Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
28079511 Circulating carotenoids and subsequent risk of rheumatoid arthritis in women. 2017 Mar OBJECTIVES: The aim of the present study was to examine the associations between circulating carotenoids and future risk of rheumatoid arthritis (RA). METHODS: We conducted a nested case-control study consisting of 227 incident RA cases and 671 matched controls with prospectively measured plasma carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin) levels in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Each incident RA case was matched with 3 healthy controls. Serologic phenotype of RA was determined by rheumatoid factor or anti-citrullinated peptide antibody (ACPA) obtained by chart review. Multivariable logistic regressions were used to estimate odds ratios (OR) and 95% confident intervals (95% CI) for RA risk associated with each circulating carotenoid after adjusting for matching factors and other covariates. RESULTS: The median time from blood draw until RA diagnosis was 8.6 years. In the multivariable models, no significant associations were found between any plasma carotenoids and risk of RA. We further examined the associations for two subtypes of RA, and found associations of circulating α-carotene and β-carotene with reduced risk of seronegative RA. After correction for multiple comparisons using the Bonferroni method, the findings did not reach statistical significance. CONCLUSIONS: Circulating carotenoids levels are not associated with reduced risk of RA. Further investigations using large prospective cohorts are needed to confirm our findings.
27435295 Prediction of the therapeutic response to methotrexate at 24 weeks by methotrexate-polyglu 2017 May OBJECTIVES: The objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of methotrexate-polyglutamates (MTX-PGs) in erythrocytes in patients with rheumatoid arthritis and correlate them with the efficacy. METHODS: MTX-PG concentrations in erythrocytes were measured in 42 MTX-naïve patients repeatedly for 24 weeks by high-performance liquid chromatography. In 56 patients receiving stable MTX doses for at least 12 weeks, the correlation between MTX doses and MTX-PG concentrations was examined. The efficacy was measured by the change of DAS28CRP (ΔDAS28CRP). RESULTS: There were moderate correlations between MTX dose and MTX-PG 3, 4, and 5. At 24 weeks, MTX-PG2, 3, 4, and 1-5 were higher in patients with ΔDAS28CRP >1.2 than in those with ≤1.2. The cutoff value of MTX-PG1-5 to discriminate ΔDAS28CRP >1.2 from ≤1.2 at 24 weeks was 68.7 nM. Among 20 patients with MTX-PG1-5 > 50.6 nM at 8 weeks, seven already improved at 8 weeks and additional 11 improved at 24 weeks (p < 0.001). On the contrary, among the nine patients with MTX-PG1-5 ≤ 50.6 nM at 8 weeks, none improved at 8 weeks and only one improved at 24 weeks (p = 0.500). CONCLUSIONS: Erythrocyte MTX-PGs might be a potential indicator and predictor of MTX efficacy.
28967235 Addressing rural and remote access disparities for patients with inflammatory arthritis th 2018 Mar OBJECTIVE: The aim of the present study was to evaluate whether rheumatoid arthritis (RA) patients followed longitudinally using video-conferencing and inter-professional care support have comparable disease control to those followed in traditional in-person rheumatology clinics. METHODS: This was a randomized controlled trial for 85 RA patients allocated to either traditional in-person rheumatology follow-up or video-conferenced follow-up with urban-based rheumatologists and rural in-person physical therapist examiners. Follow-up was every 3 months for 9 months. Outcome measures included disease activity metrics (disease activity in 28 joints with CRP measure score [DAS28-CRP], and RA disease activity index [RADAI]), modified health assessment questionnaire (mHAQ), quality of life (EuroQOL five dimensions questionnaire [EQ5D]) and patient satisfaction (nine-item visit-specific satisfaction questionnaire [VSQ9]). RESULTS: Of 85 participants, 54 were randomized to the video-conferencing team model and 31 to the traditional clinic (control group). Dropout rates were high, with only 31 (57%) from the video-conferencing and 23 (74%) from the control group completing the study. The mean age for study participants was 56 years; 20% were male. Mean RA disease duration was 13.9 years. There were no significant between-group differences in DAS28-CRP, RADAI, mHAQ or EQ5D scores at baseline or over the study period. Satisfaction rates were high in both groups. CONCLUSIONS: We found no evidence of a difference in effectiveness between inter-professional video-conferencing and traditional rheumatology clinic for both the provision of effective follow-up care and patient satisfaction for established RA patients. High dropout rates reinforce the need for consultation with patients' needs and preferences in developing models of care. While use of video-conferencing/telehealth technologies may be a distinct advantage for some patients, there may be loss of travel-related auxiliary benefits for others.
