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ID PMID Title PublicationDate abstract
28821984 Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian T 2018 Feb The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.
29448870 A new assessment tool for ulnar drift in patients with rheumatoid arthritis using pathophy 2019 Jan OBJECTIVES: To establish a new assessment tool for ulnar drift (UD) in rheumatoid arthritis (RA). METHODS: We established an observational cohort of 67 patients (134 rheumatoid hands) beginning in 2004. Fifty-two patients (100 hands) had follow-up in 2009 and 37 patients (63 hands) completed follow-up in 2015. UD was evaluated with the Fearnley classification and our scoring method, which assesses four parameters of the metacarpophalangeal joint. Cluster analysis using UD parameters divided hands into groups. Changes in UD over time, correlation of the Fearnley stage and cluster with a functional assessment, and reliability of the parameters were analyzed. RESULTS: UD increased and worsened over time according to the trend test. A dendrogram indicated five clusters would be appropriate. Both the Fearnley classification and cluster were associated with function; however, our method related to function more linearly (R-squared: 0.42). We found one type of hand in which bone destruction precedes the joint dislocation and one type in which joint dislocation progresses with little deviation during UD progression. CONCLUSION: Our UD evaluation appeared to be simple and related to function. Additionally, it enables dividing UD hands into five stages. Thus, our assessment should be beneficial compared to the Fearnley classification in considering treatments of UD.
29573850 Clinical presentation of immune checkpoint inhibitor-induced inflammatory arthritis differ 2018 Dec INTRODUCTION: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy, increasingly utilized to treat malignancies. Inflammatory arthritis (IA) is a potential consequence of ICI use, but there is limited information to guide evaluation and management of this immune-related adverse event (irAE). This study aimed to characterize clinical phenotypes, IA treatment and response in the largest cohort of patients with ICI-induced IA reported to date. METHODS: Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of autoimmune disease were included. Data were analyzed by ICI treatment regimen; treatments included combination CTLA-4/PD-1 inhibition, anti-PD-1 or anti-PD-L1 monotherapy. Relationship to the development of other irAEs, management of IA, and outcomes of IA management were evaluated. RESULTS: Of 30 patients identified, those treated with combination ICI therapy were more likely to present with knee arthritis, to have higher levels of C-reactive protein, to have already had another irAE, and to have a reactive arthritis-like phenotype. In contrast, patients treated with ICI monotherapy were more likely to have initial small joint involvement and to have IA as their only irAE. Ten patients required additional immunosuppression beyond corticosteroids, with TNF-inhibitors and/or methotrexate. Tumor progression while on non-corticosteroid immunosuppression was not seen in those with initial tumor response to ICIs. CONCLUSION: These data suggest that distinct IA phenotypes may emerge with exposure to different ICI regimens. The majority of patients referred to rheumatology required systemic immunosuppression to manage their IA symptoms. Tumor progression was not seen in patients requiring TNF-inhibitors.
29929518 Obliterative bronchiolitis associated with rheumatoid arthritis: analysis of a single-cent 2018 Jun 22 BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune condition characterized by erosive inflammation of the joints. One rare pulmonary manifestation is obliterative bronchiolitis (OB), a small airways disease characterized by the destruction of bronchiolar epithelium and airflow obstruction. METHODS: We retrospectively reviewed the clinical data of patients with rheumatoid arthritis-associated obliterative bronchiolitis (RA-OB) from 01/01/2000 to 12/31/2015. Presenting clinical features, longitudinal pulmonary function testing, radiologic findings, and independent predictors of all-cause mortality were assessed. RESULTS: Forty one patients fulfilled criteria for diagnosis of RA-OB. There was notable female predominance (92.7%) with a mean age of 57 ± 15 years. Dyspnea was the most common presenting clinical symptom. Median FEV1 was 40% (IQR 31-52.5) at presentation, with a mean decline of - 1.5% over a follow-up period of thirty-three months. Associated radiologic findings included mosaic attenuation and pulmonary nodules. A majority of patients (78%) received directed therapy including long-acting inhalers, systemic corticosteroids or other immunosuppressive agents, and macrolide antibiotics. All-cause mortality was 27% over a median follow-up of sixty-two months (IQR 32-113). No distinguishable predictors of survival at presentation were found. CONCLUSIONS: RA-OB appears to have a stable clinical course in the majority of patients despite persistent symptoms and severe obstruction based on presenting FEV1.
