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ID PMID Title PublicationDate abstract
29278210 Biologics in Inflammatory and Immunomediated Arthritis. 2017 BACKGROUND: Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. METHODS: Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases. RESULTS: There are currently seven classes of biologics that are available for the treatment of inflammatory arthritis, each inhibiting a different aspect of the immune-driven inflammatory pathway. They include: • Tumor Necrosis Factor (TNF) inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol); • Interleukin-1 (IL-1) receptor antagonists (anakinra); • Interleukin-6 (IL-6) inhibition (tocilizumab); • Interleukin-12/23 (IL23) inhibition (ustekinumab); • Interleukin-17 (IL-17) inhibition (secukinumab); • B-cell inhibition (anti-CD20, rituximab); • T-cell costimulation inhibition (anti-CTLA-4, abatacept). CONCLUSION: In this review, we will focus on the role of biologic drugs in the treatment strategies for inflammatory arthritis.
28488248 Response to Treatment with TNFα Inhibitors in Rheumatoid Arthritis Is Associated with Hig 2017 Oct Biologic TNFα inhibitors are a mainstay treatment option for patients with rheumatoid arthritis (RA) refractory to other treatment options. However, many patients either do not respond or relapse after initially responding to these agents. This study was carried out to identify biomarkers that can distinguish responder from non-responder patients before the initiation of treatment. The level of cytokines in plasma and those produced by ex vivo T cells, B cells and monocytes in 97 RA patients treated with biologic TNFα inhibitors was measured before treatment and after 1 and 3 months of treatment by multiplex analyses. The frequency of T cell subsets and intracellular cytokines were determined by flow cytometry. The results reveal that pre-treatment, T cells from patients who went on to respond to treatment with biologic anti-TNFα agents produced significantly more GM-CSF than non-responder patients. Furthermore, immune cells from responder patients produced higher levels of IL-1β, TNFα and IL-6. Cytokine profiling in the blood of patients confirmed the association between high levels of GM-CSF and responsiveness to biologic anti-TNFα agents. Thus, high blood levels of GM-CSF pre-treatment had a positive predictive value of 87.5% (61.6 to 98.5% at 95% CI) in treated RA patients. The study also shows that cells from most anti-TNFα responder patients in the current cohort produced higher levels of GM-CSF and TNFα pre-treatment than non-responder patients. Findings from the current study and our previous observations that non-responsiveness to anti-TNFα is associated with high IL-17 levels suggest that the disease in responder and non-responder RA patients is likely to be driven/sustained by different inflammatory pathways. The use of biomarker signatures of distinct pro-inflammatory pathways could lead to evidence-based prescription of the most appropriate biological therapies for different RA patients.
28256202 Intralymphatic Histiocytosis: A Report of 2 Cases. 2018 Jan Intralymphatic histiocytosis is a benign condition characterized by poorly defined erythematous plaques (sometimes forming a reticular pattern) as well as the presence of nodules and vesicles. Its etiology and pathogenesis appear to be related to chronic inflammation in the affected area, prior surgery, or systemic disease, particularly rheumatoid arthritis. We report on 2 new cases, both associated with joint surgery in the affected area and osteoarticular disease (primary synovial osteochondromatosis and rheumatoid arthritis). This is a chronic disease and there is no specific treatment. Different treatment options were chosen in the 2 cases described. A spectacular response to treatment with oral pentoxifylline and topical tacrolimus was observed in 1 of the patients.
28221313 Systematic Review and Meta-analysis of Interventions for Depression and Anxiety in Persons 2017 Dec BACKGROUND: Psychiatric comorbidities, such as depression and anxiety, are very common in persons with rheumatoid arthritis (RA) and can lead to adverse outcomes. By appropriately treating these comorbidities, disease-specific outcomes and quality of life may be improved. OBJECTIVE: The aim of this study was to systematically review the literature from controlled trials of treatments for depression and anxiety in persons with RA. METHODS: We searched multiple online databases from inception until March 25, 2015, without restrictions on language, date, or location of publication. We included controlled trials conducted in persons with RA and depression or anxiety. Two independent reviewers extracted information including trial and participant characteristics. The standardized mean differences (SMDs) of depression or anxiety scores at postassessment were pooled between treatment and comparison groups, stratified by active versus inactive comparators. RESULTS: From 1291 unique abstracts, we included 8 RA trials of depression interventions (6 pharmacological, 1 psychological, 1 both). Pharmacological interventions for depression with inactive comparators (n = 3 trials, 143 participants) did not reduce depressive symptoms (SMD, -0.21; 95% confidence interval [CI], -1.27 to 0.85), although interventions with active comparators (n = 3 trials, 190 participants) did improve depressive symptoms (SMD, -0.79; 95% CI, -1.34 to -0.25). The single psychological trial of depression treatment in RA did not improve depressive symptoms (SMD, -0.44; 95% CI, -0.96 to 0.08). Seven of the trials had an unclear risk of bias. CONCLUSIONS: Few trials examining interventions for depression or anxiety in adults with RA exist, and the level of evidence is low to moderate because of the risk of bias and small number of trials.