28485187 Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etan 2018 Jan OBJECTIVE: To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival. METHOD: We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital (1999-2008), of whom 16 had seronegative and 129 seropositive RA. TNF-α in serum was quantified using enzyme-linked immunosorbent assay in samples from the onset of treatment and at 6 week follow-up. Drug survival time was used to evaluate the long-term efficacy of etanercept. RESULTS: Levels of TNF-α were significantly increased at follow-up compared to at the start. At the 6 week follow-up, circulating TNF-α mainly comprised TNF-α in complex with etanercept. Longer drug survival time correlated with increased TNF-α at 6 week follow-up in the patients with seronegative RA, but not in the seropositive patients. CONCLUSION: We demonstrated that levels of circulating TNF-α increased in almost all individuals after initiation of treatment with etanercept and that this increase mainly comprised TNF-α in complex with etanercept. More importantly, this increase may predict drug survival in adults with seronegative, but not seropositive, RA and suggests that measuring TNF-α/etanercept complexes in serum may be relevant in patients with seronegative RA.
28682648 Kinase inhibitors of the IGF-1R as a potential therapeutic agent for rheumatoid arthritis. 2017 Aug We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro. Cell proliferation was evaluated by cell count and immunoblotting. The expression of IGF-1 and IGF-1 R was evaluated by RT-PCR. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay, and osteoclast-specific enzyme production. Angiogenesis was evaluated by a tube formation assay using human umbilical vein endothelial cells (HUVECs). The proliferation of MH7A cells was found to be inhibited in the presence of NVP-AEW541, and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was downregulated in MH7A cells. IGF-1 and IGF-1 R mRNA expression levels were upregulated during formation of M-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)-mediated osteoclast formation. Moreover, osteoclastogenesis was suppressed in the presence of NVP-AEW541. The formation of the tubular network was enhanced by IGF-1, and this effect was neutralized by NVP-ARE541. Our findings suggest that NVP-AEW541 may be utilized as a potential therapeutic agent in the treatment of RA.
28634103 Undetectable Mannose Binding Lectin and Corticosteroids Increase Serious Infection Risk in 2017 Nov BACKGROUND: Infection is the leading cause of death in rheumatoid arthritis (RA). Corticosteroid (CS) use is a known and important risk factor for serious infections (SIs). Mannose binding lectin (MBL) is a genetically determined component of the innate immune system implicated in neonatal infections. OBJECTIVE: Our aim was to determine whether MBL deficiency is a risk factor for SIs in RA and to compare it with CS use and also synthetic and biologic disease-modifying antirheumatic drug (DMARD) therapy. METHODS: Data on 228 patients with RA were collected for up to 7 years (median = 5.9 years). Serum MBL concentrations were determined in all patients receiving synthetic (n = 96) or biologic (n = 132) DMARD therapy. RESULTS: High rates of SIs were observed in RA irrespective of treatment (17%). Similar rates of SIs were observed in synthetic and biologic DMARD users. The rates of single and multiple SIs were similar, irrespective of the use of a biologic agent. Undetectable MBL (<56 ng/mL) concentrations and maintenance prednisolone at 10 mg per day or higher were associated with an increased risk for an SI, with incident risk ratio of 4.67 (P = .001) and 4.70 (P < .001), respectively. CONCLUSIONS: Undetectable MBL and prednisolone confer a high risk for an SI. The use of biologic DMARDs did not confer substantial SI risk in this observational study. MBL deficiency is hitherto an unrecognized risk factor for an SI in RA.