29128828 Quantitative assessment of betamethasone dual-acting formulation in urine of patients with 2018 Feb 5 Quantitative evaluation and assessment of pharmacokinetic parameters of Diprospan(®) (suspension for injection 7mg/mL (2mg+5mg/mL) of betamethasone) were performed in urine samples taken from patients with rheumatoid arthritis or ankylosing spondylitis for 28days after systemic intramuscular administration in routine clinical practice in an open-comparative prospective cohort study. The maximum betamethasone concentration was reached at day 4 of the follow-up; in some cases, β-phase of elimination of the drug was appeared at day 14 or at day 21 of the follow-up. The deferred β-phase elimination was likely a consequence of the physiological characteristics of the patients or of the influence of non-steroidal agents. The half-life of betamethasone was 8.5days. The elimination rate constant was 2.49h-1; the mean clearance was 4.72L/d. The recommended frequency of the drug administration to its complete elimination was estimated up to 48days. Mann-Whitney test showed no significant differences in pharmacokinetic characteristics between male and female subjects. The prolonged elimination phase was observed in patients with deviations in their body mass index, continual treatment by diclofenac and nimesulide or, possibly, after consuming an alcohol. The study was recorded in Clinical Trials open source with identifier NCT03119454.
29469766 Herpes zoster as a cause of atypical chronic ulcerations associated with tofacitinib. 2018 Jan 15 Tofacitinib is a targeted inhibitor of janus kinase (JAK), currently approved for the treatment of rheumatoid arthritis. We present a patient on treatment withtofacitinib who had an episode of classic dermatomal herpes zoster followed months later by atypical chronic cutaneous ulcers also caused by herpes zoster.
29790395 Hyaluronic acid-conjugated pH-sensitive liposomes for targeted delivery of prednisolone on 2018 May AIM: The treatment of rheumatoid arthritis remains a challenge as available therapies still entail the risk of deleterious off-target effects. The present study describes hyaluronic acid-conjugated pH-sensitive liposomes as an effective drug delivery-targeting strategy to synovial cells. MATERIALS & METHODS: Therapeutic, cytotoxic and targeting potential of developed liposomes were studied in vitro using macrophages and fibroblasts cell lines. RESULTS & CONCLUSION: Results suggest an enhanced cellular uptake of conjugated liposomes, mainly mediated by caveolae- and clathrin-dependent endocytosis. In vitro release studies demonstrated that prednisolone was preferentially released under acidic conditions mimicking intracellular endosomal compartments. Overall, results revealed that conjugated pH-sensitive liposomes are a promising nanoapproach for the targeted delivery of prednisolone within inflamed synovial cells for rheumatoid arthritis treatment.
29786138 Association of different immunosuppressive medications with periodontal condition in patie 2018 Nov BACKGROUND: The aim of this cross-sectional study was to investigate clinical periodontal findings as well as prevalence of selected potentially periodontal pathogenic bacteria in patients with rheumatoid arthritis (RA) treated with different immunosuppressive rheumatic medications. METHODS: One hundred sixty-eight patients with RA undergoing different immunosuppressive medications were included and divided into subgroups according to their medication, which was taken in the past 6 months, in detail, 1) non-steroidal anti-inflammatory drugs (NSAID) and glucocorticoids combined, and the following different disease modifying anti-rheumatic drugs (DMARDs): 2) methotrexate (MTX), 3) leflunomide, 4) MTX and TNF-α antagonists combined, 5) interleukin-6 (IL-6) antagonist, 6) MTX and rituximab combined, and 7) combination therapies of > 2 of these DMARDs. Periodontal examination consisted of papilla bleeding index (PBI), periodontal status with periodontal probing depth (PD), bleeding on probing (BOP), and clinical attachment loss (AL). Periodontitis was classified as none/mild, moderate, or severe. Samples obtained from gingival crevicular fluid were analyzed for presence of 11 periodontal pathogenic bacteria. RESULTS: Patients with MTX + TNF-α antagonists therapy showed higher PBI and BOP values compared with leflunomide (P < 0.01) and higher BOP than MTX + rituximab (P = 0.02). Porphyromonas gingivalis (P < 0.01), Treponema denticola (P < 0.01), Fusobacterium nodatum (P = 0.02) and Capnocytophaga species (P = 0.05) was associated with medication subgroup, whereby post hoc testing confirmed singular differences for several medication subgroups. CONCLUSIONS: RA medication is associated with periodontal inflammation, without differences in periodontal disease severity. Thereby, combination of MTX + TNF-α shows an increased potential to periodontal inflammation. Additionally, several differences in prevalence of selected bacteria were detected.
