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ID PMID Title PublicationDate abstract
28755075 Rheumatoid arthritis-associated spinal neuroarthropathy with double-level isthmic spondylo 2019 Sep INTRODUCTION: To the best of our knowledge, there has been no report regarding rheumatoid arthritis associated with spinal neuroarthropathy and combined double-level isthmic spondylolisthesis. Here, we report a rare case of spinal neuroarthropathy with double-level isthmic spondylolisthesis in a rheumatoid arthritis (RA) patient. A 56-year-old female patient under medical treatment for RA during the last 13 years presented aggravating radiating pain to her right lower extremity and a limping gait developed 4 months ago. The disease activity of RA had remained low for a long time. Serial radiographs during last 8-year follow-up showed progressive dislocation at L4-L5 and L5-S1 with double-level isthmic spondylolisthesis and severe destructive status at the last follow-up. The patient underwent decompression and circumferential fusion with sacropelvic fixation and acceptable reduction was obtained. CONCLUSION: A RA patient with double-level isthmic spondylolisthesis showed a progressive destructive lesion. In addition to clinical presentations, the imaging findings were very similar to ones of spinal neuroarthropathy. The authors conclude that this Grand Round case probably had SNA secondary to RA and that this, combined with two-level isthmic spondylolisthesis, resulted in her rapidly progressing destructive lumbar lesion.
28555524 Ellipticine inhibits the proliferation and induces apoptosis in rheumatoid arthritis fibro 2017 Aug OBJECTIVE: Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an alkaloid isolated from Apocyanaceae plants. This study was designed to investigate the effects of ellipticine on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). METHODS: RA-FLSs were exposed to different concentrations of ellipticine (i.e., 0.5, 1, 2, 4 and 8 μM) for 24-72h and measured for viability, proliferation and apoptosis. The involvement of signal transducer and activators of transcription 3 (STAT3) signaling in the action of ellipticine was determined by Western blot analysis, luciferase reporter assay and rescue experiments. RESULTS: Ellipticine treatment significantly inhibited the viability and proliferation of RA-FLSs in a concentration-dependent manner. In contrast, ellipticine exposure did not alter the viability of normal human FLSs. Moreover, ellipticine triggered significant apoptosis and increased caspase-3 activity in RA-FLSs. Mechanistically, ellipticine reduced the phosphorylation of STAT3 and downregulated the expression of Mcl-1, cyclin D1 and Bcl-2. Luciferase reporter assay demonstrated that ellipticine treatment led to a significant inhibition of STAT3-mediated transcriptional activity in RA-FLSs. Overexpression of constitutively active STAT3 reversed the suppressive effects of ellipticine on RA-FLSs, which was accompanied by restoration of Mcl-1, cyclin D1 and Bcl-2. DISCUSSION AND CONCLUSIONS: Ellipticine shows anti-proliferative and pro-apoptotic effects on RA-FLSs through inhibition of the STAT3 pathway and may have therapeutic potential in RA.
28120731 [Serious complications during treatment with methotrexate: also in chronic low-dosage use] 2017 Methotrexate is a frequently prescribed drug and is considered to be safe at a low dosage. However, serious complications may occur during treatment. In this article we describe a 78-year-old male who used low-dose methotrexate for psoriatic arthritis. He died of multi-organ failure caused by sepsis and methotrexate intoxication as a result of deteriorating renal function. The second patient was a 56-year-old male who used low-dose methotrexate for rheumatoid arthritis. This patient developed pancytopenia and methotrexate pneumonitis during treatment with methotrexate. We recommend the frequent monitoring of blood count and renal and liver function tests to detect early deterioration. Furthermore, doctors should be aware of conditions and factors predisposing to methotrexate intoxication, such as impaired kidney function and co-medication. If methotrexate intoxication is suspected, intravenous folinic acid should be administered immediately.
