhibitors. RESULTS: Anti-TNF reduced PDUS scores, which were negatively correlated with rise in oxygen tensions. The latter was related to good EULAR response at week 52. CONCLUSIONS: Anti-TNF results in rapid reduction in synovial blood flow, with a corresponding rise in oxygen tension most marked in EULAR good responders.
25701521 Sonographic cutoff values for detection of abnormalities in small, medium and large joints 2015 Apr To determine ultrasound measurements indicative of abnormalities in small, medium and large joints, we conducted a cross-sectional study comparing 60 patients with rheumatoid arthritis (RA) and 78 healthy volunteers. A MyLab 60 ultrasound machine (Esaote) and a linear multifrequency probe were used. Quantitative measurements of synovial recesses and semiquantitative measurements of synovial hyperplasia, power Doppler and bone erosion (scores = 0-3) were performed. The cutoff values for synovial recesses indicating RA (receiver operating characteristic curve, area under the curve >0.800) were found to be (radiocarpal) 3.78 mm and (ulnocarpal) 3.07 mm. Those measurements with the greatest chance of indicating RA (logistic regression analysis expressed as odds ratios [ORs]) were (p < 0.001) measurements of synovial hyperplasia (ulnocarpal, OR = 100, and radiocarpal, OR = 70); synovial power Doppler (radiocarpal, OR = 66); synovial bone erosion (radiocarpal, OR = 324); fifth metatarsophalangeal joint (OR = 100); and second metacarpophalangeal joint (OR = 92). We concluded that for both quantitative and semiquantitative ultrasound measurements, radiocarpal abnormalities increase the chance of detecting RA.
26737419 User-centric design of a personal assistance robot (FRASIER) for active aging. 2015 We present our preliminary results from the design process for developing the Worcester Polytechnic Institute's personal assistance robot, FRASIER, as an intelligent service robot for enabling active aging. The robot capabilities include vision-based object detection, tracking the user and help with carrying heavy items such as grocery bags or cafeteria trays. This work-in-progress report outlines our motivation and approach to developing the next generation of service robots for the elderly. Our main contribution in this paper is the development of a set of specifications based on the adopted user-centered design process, and realization of the prototype system designed to meet these specifications.
24412895 A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or wit 2015 May OBJECTIVES: To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis (ERA), and whether adalimumab provides an additional effect. METHODS: In a double-blind, placebo-controlled trial, 85 disease-modifying antirheumatic drug-naïve patients with ERA were randomised to receive methotrexate, intra-articular glucocorticosteroid injections and placebo/adalimumab (43/42). Contrast-enhanced MRI of the right hand was performed at months 0, 6 and 12. Synovitis, osteitis, tenosynovitis, MRI bone erosion and joint space narrowing (JSN) were scored with validated methods. Dynamic contrast-enhanced MRI (DCE-MRI) was carried out in 14 patients. RESULTS: Synovitis, osteitis and tenosynovitis scores decreased highly significantly (p<0.0001) during the 12-months' follow-up, with mean change scores of -3.7 (median -3.0), -2.2 (-1) and -5.3 (-4.0), respectively. No overall change in MRI bone erosion and JSN scores was seen, with change scores of 0.1 (0) and 0.2 (0). The tenosynovitis score at month 6 was significantly lower in the adalimumab group, 1.3 (0), than in the placebo group, 3.9 (2), Mann-Whitney: p<0.035. Furthermore, the osteitis score decreased significantly during the 12-months' follow-up in the adalimumab group, but not in the placebo group, Wilcoxon: p=0.001-0.002 and p=0.062-0.146. DCE-MRI parameters correlated closely with conventional MRI inflammatory parameters. Clinical measures decreased highly significantly during follow-up. CONCLUSIONS: A treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid in patients with ERA effectively decreased synovitis, osteitis and tenosynovitis and halted structural damage progression as judged by MRI. The findings suggest that addition of adalimumab is associated with further suppression of osteitis and tenosynovitis.
27444101 Further Simplification of the Simple Erosion Narrowing Score With Item Response Theory Met 2016 Aug OBJECTIVE: To further simplify the simple erosion narrowing score (SENS) by removing scored areas that contribute the least to its measurement precision according to analysis based on item response theory (IRT) and to compare the measurement performance of the simplified version to the original. METHODS: Baseline and 18-month data of the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial were modeled using longitudinal IRT methodology. Measurement precision was evaluated across different levels of structural damage. SENS was further simplified by omitting the least reliably scored areas. Discriminant validity of SENS and its simplification were studied by comparing their ability to differentiate between the COBRA and sulfasalazine arms. Responsiveness was studied by comparing standardized change scores between versions. RESULTS: SENS data showed good fit to the IRT model. Carpal and feet joints contributed the least statistical information to both erosion and joint space narrowing scores. Omitting the joints of the foot reduced measurement precision for the erosion score in cases with below-average levels of structural damage (relative efficiency compared with the original version ranged 35-59%). Omitting the carpal joints had minimal effect on precision (relative efficiency range 77-88%). Responsiveness of a simplified SENS without carpal joints closely approximated the original version (i.e., all Δ standardized change scores were ≤0.06). Discriminant validity was also similar between versions for both the erosion score (relative efficiency = 97%) and the SENS total score (relative efficiency = 84%). CONCLUSION: Our results show that the carpal joints may be omitted from the SENS without notable repercussion for its measurement performance.