29043892 Tofacitinib in the treatment of active rheumatoid arthritis in adults. 2018 Jan Tofacitinib, a pan Janus kinase inhibitor, has been investigated as monotherapy in patients naive to methotrexate and in methotrexate incomplete responders and in combination with disease-modifying antirheumatic drugs in antirheumatic drug incomplete responders and TNF inhibitor failures in the Phase II and III programs. The clinical trial program demonstrated efficacy and a reasonable safety profile in these disease populations that has led to the approval of tofacitinib 5 mg twice daily orally in many countries. The pharmacology, chemistry, pharmacokinetics, pharmacodynamics, efficacy and safety in the Phase II and III clinical trials, safety in the long-term extension studies and postmarketing safety reports are the focus of this review.
29476350 Genetic polymorphism of rs9277535 in HLA-DP associated with rheumatoid arthritis and anti- 2018 Jul HLA-II molecules are critical in triggering human immune response, especially in activating CD4+ T cells. HLA-DP, belonging to HLA-II molecules, draws increasing attention for its role in presentation of viral antigen and autoantigen to T cells. Researches reported single nucleotide polymorphism (SNP) of HLA-DP associated with HBV infection and autoimmune diseases such as SLE. However, little is known about the relationship between HLA-DP and rheumatoid arthritis (RA). Rs9277535 is located in 3' UTR region of HLA-DPB1, a subunit of HLA-DP, and was reported to affect HLA-DP mRNA expression. In the present study, we explored the relationship between gene polymorphism of rs9277535 in HLA-DPB1 and RA susceptibility and progression. Samples from 254 patients with RA and 391 age- and sex-matched healthy controls were collected and genotyped by a polymerase chain reaction-high-resolution melting (PCR-HRM) assay. Serological tests (anti-CCP, rheumatoid factor, C-reactive protein, anti-keratin antibody) were detected by laboratory assays. Strong association was observed between SNP rs9277535 in HLA-DP and RA susceptibility (allele frequency distribution: OR = 1.409, 95%CI = 1.121-1.773, P = 0.004). Further validation was provided by disease model analysis (recessive model: OR = 1.889, 95%CI = 1.194-2.990, P = 0.008; dominant model: OR = 1.464, 95%CI = 1.050-2.041, P = 0.025; additive model: OR = 2.208, 95%CI = 1.335-3.652, P = 0.003). Allele A was correlated to increased risk of RA. Serological test results demonstrated patients carrying allele A of rs9277535 had elevated serum anti-CCP antibody level. The present study provided evidence that HLA-DP gene polymorphism associated with RA susceptibility. Allele A of rs9277535 in HLA-DP correlated to increased risk of RA and elevated serum anti-CCP level.
29764238 Successful administration of BI 695501, an adalimumab biosimilar, using an autoinjector (A 2018 Jun BACKGROUND: This study examined the patient handling experience and self-injection success of patients with rheumatoid arthritis (RA) administering BI 695501 using an AI. METHODS: This Phase II, 7-week, open-label, interventional study (NCT02636907) included adult patients with moderately to severely active RA not adequately controlled by DMARDs, with no experience of self-injecting with AI/pen. Patients self-injected BI 695501 via AI every 2 weeks in the AI Assessment Period (AAP). Training was given on first injection; AI handling events were recorded. Percentage of self-injection success was the primary end point. Patients could enter a 42-week pre-filled syringe (PFS) safety extension. RESULTS: The AAP was completed by 73/77 patients. In total, 216/218 (99.1%) self-injections on Days 15, 29, and 43, were successful. Nine (11.7%) patients had drug-related adverse events (AEs). Two patients reported four serious AEs (SAEs), none drug-related. Overall (in the AAP and PFS extension), 28 (36.4%) patients had drug-related AEs; nine patients had SAEs, one was considered drug-related. Five (6.5%) patients reported injection-site reactions in the AAP; 13 (18.1%) in the PFS extension. CONCLUSIONS: After training, almost all patients were successfully able to self-administer BI 695501 using an AI. BI 695501 via AI (and via PFS in the extension) was well tolerated. CLINICAL TRIAL REGISTRATION: NCT02636907.