28455827 Characteristics and risk factors of lymphoproliferative disorders among patients with rheu 2017 Jun The purpose of the study is to demonstrate the characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA) and risk factors for LPD among RA patients concurrently treated with methotrexate (MTX). Among patients who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study in October 2010, past existence of LPD from patient's report was confirmed through medical charts. Background factors, LPD pathological findings, and the clinical courses of LPD and RA after LPD were assessed. To analyze the risk of MTX-associated LPD among RA patients concurrently treated with MTX, a nested case-control study design was used to select control patients who had received MTX but did not develop LPD by matching calendar date, sex, and age (within 5 years) at a 1:10 ratio. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for occurrence of LPD were analyzed by multivariate analysis. Forty-eight patients experienced LPD among 5757 patients, and 25 (52.1%) of those had lymphoma. LPD regressed in 60.4% of all LPD patients and 24.0% of lymphoma patients. In the 26 cases who developed LPD during MTX treatment, multivariate analysis revealed that 28-joint disease activity score (DAS28) (OR 1.57 [95% CI, 1.12-1.57]; p < 0.01) and lactate dehydrogenase (LDH) level (OR 1.01 [95% CI, 1.00-1.02]; p < 0.01), but not concomitant dose of MTX, were risk factors for LPD. Among RA patients concomitantly treated with MTX, high disease activity, but not MTX dose, was a risk factor for the occurrence of LPD.
28676287 Analysis of effectiveness, safety and optimization of tocilizumab in a cohort of patients 2019 Jan OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. MATERIAL AND METHODS: Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier. RESULTS: The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. CONCLUSIONS: Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC.
28764705 Drug survival of second biological DMARD therapy in patients with rheumatoid arthritis: a 2017 Aug 2 BACKGROUND: Since persistence to first biological disease modifying anti-rheumatic drugs (bDMARDs) is far from ideal in rheumatoid arthritis (RA) patients, many do receive a second and/or third bDMARD treatment. However, little is known about treatment persistence of the second-line bDMARD and it is specifically unknown whether the mode of action of such a treatment is associated with different persistence rates. We aimed to assess discontinuation-, re-initiation- or continuation-rates of a 2nd bDMARD therapy as well as switching-rates to a third biological DMARD (3rd bDMARD) therapy in RA patients. METHOD: Analysis was based on German claims data (2010-2013). Patients were included if they had received at least one prescription for an anti-TNF and at least one follow-up prescription of a 2nd bDMARD different from the first anti-TNF. Patient follow-up started on the date of the first prescription for the 2nd bDMARD and lasted for 12 months or until a patient's death. RESULTS: 2667 RA patients received at least one anti-TNF prescription. Of these, 451 patients received a second bDMARD (340 anti-TNF, mean age 52.6 years; 111 non-anti-TNF, mean age 55.9 years). During the follow-up, 28.8% vs. 11.7% of the 2nd anti-TNF vs. non-anti-TNF patients (p < 0.001) switched to a 3rd bDMARD; 14.1% vs. 19.8% (p = 0.179) discontinued without re-start; 3.8% vs.1.8% (p = 0.387) re-started and 53.5 vs. 66.7% (p < 0.050) continued therapy. Patients in the non-anti-TNF group demonstrated longer drug survival (295 days) than patients in the anti-TNF group (264 days; p = 0.016). Independent variables associated with earlier discontinuation (including re-start) or switch were prescription of an anti-TNF as 2nd bDMARD (HR = 1.512) and a higher comorbidity level (CCI, HR = 1.112), whereas previous painkiller medication (HR = 0.629) was associated with later discontinuation or switch. CONCLUSIONS: Only 56.8% of RA patients continued 2nd bDMARD treatment after 12 months; 60% if re-start was included. Non-anti-TNF patients had a higher probability of continuing 2nd bDMARD therapy.