28859591 Assessing Implementation Readiness and Success of an e-Resource to Improve Prelicensure Ph 2017 Sep Study Design Prospective within-subject, cross-sectional, between-group, nested qualitative designs within an implementation science framework. Background Physical therapy is recommended for rheumatoid arthritis (RA) care, yet prelicensure RA curriculum time remains limited. Objectives To determine readiness for, and success of, implementing an e-learning tool, Rheumatoid Arthritis for Physiotherapists e-Learning (RAP-eL), within the prelicensure physical therapy curriculum. Methods All physical therapy students in a 1-year cohort in 2014 had RAP-eL embedded in their curriculum. Rheumatoid Arthritis for Physiotherapists e-Learning is an online platform that delivers RA disease information with translation to clinical practice. Implementation readiness, determined by acceptability of RAP-eL to students, was evaluated using focus groups (n = 23). Implementation success was measured using quantitative data from a previously validated questionnaire, including changes in students' self-reported confidence in knowledge (out of 45) and skills (out of 40) in managing RA after 4 weeks of access to RAP-eL, retention of learning over 14 months, and differences in workforce readiness between students in the cohort who had access to RAP-eL and a historical control cohort. Results Acceptability of RAP-eL was confirmed from qualitative data, demonstrating implementation readiness. Short-term improvements were observed in RA knowledge (mean difference, 16.6; 95% confidence interval [CI]: 15.7, 17.6) and RA skills (mean difference, 14.9; 95% CI: 13.9, 15.9; n = 137). Retention was demonstrated after 14 months (P<.001; n = 62). Students in the 1-year cohort who had RAP-eL embedded in the curriculum scored significantly higher on knowledge (mean difference, 3.6; 95% CI: 1.3, 5.9) and skills (mean difference, 3.3; 95% CI: 0.9, 5.7; n = 62) compared to those without RAP-eL (n = 36). Rheumatoid Arthritis for Physiotherapists e-Learning remains embedded in the curriculum. Conclusion This study demonstrated both readiness and success of the sustainable implementation of RAP-eL within a prelicensure physical therapy curriculum. J Orthop Sports Phys Ther 2017;47(9):652-663. doi:10.2519/jospt.2017.7281.
29557725 Lifetime exposure to self-reported occupational noise and prevalent rheumatoid arthritis i 2017 Jul Multiple risk factors for rheumatoid arthritis (RA) have been studied, but there is a dearth of research on occupational noise, which is highly prevalent in the United States (U.S.). This study aimed to determine whether occupational noise exposure was associated with an elevated risk of prevalent RA in the U.S. general population. Data from the 2011 to 2012 cross-sectional, population-based National Health and Nutrition Examination Survey were used for secondary analysis. Self-reported lifetime exposure to very loud noise was linked to self-reported doctor-diagnosed RA in a sample of 4192 participants. Weighted logistic regression was used to obtain nationally representative prevalence odds ratios (OR). The main and fully adjusted models yielded OR = 3.98 (95% CI: 1.74, 9.11) and OR = 2.84 (95% CI: 1.23, 6.57) for participants exposed for ≥ 15 years compared to never exposed participants. Excluding those diagnosed with RA more than five years before the interview, the effect dropped to OR = 3.67 (95% CI: 1.06, 12.75) in the main model, and was no longer significant in the fully adjusted model (OR = 2.68, 95% CI: 0.80, 8.96). The only significant effect modifier was race/ethnicity, with higher risk in Non-Hispanic whites. To conclude, long-term occupational noise exposure might be a modifiable risk factor for RA, but currently, the evidence base is very thin and tenuous.