28285975 Monounsaturated fatty acids might be key factors in the Mediterranean diet that suppress r 2018 Apr BACKGROUND & AIMS: The Mediterranean diet is reportedly effective in suppressing disease activity in rheumatoid arthritis (RA), but the key elements responsible for this effect remain unknown. The presented study therefore aimed to identify such elements. METHODS: This study included 208 consecutive patients with RA (RA group) and 205 age- and sex-matched healthy volunteers (controls) from the prospective "TOMORROW" cohort study that has been ongoing since 2010 were included in this study. Food and nutrient intake was assessed using the brief self-administered diet history questionnaire (BDHQ), Mediterranean diet scores were calculated based on intake by controls and disease activity was determined from disease activity scores in 28 joints and erythrocyte sedimentation rates (DAS28-ESR). RESULTS: Intake of monounsaturated fatty acids (MUFA) was significantly lower in the RA, than in the control group (P = 0.003) and the ratio of consumed monounsaturated to saturated fatty acid (MUFA/SFA) significantly differed within the RA group after being sub-classified according to DAS28-ESR. Moreover, DAS28-ESR significantly correlated with MUFA/SFA intake after age adjustment (R = -0.228, P < 0.01). Logistic regression analysis selected high MUFA intake as an independent predictor of remission in the RA group with borderline boundary significance (odds ratio, 1.97; 95% CI, 0.98-3.98; P = 0.057). Changes in DAS28-ESR between 2010 and 2011 significantly correlated with MUFA/SFA intake after age adjustment (R = 0.180, P = 0.01). CONCLUSIONS: Daily MUFA intake, a component of the Mediterranean diet score, might suppress disease activity in RA patients.
30040287 [A man with rheumatoid arthritis and a painful neck]. 2018 Jun 22 An 80-year-old man with long-standing rheumatoid arthritis presented with severe neck pain. No preceding trauma had occurred and he had no neurological complaints. A CT scan revealed vertical atlanto-axial subluxation without compression of the medulla oblongata. After conservative treatment the pain diminished. There were no neurological complications at follow-up.
30111357 A comparative clinical study of PF-06410293, a candidate adalimumab biosimilar, and adalim 2018 Aug 15 BACKGROUND: This double-blind, randomized, 78-week study evaluated the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of PF-06410293, a candidate adalimumab biosimilar, versus adalimumab reference product (Humira(®)) sourced from the EU (adalimumab-EU) in biologic-naïve patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) (10-25 mg/week). We report results for the first 26 weeks of treatment. METHODS: Patients with active RA (N = 597) were randomly assigned (1:1) to PF-06410293 or adalimumab-EU, while continuing with MTX treatment. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at week 12. Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the ACR20 difference between the two arms was entirely contained within the symmetric equivalence margin (±14%). Additionally, a two-sided 90% CI was calculated by using an asymmetric equivalence margin (-12%, 15%). Secondary efficacy endpoints to week 26 included ACR20/50/70, change from baseline Disease Activity Score based on high-sensitivity C-reactive protein [DAS28-4(CRP)], European League Against Rheumatism (EULAR) response, DAS28-4(CRP) of less than 2.6, and ACR/EULAR remission. QuantiFERON-TB testing was performed at screening and week 26. RESULTS: Patients (78.7% of whom were female and whose mean age was 52.5 years) had a mean baseline RA duration of 6.8 years. The mean baseline DAS28-4(CRP) values were 5.9 (PF-06410293) and 6.1 (adalimumab-EU). The observed week-12 ACR20 values were 68.7% (PF-06410293) and 72.7% (adalimumab-EU) in the intention-to-treat population. With non-responder imputation, the treatment difference in week-12 ACR20 was -2.98% and corresponding CIs-95% CI (-10.38%, 4.44%) and 90% CI (-9.25%, 3.28%)-were entirely contained within the equivalence margins (symmetric and asymmetric, respectively). The secondary efficacy endpoints were similar between arms. Over 26 weeks, injection-site reactions occurred in 1.7% versus 2.0%, hypersensitivity events in 4.4% versus 8.4%, pneumonia in 0.7% versus 2.0%, and opportunistic infections in 2.4% versus 1.7% in the PF-06410293 and adalimumab-EU arms, respectively. One death due to myocardial infarction occurred (adalimumab-EU arm). Rates of anti-drug antibody incidence were 44.4% (PF-06410293) and 50.5% (adalimumab-EU). CONCLUSIONS: The study results demonstrate that efficacy, safety, and immunogenicity of PF-06410293 and adalimumab-EU were similar during the first 26 weeks of treatment in patients with active RA on background MTX. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02480153 . First posted on June 24, 2015; EU Clinical Trials Register EudraCT number: 2014-000352-29 . Start date: October 27, 2014.