29142029 Routine Use of Quantitative Disease Activity Measurements among US Rheumatologists: Implic 2018 Jan OBJECTIVE: The aim of our study was to examine why real-world practices and attitudes regarding quantitative measurements of rheumatoid arthritis (RA) have received limited attention. METHODS: An e-mail survey asked US rheumatologists to self-report on their use of quantitative measurements (metric). RESULTS: Among 439 respondents, metric rheumatologists (58%) were more likely to be in group practice and to use tumor necrosis factor inhibitors. The quantitative tools most commonly used were the Health Assessment Questionnaire (35.5%) and the Routine Assessment of Patient Index Data 3 (27.1%). Reasons for not measuring included time needed and electronic availability. Based on simulated case scenarios, providing more quantitative information increased the likelihood that a patient would change to a different disease-modifying antirheumatic drug or biologic. CONCLUSION: Routine use of quantitative measurement for patients in the United States with RA is increasing over time but remains low.
28340012 Assessment of muscle mass relative to fat mass and associations with physical functioning 2017 Jun 1 OBJECTIVES: To determine whether a novel measure of appendicular lean mass relative to fat mass is associated with physical functioning in RA. METHODS: In a cross-sectional design, three independent RA cohorts were retrospectively analysed. Whole-body DXA measures of appendicular lean mass index (ALMI, kg/m 2 ) and fat mass index (FMI, kg/m 2 ) were converted to age, sex and race-specific Z-scores using published National Health and Nutrition Examination Survey reference ranges. Adiposity-adjusted ALMI Z-scores (ALMI FMI ) were determined using a published method to adjust for normal associations between ALMI and FMI Z-scores. Associations between ALMI Z-scores, ALMI FMI Z-scores and physical functioning were assessed after adjusting for age, sex and study. Functional outcomes assessed included the HAQ, Valued Life Activities assessment and Short Physical Performance Battery. Low lean for age was defined as a Z-score of -1 or less. RESULTS: Our sample consisted of 442 patients with RA. The combined cohort had a mean ALMI Z-score of - 0.51 (1.08) and a mean ALMI FMI Z-score of - 0.58 (1.53), suggesting muscle mass deficits compared with a nationally representative sample. Greater ALMI FMI Z-scores demonstrated stronger associations with better functional outcomes compared with ALMI Z-scores. Associations were not attenuated with adjustment for systemic inflammation or pain. The FMI Z-score was independently associated with physical functioning, with a stronger association seen among patients with greater FMI Z-score. Adiposity-adjusted definitions of low lean mass more clearly identified those with functional impairment. CONCLUSION: Estimates of appendicular lean mass that are adjusted for adiposity demonstrate stronger positive associations with functional outcomes compared with unadjusted estimates.
29272303 Aerobic capacity over 16 years in patients with rheumatoid arthritis: Relationship to dise 2017 The aim of this study was to analyse the change in aerobic capacity from disease onset of rheumatoid arthritis (RA) over 16.2 years, and its associations with disease activity and cardiovascular risk factors. Twenty-five patients (20 f/5 m), diagnosed with RA 1995-2002 were tested at disease onset and after mean 16.2 years. Parameters measured were: sub-maximal ergometer test for aerobic capacity, functional ability, self-efficacy, ESR, CRP and DAS28. At follow-up, cardiovascular risk factors were assessed as blood lipids, glucose concentrations, waist circumference, body mass index (BMI), body composition, pulse wave analysis and carotid intima-media thickness. Aerobic capacity [median (IQR)] was 32.3 (27.9-42.1) ml O2/kg x min at disease onset, and 33.2 (28.4-38.9) at follow-up (p>0.05). Baseline aerobic capacity was associated with follow-up values of: BMI (rs = -.401, p = .047), waist circumference (rs = -.498, p = .011), peripheral pulse pressure (rs = -.415, p = .039) self-efficacy (rs = .420, p = .037) and aerobic capacity (rs = .557, p = .004). In multiple regression models adjusted for baseline aerobic capacity, disease activity at baseline and over time predicted aerobic capacity at follow-up (AUC DAS28, 0-24 months; β = -.14, p = .004). At follow-up, aerobic capacity was inversely associated with blood glucose levels (rs = -.508, p = .016), BMI (rs = -.434, p = .030), body fat% (rs = -.419, p = .037), aortic pulse pressure (rs = -.405, p = .044), resting heart rate (rs = -.424, p = .034) and self-efficacy (rs = .464, p = .020) at follow-up. We conclude that the aerobic capacity was maintained over 16 years. High baseline aerobic capacity associated with favourable measures of cardiovascular risk factors at follow-up. Higher disease activity in early stages of RA predicted lower aerobic capacity after 16.2 years.