26174438 Guided Imagery for Arthritis and Other Rheumatic Diseases: A Systematic Review of Randomiz 2015 Oct Many individuals suffering from arthritis and other rheumatic diseases (AORD) supplement pharmacologic treatments with psychosocial interventions. One promising approach, guided imagery, has been reported to have positive results in randomized controlled trials (RCTs) and is a highly scalable treatment for those with AORD. The main purpose of this study was to conduct a systematic review of RCTs that have examined the effects of guided imagery on pain, function, and other outcomes such as anxiety, depression, and quality of life in adults with AORD. Ten electronic bibliographic databases were searched for reports of RCTs published between 1960 and 2013. Selection criteria included adults with AORD who participated in RCTs that used guided imagery as a partial or sole intervention strategy. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Instrument. Results were synthesized qualitatively. Seven studies representing 306 enrolled and 287 participants who completed the interventions met inclusion criteria. The average age of the participants was 62.9 years (standard deviation = 12.2). All interventions used guided imagery scripts that were delivered via audio technology. The interventions ranged from a one-time exposure to 16 weeks in duration. Risk of bias was low or unclear in all but one study. All studies reported statistically significant improvements in the observed outcomes. Guided imagery appears to be beneficial for adults with AORD. Future theory-based studies with cost-benefit analyses are warranted.
25483913 Increased expression of endocan in arthritic synovial tissues: effects of adiponectin on t 2015 Apr This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, was increased in rheumatoid arthritic tissues. In addition, the involvement of adiponectin in the regulation of endocan expression in arthritic joints was examined. Arthritic synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) were immunostained with antibodies to endocan and vascular endothelial growth factor (VEGF). Subsequently, synovial cells and human umbilical vein endothelial cells were cultured and stimulated with interleukin-1 β (IL-1β) or adiponectin. The mRNA and protein levels of endocan were evaluated by polymerase chain reaction and ELISA, respectively. Endocan expression was markedly increased in the inflammatory sites of RA synovial tissues. In OA tissues, endocan expression was higher in tissues displaying moderate and severe inflammation than in those with mild inflammation. In vitro expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1β stimulation. Adiponectin was a more potent stimulant of endocan than IL-1β at their respective physiological concentrations in synovial cells. Endocan silencing by small interfering RNA transfection of synovial cells decreased in vitro cell migration and invasion. In conclusion, adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints.
27098050 GITRL is associated with increased autoantibody production in patients with rheumatoid art 2016 Sep The study aimed to determine the serum level of glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) in patients with rheumatoid arthritis (RA) and investigate its clinical significance. GITRL levels were measured by enzyme-linked immunosorbent assay (ELISA) in 88 RA patients, 20 osteoarthritis (OA) patients, and 20 healthy controls (HCs). Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were also tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies and the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The disease activity was evaluated by the 28-joint count Disease Activity Score (DAS28). GITRL concentrations were significantly elevated in both serum and synovial fluid (SF) of RA patients. GITRL levels in RA sera were significantly higher than those in matched SFs. Positive correlations were found between serum GITRL levels and inflammation parameters or autoantibody production. GITRL levels are significantly elevated in RA serum and SF and are positively correlated with autoantibody production in RA, suggesting a role of GITRL in the development of RA.
26254548 Predictive factors for induction of remission in patients with active rheumatoid arthritis 2016 Feb OBJECTIVE: To identify predictors of early response to tocilizumab (TCZ) in patients with active rheumatoid arthritis (RA) seen in daily routine clinical practice. METHODS: A multicenter ambispective observational study of 126 RA patients treated with TCZ as a first- or second-line biological therapy. The variables associated to achieve the therapeutic goal (remission defined as a DAS28-ESR < 2.6) at 3 and 6 months were identified using regression analysis. RESULTS: TCZ was administered as the first biologic in 26% of patients. Overall, 34% of patients received TCZ as monotherapy. EULAR response and remission were obtained in 82% and 31% of patients at 3 months and in 86% and 40% at 6 months. In the multivariate analysis, the predictive factors increasing the likelihood of clinical remission at 3 months were baseline ESR > 30 mm/h (OR = 19.07, 95% CI: 2.720-133.716), baseline CRP > 10 mg/L (OR = 4.95; 95% CI: 1.464-13.826), and the presence of extra-articular manifestations of the disease (OR = 15.45, 95% CI: 2.334-102.319). The factors that decreased it were higher concentrations of hemoglobin (OR = 0.53, 95% CI: 0.319-0.910), higher baseline DAS28-ESR (OR = 0.30, 95% CI: 0.145-0.635) and the number of previous DMARDs (OR = 0.41, 95% CI: 0.221-0.779), and biological therapies used (OR = 0.33, 95% CI: 0.155-0.734). The only factor that remained statistically significant at 6 months was higher baseline DAS28-ESR (OR = 0.55, 95% CI: 0.347-0.877). No relationship was found with the neutrophil count or with the RF or ACPA positivity. CONCLUSION: In routine clinical practice, strong acute phase response, the presence of extra-articular manifestations, and the number of previous DMARDs and biological therapies used may help to identify patients who will have a rapid response to TCZ. However, it is likely that no parameter will predict response if taken separately.