30562482 Role of small ubiquitin-like modifier proteins-1 (SUMO-1) in regulating migration and inva 2019 Feb 1 Rheumatoid arthritis (RA) is featured by erosive cartilage and bone destruction. The enhancing aggressive property of fibroblast-like synoviocytes (FLSs) plays a critical role in this process. Small ubiquitin-like modifier (SUMO) proteins, including SUMO-1, SUMO-2, SUMO-3 and SUMO-4, participate in regulating many cellular events such as survival, migration and signal transduction in some cell lines. However, their roles in the pathogenesis of RA are not well established. Therefore, we evaluated the role of SUMO proteins in RA FLSs migration and invasion. We found that expression of both SUMO-1 and SUMO-2 was elevated in FLSs and synovial tissues (STs) from patients with RA. SUMO-1 suppression by small interference RNA (siRNA) reduced migration and invasion as well as MMP-1 and MMP-3 expression in RA FLSs. We also demonstrated that SUMO-1 regulated lamellipodium formation during cell migration. To explore further into molecular mechanisms, we evaluated the effect of SUMO-1 knockdown on the activation of Rac1/PAK1, a critical signaling pathway that controls cell motility. Our results indicated that SUMO-1-mediated SUMOylation controlled Rac1 activation and modulated downstream PAK1 activity. Inhibition of Rac1 or PAK1 also decreased migration and invasion of RA FLSs. Our findings suggest that SUMO-1 suppression could be protective against joint destruction in RA by inhibiting aggressive behavior of RA FLSs.
30620289 Rituximab induces a lasting, non-cumulative remodelling of the B-cell compartment. 2019 Jul OBJECTIVES: Reconstitution of B-cells after their therapeutic depletion with rituximab mimics the ontogeny of the B-cell linage in patients with rheumatoid arthritis. However, little is known about the effects of multiple cycles of treatment on the repletion kinetics and their long-lasting effects on the B-cell compartment. We therefore compared the recovery capacity of the B cell subpopulations between patients who experienced their first cycle of rituximab and those who experienced successive cycles. METHODS: The distribution of the different B-cell subsets was characterised by multiparametric flow cytometry in the peripheral blood of 29 patients in the first rituximab course (naïve cycles) and 40 patients in successive cycles. Samples were obtained at baseline and at 3, 6, and 8 months of each cycle. RESULTS: The baseline percentage of B-cell subsets was similar among successive cycles. Therefore, successive cycles were grouped for comparison with naïve cycles. Patients in naïve cycles had higher percentages at baseline of both total and memory B-cells. However, the recovery of the different B-cell subsets was similar between naïve and successive cycles. In naïve patients the percentage of transitional B-cells significantly correlated with disease activity at baseline. CONCLUSIONS: Rituximab induces a long-term reshape of the B-cell compartment while multiple cycles of rituximab do not induce cumulative effects on B-cell subpopulations. Transitional B-cells seem to be associated with higher disease activity, although further studies are needed to determine if they can be used as a biomarker to predict the need for rituximab retreatment.