28472610 Nature, functions, and clinical implications of IgG4 autoantibodies in systemic lupus eryt 2017 Mar Protective autoantibodies in homeostasis, clinical relevance, and therapeutic potential have gained wide attention. Recent studies showed that IgG4 autoantibodies play crucial roles in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In one aspect, IgG4 autoantibodies can bind autoantigens in competition with other classes of immunoglobulins (e.g., IgG1, IgG2a) to form non-inflammatory immune-complexes (ICs), which have a limited ability to induce immune responses because of the low affinity of IgG4 for both Fc receptors and the C1 complement molecule, resulting in reduced inflammatory response in SLE and RA. In another aspect, the CH2 domain of IgG4, post antibody binding with autoantigens, might become a target for rheumatoid factors (RFs) in RA. The resultant bigger ICs containing RF-IgG4-autoantigens were shown to strongly induce immune responses and to cause tissue damage in RA. In addition, the roles of IgG4-IgG1 (IgG4-IgG2 or IgG4-IgG3)-complexes and bispecific IgG4 in SLE and RA are also reviewed. Overall, IgG4 autoantibodies may act as a monitor for the pathogenesis in SLE and RA and even as a treatment for SLE.
28888761 Associations Between TNFAIP3 Gene Polymorphisms and Rheumatoid Arthritis Risk: A Meta-anal 2017 May BACKGROUND AND AIMS: A host of studies investigated the associations between tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs2230926 and rs5029937 polymorphisms and rheumatoid arthritis (RA) susceptibility, but with conflicting findings. Therefore, we explored whether TNFAIP3 gene rs2230926 and rs5029937 polymorphisms are associated with RA by meta-analysis. MATERIAL AND METHODS: We performed out a comprehensive literature search of PubMed, Elsevier, Embase, and CNKI databases to identify relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: Literature search identified 10 case-control studies involving 18,014 cases and 20,112 controls in this meta-analysis. Our data supported an association between TNFAIP3 gene rs2230926 and rs5029937 polymorphisms and RA risk. Stratification analysis of ethnicity indicated that rs5029937 polymorphism increased the risk of RA among Caucasians, while rs2230926 polymorphism increased the risk of RA among Asians and Caucasians. CONCLUSIONS: In conclusion, this meta-analysis demonstrates that TNFAIP3 gene polymorphisms (rs2230926 and rs5029937) are associated with the increased risk of RA.
28600618 Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis. 2018 Jan Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.
27942735 Total Humeral Endoprosthesis Replacement to Salvage Periprosthetic Fractures in Rheumatoid 2017 Mar 1 The authors report their experience in the management of a 53-year-old woman with rheumatoid arthritis who presented with bilateral asynchronous traumatic periprosthetic fractures of the humerus after bilateral elbow replacements. One side was treated with a long-stem revision and internal fixation with bone graft, while the other side was treated with a long-stem distal humeral replacement. She sustained pathological periprosthetic fractures on top of the long-stemmed implants. Total humeral endoprosthesis replacements were performed bilaterally as salvage procedures to provide a stable platform for her elbow and hand function. At manuscript submission, the patient was 24 months and 36 months postoperatively on the left and right sides, respectively. Her Oxford Shoulder Scores were 21 (left side) and 24 (right side). There is little information about the management of periprosthetic fractures of the humerus after long-stem revisions with severe bone loss. To the best of the authors' knowledge, this is the first case report describing the use of bilateral total humeral endoprosthesis replacements in the management of complex unstable periprosthetic fractures. This is a valuable treatment option for patients with poor bone quality, bone loss, and loose components. [Orthopedics. 2017; 40(2):e363-e366.].