26464678 Immunolocalization of membrane-type 1 MMP in human rheumatoid synovium tissues. 2015 Membrane-type 1 matrix metalloproteinase (MT1-MMP, also known as MMP14), the best characterized membrane-anchored MMP, is an important matrix-degrading proteinase that could digest a broad spectrum of extracellular matrix proteins and accelerate angiogenesis. We have previously reported that some MMPs involved in the angiogenesis and the pannus formation within the joint, leading to the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). In the present study, we used immunohistochemistry assay and con-focal scanning technique to study the detailed immunolocalization of MT1-MMP in human RA synovium tissues as well as the infiltrating immune cell subsets. Our results showed that the positive MT1-MMP immunostaining could be found in synoviocytes, vascular endothelial cells, infiltrating macrophages and monocytes in RA synovium tissues, while weak or negative immunostaining could be found in infiltrating T cells, B cells and NK cells, respectively. Moreover, the Ki-67(+) highly proliferating synoviocytes also showed higher MT1-MMP expression in RA synoviocytes. Thus, the aberrant expression of MT1-MMP in RA synoviocytes as well as infiltrating immune cells may contribute to the proliferation of the synoviocytes, and the angiogenesis and the pannus formation in RA pathological progression.
26163397 Synovial fibroblasts integrate inflammatory and neuroendocrine stimuli to drive rheumatoid 2015 Rheumatoid arthritis is a chronic inflammatory disease that is characterized by pannus tissue consisting of synovial fibroblasts (SF), macrophages and lymphocytes. The inflammatory milieu in the joint activates resident SF and transforms them in a tumor-like phenotype. These changes manifest in resistance to Fas-induced apoptosis and production of cytokines, chemokines and matrix metalloproteinases. By alterations in DNA methylation, SF retain their transformed phenotype even in the absence of pro-inflammatory stimuli and are able to spread arthritis to unaffected joints. Furthermore, SF integrate neuroendocrine input to modulate inflammation since they possess receptors for several neurotransmitters (e.g., dopamine, norepinephrine and glutamate). Until now, no specific therapy targeting SF is available; however, reprogramming them to a regulatory phenotype might limit joint destruction and cartilage degradation.
24764451 Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gen 2015 Aug OBJECTIVES: Bruton's tyrosine kinase (Btk) is required for B lymphocyte and myeloid cell contributions to pathology in murine models of arthritis. Here, we examined the potential contributions of synovial Btk expression and activation to inflammation in rheumatoid arthritis (RA). MATERIALS AND METHODS: Btk was detected by immunohistochemistry and digital image analysis in synovial tissue from biologically naive RA (n=16) and psoriatic arthritis (PsA) (n=12) patients. Cell populations expressing Btk were identified by immunofluorescent double labelling confocal microscopy, quantitative (q-) PCR and immunoblotting. The effects of a Btk-specific inhibitor, RN486, on gene expression in human macrophages and RA synovial tissue explants (n=8) were assessed by qPCR, ELISA and single-plex assays. RESULTS: Btk was expressed at equivalent levels in RA and PsA synovial tissue, restricted to B lymphocytes, monocytes, macrophages and mast cells. RN486 significantly inhibited macrophage IL-6 production induced by Fc receptor and CD40 ligation. RN486 also reduced mRNA expression of overlapping gene sets induced by IgG, CD40 ligand (CD40L) and RA synovial fluid, and significantly suppressed macrophage production of CD40L-induced IL-8, TNF, MMP-1 and MMP-10, LPS-induced MMP-1, MMP-7 and MMP-10 production, and spontaneous production of IL-6, PDGF, CXCL-9 and MMP-1 by RA synovial explants. CONCLUSIONS: Btk is expressed equivalently in RA and PsA synovial tissue, primarily in macrophages. Btk activity is needed to drive macrophage activation in response to multiple agonists relevant to inflammatory arthritis, and promotes RA synovial tissue cytokine and MMP production. Pharmacological targeting of Btk may be of therapeutic benefit in the treatment of RA and other inflammatory diseases.