28358698 Increased Numbers of CD4(+)CD25(+) and CD8(+)CD25(+) T-Cells in Peripheral Blood of Patien 2017 Mar AIM: To investigate T-cell subpopulations in peripheral blood of human parvovirus B19 DNA-positive (B19(+)) and -negative (B19(-)) patients with rheumatoid arthritis (RA) and healthy persons. PATIENTS AND METHODS: Blood samples were collected from 115 patients with RA and 47 healthy volunteers; 27 patients with RA and nine controls were B19(+) Cluster of differentiation (CD) 4, 8, 25 and 45RA were analyzed on blood cells. CD25 expression on CD4(+)CD45RA(+), CD4(+)CD45RA(-), CD8(+)CD45RA(+), CD8(+)CD45RA(-) subsets were analyzed by flow cytometry. RESULTS: The percentage of CD25(low) and CD25(hi) cells was increased on CD4(+)CD45RA(+), CD4(+)CD45RA(-) T-cells and the percentage of CD25(+) cells was increased on CD8(+)CD45RA(+), CD8(+)CD45RA(-) T-cells of B19(+) patients with RA in comparison with B19(-) patients and controls. CONCLUSION: Raised levels of CD4 and CD8 regulatory T-cells in B19(+) RA patients could cause down-regulation of antiviral clearance mechanisms and lead to activation of persistent human parvovirus B19 infection in patients with RA.
28440447 Anti‑inflammatory effects of oxymatrine on rheumatoid arthritis in rats via regulating t 2017 Jun Oxymatrine (OMT), a monosomic alkaloid extracted from the Chinese herb, Sophora flavescens Ait, has long been used as a traditional Chinese medicine for the treatment of inflammatory diseases. The aim of the present study was to investigate the potential anti‑inflammatory effect of OMT, and its modulation on imbalance between regulatory T (Treg) cells and T helper (Th) 17 cells in rats with collagen‑induced arthritis (CIA). Sprague‑Dawley rats were immunized with type II collagen and following a second collagen immunization, the rats were treated with OMT or dexamethasone (DXM) intraperitoneally once a day for 43 days. Paw swelling, arthritic score and joint histopathology were evaluated. The Treg/Th17‑mediated autoreactive response was assessed by determining serum levels of inflammatory response cytokines, including tumor necrosis factor (TNF)‑α and interleukin (IL)‑17, using an enzyme‑linked immunosorbent assay. The mRNA levels of forkhead box P3 (FOXP3) and retinoic acid‑related orphan receptor (ROR)γt in spleen cells stimulated with type II collagen were determined using reverse transcription‑quantitative polymerase chain reaction analysis. In addition, the protein expression levels of FOXP3 and RORγt were measured using western blot analysis. The results showed that OMT treatment significantly reduced the severity of CIA, markedly abrogating paw swelling, arthritic scores and synovial hyperplasia, and the increased loss in body weight. OMT significantly reduced the production of TNF‑α and IL‑17A, upregulated FOXP3 and downregulated RORγt in rats with CIA. In conclusion, the present study demonstrated that OMT exhibited a protective effect on rheumatoid arthritis (RA) through the inhibition of inflammation and regulation of Treg/Th17 in the CIA rats, suggesting that OMT may be used as an immune suppressive and cartilage protective medicine in human RA.
28432580 Corneal melting in rheumatoid arthritis patients treated with a tectonic reinforcing corne 2018 Jun PURPOSE: Corneal melting with perforation is a severe ophthalmic complication of autoimmune disorders such as rheumatoid arthritis. It requires urgent medical management in order to maintain the integrity of the globe and preserve vision. Treating this complication by penetrating keratoplasty is problematic due to the high rate of recurrence of corneal melting as well as other complications. We describe the use of a tectonic fresh-tissue corneolimbal covering graft. METHODS: An interventional case series including three patients that presented to our tertiary center between 2000 and 2015 with corneal melting and perforation, secondary to rheumatoid arthritis. Emergency surgery included suturing of a 13.00- to 13.50-mm full-thickness fresh-tissue corneolimbal covering graft to the patient's posterior limbal zone. RESULTS: The corneolimbal graft maintained the integrity of the cornea in all cases, by sealing the perforation and promoting the creation of a fibrovascular scar at the area of corneal melting. There were no complications, recurrences of host corneal melting, or perforation during the follow-up period. CONCLUSION: Fresh-tissue full-thickness corneolimbal grafts may be used to cover emergency corneal melting and perforations secondary to rheumatoid arthritis.