27591827 End-stage renal disease in patients with rheumatoid arthritis. 2017 Feb OBJECTIVES: To determine the frequency of end-stage renal disease (ESRD) in patients with rheumatoid arthritis (RA), the causes of ESRD, and the treatment of RA in the setting of ESRD. METHODS: Cross-sectional study of RA (N = 3754) and non-RA (N = 326,776) patients in the United States Renal Data System (USRDS) during 2011 (N = 330,530). The epidemiology of ESRD in RA was determined and the etiology of ESRD in patients with and without RA was compared. The frequency of patients with RA with at least one filled prescription for prednisone/prednisolone, a DMARD, and/or a biologic in 2011 was determined. RESULTS: The prevalence of RA with ESRD in the USRDS in 2011 was 1.1%. There were significant differences in age, race, sex, and BMI category between the groups (p < 0.01). Diabetes (33.5%) and hypertension (30.6%) were the most common primary causes of ESRD in patients with RA. Amyloidosis, vasculitis, and analgesic nephropathy combined accounted for less than 10% of cases of ESRD. Prednisone was the most commonly filled medication that could be used to treat RA (45.9% of RA patients). Hydroxychloroquine was the most frequently filled DMARD (13.5%); biologics were uncommon (etanercept 2.5%, adalimumab 1.5%; golimumab, infliximab, anakinra, and abatacept <1%). CONCLUSIONS: The co-occurrence of RA with ESRD was 1.1% in the USRDS by 2011. Physicians should be aware of the critical impact of the comorbidities of diabetes and hypertension in causing ESRD in RA patients. Use of DMARDS other than hydroxychloroquine and biologics to treat RA in the setting of ESRD appears to be infrequent. Further prospective studies of treatment strategies for RA in ESRD are needed.
29281812 Dynamic joint stiffness of the ankle in healthy and rheumatoid arthritis post-menopausal w 2018 Feb The purpose of this study was to compare rheumatoid arthritis post-menopausal women (RAPW) with pathological involvement of the lower limb joints and age-matched healthy post-menopausal women (AHPW) in regard to the dynamic joint stiffness of the ankle (DJS(ankle)) during the stance phase of gait. Data were collected from 18 RAPW and 18 AHPW. Gait was assessed by a three-dimensional motion analysis system synchronised with a force plate. Subjects walked barefoot at natural and self-selected speed, performing 14 valid trials (comprising 7 left and 7 right foot-steps on a force plate). The stance phase was split into three sub-phases that corresponded to the three angular displacements of the ankle that occurred during this phase, namely, controlled plantar flexion (CPF), controlled dorsiflexion (CDF), and powered plantar flexion (PPF). A linear model represented each sub-phase and computed DJS(ankle). Model fitting was assessed by the coefficient of determination (R(2)). The coefficient of variation (CV) was used to assess intra-individual variability. In all sub-phases, R(2) values for both groups were higher than 0.85. There were no differences in the R(2) values among groups. RAPW showed a higher DJS(ankle) during the CPF (p < 0.05). CDF and PPF yielded no differences among groups. During CPF, RAPW yielded a higher CV for DJS(ankle) (p < 0.01). RAPW also yielded lower ankle angular displacements during CPF and PPF (p < 0.05). Findings suggested that the stance phase of RAPW and AHPW can be studied by a linear ankle 'moment of force -- angle' relationship. During CPF, RAPW exhibited excessive ankle stiffness and presented a higher intra-individual DJS(ankle) variability.
28431485 Efficacy of golimumab in Belgian patients with active rheumatoid arthritis despite treatme 2017 Dec OBJECTIVES: The GO-MORE trial (NCT00975130) was a phase 3 study in 40 countries evaluating the efficacy and safety of golimumab as add-on therapy in biologic-naïve adults with active rheumatoid arthritis despite stable treatment with disease-modifying anti-rheumatic drugs. To inform local practice in Belgium and examine the role of baseline disease activity in treatment response, we compared the efficacy of golimumab in the Belgian subpopulation and the rest of the world. METHODS: Baseline disease activity and six-month efficacy rates in the GO-MORE trial were compared for the Belgian subpopulation and the rest of the world by t-tests and chi-squared tests. RESULTS: Except for functional impairment, all measures of baseline disease activity were significantly lower (p < 0.0001) in the Belgian population (n = 123) than in the rest of the world (n = 3157). At month six, the rate of good/moderate EULAR response was similar in Belgium and the rest of the world (78.9% vs. 82.2%; p = 0.34), but remission rates were higher in Belgium according to the DAS28-ESR (43.1% vs. 23.2%; p < 0.0001) and Simplified Disease Activity Index (22.0% vs. 13.8%; p = 0.01). Rates of low DAS28-ESR disease activity were also higher in Belgium (54.5% vs. 36.8%; p < 0.0001). Within the Belgian subpopulation, efficacy measures were not significantly different between patients with moderate (n = 73) and high baseline activity (n = 49). Rates of functional impairment at month six did not differ between the two populations. CONCLUSION: In the Belgian population of the GO-MORE trial, baseline disease activity was lower and six-month remission rates were higher than in the rest of the world.