28480581 Automatic quantification of bone marrow edema on MRI of the wrist in patients with early a 2018 Feb PURPOSE: To investigate the feasibility of automatic quantification of bone marrow edema (BME) on MRI of the wrist in patients with early arthritis. METHODS: For 485 early arthritis patients (clinically confirmed arthritis of one or more joints, symptoms for less than 2 years), MR scans of the wrist were processed in three automatic stages. First, super-resolution reconstruction was applied to fuse coronal and axial scans into a single high-resolution 3D image. Next, the carpal bones were located and delineated using atlas-based segmentation. Finally, the extent of BME within each bone was quantified by identifying image intensity values characteristic of BME by fuzzy clustering and measuring the fraction of voxels with these characteristic intensities within each bone. Correlation with visual BME scores was assessed through Pearson correlation coefficient. RESULTS: Pearson correlation between quantitative and visual BME scores across 485 patients was r=0.83, P<0.001. CONCLUSIONS: Quantitative measurement of BME on MRI of the wrist has the potential to provide a feasible alternative to visual scoring. Complete automation requires automatic detection and compensation of acquisition artifacts. Magn Reson Med 79:1127-1134, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
30420245 Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoi 2019 Jun OBJECTIVES: To evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients. METHODS: The study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n = 240) or infliximab (n = 126), 92.4% of them anti-TNF naive (n = 328/355) and 96.6% of them co-treated with methotrexate (n = 341/353) with up to 18 months follow-up. ADA positivity was measured by enzyme-linked immunosorbent assay. The cumulative incidence of ADA was estimated, and potential bio-clinical factors were investigated using a Cox regression model on interval-censored data. RESULTS: ADAs were detected within 18 months in 19.2% (n = 46) of the adalimumab-treated patients and 29.4% (n = 37) of the infliximab-treated patients. The cumulative incidence of ADA increased over time. In the adalimumab and infliximab groups, respectively, the incidence was 15.4% (5.2-20.2) and 0% (0-5.9) at 3 months, 17.6% (11.4-26.4) and 0% (0-25.9) at 6 months, 17.7% (12.6-37.5) and 34.1% (11.4-46.3) at 12 months, 50.0% (25.9-87.5) and 37.5% (25.9-77.4) at 15 months and 50.0% (25.9-87.5) and 66.7% (37.7-100) at 18 months. Factors associated with a higher risk of ADA development were: longer disease duration (1-3 vs. < 1 year; adalimumab: HR 3.0, 95% CI 1.0-8.7; infliximab: HR 2.7, 95% CI 1.1-6.8), moderate disease activity (DAS28 3.2-5.1 vs. < 3.2; adalimumab: HR 6.6, 95% CI 1.3-33.7) and lifetime smoking (infliximab: HR 2.7, 95% CI 1.2-6.3). CONCLUSIONS: The current study focusing on patients co-treated with methotrexate for more than 95% of them found a late occurrence of ADAs not previously observed, whereby the risk continued to increase over 18 months. Disease duration, DAS28 and lifetime smoking are clinical predictors of ADA development.
29377768 Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human 2018 Feb Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.
30564242 Roles of Myeloid-Derived Suppressor Cell Subpopulations in Autoimmune Arthritis. 2018 Emerging evidence suggests the promise of the use of myeloid-derived suppressor cells (MDSCs) in inflammatory disorders based on their unique immune-intervention properties. However, the roles of MDSCs in autoimmune arthritis are not completely understood. Indeed, their immunosuppressive functions in arthritic conditions remain controversial, with heterogeneity among MDSCs and differential effects among subpopulations receiving much attention. As a result, it is necessary to determine the roles of MDSC subpopulations in autoimmune arthritis to clarify their diagnostic and therapeutic potential. Interestingly, in the inflammation niche of autoimmune arthritis, each MDSC subpopulation can exhibit both alternatives of a given characteristic. Moreover, polymorphonuclear MDSCs (PMN-MDSCs) are likely to be more suppressive and stable compared with monocytic MDSCs (MO-MDSCs). Although various important cytokines associated with the differentiation of MDSCs or MDSC subpopulations from immature myeloid precursors, such as granulocyte colony-stimulating factor (G-CSF), have been largely applied in external inductive systems, their roles are not entirely clear. Moreover, MDSC-based clinical treatments in rheumatoid arthritis (RA) continue to represent a significant challenge, as also reported for other autoimmune diseases. In this review, we describe the effects and actions of MDSC subpopulations on the development of autoimmune arthritis and analyze several types of MDSC-based therapeutic strategies to provide comprehensive information regarding immune networks and a foundation for more effective protocols for autoimmune arthritis.