28730751 Tuberculosis and biologics in rheumatology: A special situation. 2017 Oct India has a huge patient burden of rheumatic diseases (RDs) including rheumatoid arthritis. The use of biologics has transformed the treatment paradigm for RD; however, biologic treatment-related infections (especially tuberculosis [TB]) are an area of potential concern for TB-endemic nations like India. Anti-tumor necrosis factor (TNF) therapy impairs the physiological TNF-mediated signaling and may cause reactivation and dissemination of latent TB infection (LTBI). Careful screening is, thus, crucial in RD patients who are about to commence anti-TNF treatment. To date, there is no consensus available for the screening, evaluation and treatment of LTBI as well as on the drug dosage and duration regimen (monotherapy or combination therapy) in the Indian population. An evidence-based algorithm for LTBI screening and management in RD patients undergoing biologic disease-modifying anti-rheumatic drug therapy is suggested in this review for Indian rheumatologists. The proposed algorithm guides physicians through a step-wise screening approach, including medical history, tuberculin skin test, interferon gamma release assay, chest radiograph and management of LTBI with isoniazid therapy or its combination with rifampicin. Further, the provided algorithm can aid the national bodies (such as National TB Control Program) in formulating recommendations for LTBI in this high-risk population.
28043998 Presence of anticitrullinated protein antibodies in a large population-based cohort from t 2017 Jul OBJECTIVES: To determine the prevalence of anticitrullinated protein antibodies (ACPAs) and their association with known rheumatoid arthritis (RA) risk factors in the general population. METHODS: Lifelines is a multidisciplinary prospective population-based cohort study in the Netherlands. Cross-sectional data from 40 136 participants were used. The detection of ACPA was performed by measuring anti-CCP2 on the Phadia-250 analyser with levels ≥6.2 U/mL considered positive. An extensive questionnaire was taken on demographic and clinical information, including smoking, periodontal health and early symptoms of musculoskeletal disorders. RA was defined by a combination of self-reported RA, medication use for the indication of rheumatism and visiting a medical specialist within the last year. RESULTS: Of the total 40 136 unselected individuals, 401 (1.0%) had ACPA level ≥6.2 U/mL. ACPA positivity was significantly associated with older age, female gender, smoking, joint complaints, RA and first degree relatives with rheumatism. Of the ACPA-positive participants, 22.4% had RA (15.2% had defined RA according to our criteria and 7.2% self-reported RA only). In participants without RA, 311 (0.8%) were ACPA-positive. In the non-RA group, older age, smoking and joint complaints remained significantly more frequently present in ACPA-positive compared with ACPA-negative participants. CONCLUSIONS: In this large population-based study, the prevalence of ACPA levels ≥6.2 U/mL was 1.0% for the total group and 0.8% when excluding patients with RA. Older age, smoking and joint complaints were more frequently present in ACPA-positive Lifelines participants. To our knowledge, this study is the largest study to date on ACPA positivity in the general, mostly Caucasian population.
27886691 Pharmacotherapy Pearls for the Geriatrician: Focus on Oral Disease-Modifying Antirheumatic 2017 Feb Providing safe and effective pharmacotherapy to the geriatric patients with rheumatological disorders is an ongoing struggle for the rheumatologist and geriatrician alike. Cohesive communication and partnership can improve the care of these patients and subvert adverse outcomes. Disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, and the newest oral agent for treatment of rheumatoid arthritis, tofacitinib, have distinctive monitoring and adverse effect profiles. This article provides the general practitioner or geriatrician with clinically relevant pearls regarding the use of these interventions in older patients.