28314879 A study on associations of single-nucleotide polymorphisms within H19 and HOX transcript a 2017 Jun OBJECTIVE: The purpose of our study was to examine whether the H19 rs2839698, rs217727, and HOX transcript antisense RNA (HOTAIR) rs12826786 polymorphisms were associated with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population. METHODS: A total of 777 participants were enrolled in this study, including 328 RA patients and 449 healthy controls. The H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms were detected by the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. RESULTS: No significant difference in genotype distribution between RA patients and healthy controls was found (P = 0.38 for rs2839698; P = 0.79 for rs217727; P = 0.39 for rs12826786). The difference in allele frequencies between RA patients and controls was also non-significant (rs2839698 T versus C, P = 0.23, odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.92-1.43; rs217727 C versus T, P = 0.55, OR = 1.07, 95% CI = 0.87-1.32; and rs12826786 T versus C, P = 0.32, OR = 1.14, 95% CI = 0.88-1.47). We have also evaluated the relationships of above-mentioned polymorphisms with risk of RA under dominant model and recessive model, but non-significant evidence was found. No significant evidence was detected for the relationships of H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms with risk of different serotypes of RA. CONCLUSIONS: Our results indicated that H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms might not be involved in the genetic background of RA in Chinese.
29303701 Increased levels of serum histone H4 and activated protein C in patients with active rheum 2018 May OBJECTIVES: We aimed to examine the levels of serum H4 and activated protein C (APC) in rheumatoid arthritis (RA) and other autoimmune conditions, and investigate the associations between H4 or APC levels and disease activity indicators in RA. METHODS: Serum H4 and APC distribution was examined in samples from patients with RA, systemic lupus erythematosus (SLE), polymyositis (PM), and ankylosing spondylitis (AS), as well as in samples from healthy controls, using commercial ELISA kits. Associations of serum H4 or APC levels with disease variables in patients with RA were evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminant capacity of APC against RA and non-RA. RESULTS: The patients with RA, PM, and AS showed higher serum levels of H4 and APC than those from the healthy control individuals, while the SLE patients showed higher serum levels of APC only. Moderate positive correlations between H4 levels and absolute neutrophil count (ANC), platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), brinogen (FIB), D-dimer (DD), and complement fraction 3 (C3) were observed. Positive correlations between APC levels and PLT, RF, DD, or DAS28 were additionally found. ROC curve analysis revealed that APC discriminated well between RA and non-RA. CONCLUSIONS: H4 and APC concentrations are elevated in patients with chronic in ammatory autoimmune diseases. The observed associations between H4 and APC and disease variables in patients with RA support a role for H4 and APC in the in ammatory process of the disease.
28079506 Response of human rheumatoid arthritis osteoblasts and osteoclasts to adiponectin. 2017 May OBJECTIVES: Adiponectin is an effector molecule in the pathophysiology of rheumatoid arthritis, e.g. by inducing cytokines and matrix degrading enzymes in synovial fibroblasts. There is growing evidence that adiponectin affects osteoblasts and osteoclasts although the contribution to the aberrant bone metabolism in rheumatoid arthritis is unclear. Therefore, the adiponectin effects on rheumatoid arthritis-derived osteoblasts and osteoclasts were evaluated. METHODS: Adiponectin and its receptors were examined in bone tissue. Primary human osteoblasts and osteoclasts were stimulated with adiponectin and analysed using realtime polymerase chain-reaction and immunoassays. Effects on matrix-production by osteoblasts and differentiation and resorptive activity of osteoclasts were examined. RESULTS: Immunohistochemistry of rheumatoid arthritis bone tissue showed adiponectin expression in key cells of bone remodelling. Adiponectin altered gene expression and cytokine release in osteoblasts and increased IL-8 secretion by osteoclasts. Adiponectin inhibited osterix and induced osteoprotegerin mRNA in osteoblasts. In osteoclasts, MMP-9 and tartrate resistant acid phosphatase expression was increased. Accordingly, mineralisation capacity of osteoblasts decreased whereas resorptive activity of osteoclasts increased. CONCLUSIONS: The results confirm the proinflammatory potential of adiponectin and support the idea that adiponectin influences rheumatoid arthritis bone remodelling through alterations in osteoblast and osteoclast.