28043761 The effect of body mass index on clinical response to abatacept as a first-line biologic f 2017 Oct OBJECTIVE: To assess the impact of baseline body mass index (BMI) on the efficacy and retention of intravenous abatacept at 6 months in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: This was a 6-month analysis of a 2-year, non-interventional, international, prospective study. Baseline characteristics, clinical response and retention rates were compared by BMI subgroup: underweight/normal, overweight and obese (<25, 25 to <30 and ≥30kg/m(2), respectively). RESULTS: BMI was reported in 643/672 (96%) patients: 264 (41%) were underweight/normal, 224 (35%) overweight and 155 (24%) obese. At baseline, the obese group had more active disease (mean [95% confidence intervals] 28-joint Disease Activity Score [C-reactive protein; derived] 4.6 [4.5, 4.7], 4.8 [4.7, 5.0] and 5.1 [4.9, 5.2] for underweight/normal, overweight and obese groups, respectively), a higher prevalence of metabolic disorders, a greater proportion of women and a lower proportion of patients with rheumatoid factor positivity. There were no significant differences in the percentages of patients achieving a good/moderate European League Against Rheumatism response by BMI group (80.7, 86.1 and 77.0% for underweight/normal, overweight and obese groups, respectively; P=0.178). Overall retention rates at 6 months did not differ across groups (89, 92 and 89% for underweight/normal, overweight and obese groups, respectively; log-rank P=0.382). After adjustment for baseline characteristics, BMI was not significantly associated with risk of discontinuation (reference BMI<25kg/m(2); hazard ratio [95% confidence intervals] 0.46 [0.22, 0.99] and 0.69 [0.34, 1.41] for overweight and obese patients, respectively). CONCLUSION: BMI does not impact abatacept clinical response or retention in biologic-naïve patients with RA.
28094760 Treat-to-target biologic therapy in patients with rheumatoid arthritis is more efficacious 2017 Mar OBJECTIVES: Rheumatoid arthritis (RA) is a chronic, devastating disease. Treat-to-target strategy (T2T) more than the usual care, reduces disease activity by using aggressively all therapeutic options. The aim of the study was to evaluate our hypothesis that T2T strategy using biologic disease-modifying anti-rheumatic drugs (bDMARDs), when needed, is also safer than the usual care characterised by delayed initiation of bDMARDs. METHODS: Disease activity was regularly measured by DAS-28 until the end of treatment with the first bDMARD. All adverse events (AEs) and their severity were recorded. Cox proportional-hazards models were performed examining the association of treatment groups, with the risk of first AE. RESULTS: There were 113 patients in T2T and 250 patients in usual care group. The likelihood (adjusted hazard ratio, HR) of achieving remission or LDA was 71% higher in the T2T group than in the usual care group, as it has been already shown by others. The novel finding of our work was that AEs, including cancers, were less frequent in the T2T group with the corresponding HRs being less than 0.50 for serious AEs, infections and serious infections (significant or marginally non-significant results). There were 15 new cancer cases in usual care and 1 in T2T group (IR 1.99 vs. 0.4, p=0.027). CONCLUSIONS: Treat-to-target treatment with bDMARDs offers a safer, rapid and better long-term outcome to patients with RA.
27766911 The minimally important difference for the Japanese version of the health assessment quest 2017 May OBJECTIVE: To validate the minimally important difference (MID) of physical function using the Japanese version of the Health Assessment Questionnaire (J-HAQ) in a cohort of rheumatoid arthritis (RA). METHODS: Patients who participated in a cohort study in both October 2008 and April 2009 were analyzed. Patients self-rated their change in overall status over 6 months using a 5-point Likert scale ("much better", "somewhat better", "same", "somewhat worse", or "much worse"). The MID for J-HAQ score was defined as the mean J-HAQ score change in patients who rated themselves "somewhat better". An effect size (ES) of 0.2-0.5 was considered to be suitable for MID. RESULTS: A total of 4560 patients were analyzed. The mean (standard deviation [SD]) MID for J-HAQ score was -0.06 (0.29), corresponding to an ES of 0.08. As exploratory analysis, 1999 patients with a J-HAQ score ≥0.5 and 28-joint disease activity score (DAS28) ≥ 2.6 at baseline were assessed. The mean (SD) MID for J-HAQ score of these patients was 0.13 (0.01), corresponding to an ES of 0.21. CONCLUSIONS: The MID for J-HAQ score was 0.13 in patients with baseline J-HAQ score ≥0.5 and DAS28 ≥ 2.6. The MID for J-HAQ score was influenced by disease status and functional disability.
24702788 Diminished soluble levels of growth arrest specific protein 6 and tyrosine kinase receptor 2017 Jan AIM: Growth arrest specific protein 6 (Gas-6) and its tyrosine kinase receptor Axl plays an important role in apoptosis, and regulation of innate immune response, therefore, we investigated their plasma concentrations in Rheumatoid arthritis (RA) patients and correlated them to clinical, laboratory and radiological parameters of the disease. METHODS: Plasma from 77 RA patients and 50 normal healthy subjects were assayed for plasma Gas6 and Axl levels. Demographic, clinical and serological data were prospectively assessed. Rheumatoid arthritis disease activity was assessed using 28-joint Disease Activity Score (DAS-28) and functional capacity by modified health assessment questionnaire (mHAQ). Standardized x-rays for hands and feet were done to all participants. RESULTS: The level of Gas6 and Axl were significantly decreased in the RA patients compared to those of the healthy control subjects. Levels of Gas6 correlated positively with Axl levels in both patients and healthy control. Gas6 levels were remarkably reduced in those patients with erosive RA than those without. Levels of Gas6 were found to be negatively correlated with the presence of erosive disease and positively correlated with DAS-28, ESR, Leucocytosis and IL6. CONCLUSION: The plasma concentrations of Gas6 and Axl are altered in RA patients and thus may have a role in RA pathogenesis. Further mechanistic studies on the involvement of all TAM receptors tyrosine kinases pathway in RA are needed to help in understanding the pathogenesis and possibly aid in diagnosis and future treatments of RA especially for patients with erosive disease.
27856318 Sympathetic nerve repulsion inhibited by designer molecules in vitro and role in experimen 2017 Jan 1 AIMS: In rheumatoid arthritis and collagen type II arthritis (CIA), sympathetic nerve fibers get lost in inflamed tissue. The process is probably induced by nerve repellent factors like semaphorin 3F (SEMA3F). Repulsion of sympathetic nerve fibers in inflamed tissue has proinflammatory effects due to the loss of anti-inflammatory neurotransmitters. We hypothesized that design molecules like antibodies and specific peptides that inhibit nerve fiber repulsion can ameliorate CIA. MATERIALS AND METHODS: Two blocking antibodies were used and four blocking peptides were generated using the phage display technique with the targets of SEMA3F and plexin-A2. All blocking molecules were tested in vitro using a sympathetic neurite outgrowth assay. CIA was induced by collagen type II in mice. KEY FINDINGS: In the neurite outgrowth assay, the two antibodies against plexin-A2 and neuropilin-2 as well as the four blocking peptides - two SEMA3F analogous peptides (WLFQRDPGDR, QATVKWLFQRDPGDRR) and two plexin A2 analogous peptides (DSSDQFSFDYELEQN, DSSIQFFSFEKDKERI) - were able to block sympathetic nerve fiber repulsion in vitro (at 150-600nmol/l). Administration of the two antibodies prophylactically on day 4 after immunization did not change clinical CIA. Similarly, using the top candidate antibody to plexin-A2 after CIA onset (mild score of 4 points, maximum=52 points), did not ameliorate CIA. The tested blocking peptides were not recovered in peripheral blood after i.v. and i.p. administration. SIGNIFICANCE: While designer molecules blocked nerve fiber repulsion in vitro, therapeutic administration in vivo did not change CIA. Possible strategies to overcome negative effects demonstrated in vivo are discussed.
28071693 IK acts as an immunoregulator of inflammatory arthritis by suppressing T(H)17 cell differe 2017 Jan 10 Pathogenic T helper cells (T(H)) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of T(H)1 and T(H)17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and T(H)17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.