28770826 The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients w 2017 Nov Immunoglobulin IgD might play an important role in autoimmune diseases, but the function of IgD has remained elusive, despite multiple attempts to define its biological function. Fibroblast-like synoviocytes (FLSs) are specialized cells of the synovium that play a key role in the pathogenesis of rheumatoid arthritis (RA). In this study we explored the possible roles of excessive IgD expression on the function of FLSs from RA patients (RA-FLSs). We showed that IgD Fc receptor (IgDR) was constitutively expressed on FLSs, and was significantly elevated in RA-FLSs compared with FLSs prepared from synovial tissues of healthy controls (HC-FLSs). Furthermore, IgDR was mainly detected on the cell surface and in the cytoplasm. We further detected the intrinsic binding affinity of IgD to IgDR on HC-FLSs with an equilibrium dissociation constant (K(D)) of 0.067 nmol/L. Incubation of RA-FLSs with IgD (1-10 μg/mL) for 48 h dose-dependently promoted the expression of IgDR, and stimulated the production of inflammatory cytokines and chemokines, such as IL-1β, IL-6, monocyte chemotactic protein (MCP)-1, TNF-α and receptor activator of nuclear factor-κB ligand (RANKL), thus potentially contributing to IgD-IgDR crosslinking. Moreover, incubation with IgD (0.1-10 μg/mL) for 48 h dose-dependently enhanced viability for both HC-FLSs and RA-FLSs. Our results demonstrate that IgDR is expressed on RA-FLSs and contributes to the activation of FLSs, and suggest that IgD-IgDR is a potential novel immunotherapeutic target for the management of RA.
28094753 Quantifying cutaneous adverse effects of systemic glucocorticoids in patients with rheumat 2017 May OBJECTIVES: EULAR guidelines state that adverse effects (AEs) of glucocorticoid (GC) therapy should be considered and discussed with the patient before treatment is initiated. However, reliable quantitative data, especially on cutaneous AEs of low-to-medium dose GCs are lacking. We performed a study assessing the occurrence of cutaneous AEs of GCs and its association with current and cumulative GC doses in patients with rheumatoid arthritis (RA). METHODS: In a cross-sectional study performed in 2 outpatient rheumatology centres, 381 RA patients were enrolled. They were classed into 4 groups, according their mean daily dose during the past 12 months: 0 mg (n=87), <5mg (n=108), 5-7.5 mg (n=130), and >7.5 mg (n=56) of prednisone equivalent. AEs of GC on the skin were assessed by physical examination using a predefined scoring system, and by patients' self-assessments. Data were analysed according GC dose categories and cumulative doses. RESULTS: Cushingoid habitus, easy bruising, skin atrophy, and impaired wound healing as reported by patients occurred significantly more frequently in those using a GC the past 12 months, compared to those not using a GC. At physicians' assessments, only Cushingoid habitus and ecchymosis were more prevalent in GC users. The prevalence of these AEs was statistically significantly positively associated with current and cumulative GC dose. There was low occurrence of abnormal stretch marks, acne, perioral dermatitis, alopecia and hirsutism, which were not correlated with GC use. CONCLUSIONS: Certain GC-associated cutaneous AEs are common in RA, but other AEs of GC occur infrequently at the low-to-medium GC doses used in RA.
28931878 A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis. 2017 Sep 20 N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect. Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip. We discover 20 sulfated and 4 acetylated N-glycans on IgGs. Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans. From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients. This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies. Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28546562 The interplay between host immune cells and gut microbiota in chronic inflammatory disease 2017 May 26 Many benefits provided by the gut microbiota to the host rely on its intricate interactions with host cells. Perturbations of the gut microbiota, termed gut dysbiosis, affect the interplay between the gut microbiota and host cells, resulting in dysregulation of inflammation that contributes to the pathogenesis of chronic inflammatory diseases, including inflammatory bowel disease, multiple sclerosis, allergic asthma and rheumatoid arthritis. In this review, we provide an overview of how gut bacteria modulates host metabolic and immune functions, summarize studies that examined the roles of gut dysbiosis in chronic inflammatory diseases, and finally discuss measures to correct gut dysbiosis as potential therapeutics for chronic inflammatory diseases.
28202745 Plasma Levels of Eicosapentaenoic Acid Are Associated with Anti-TNF Responsiveness in Rheu 2017 Jun OBJECTIVE: To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF-driven Th17 cell differentiation. METHODS: Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured. CD4+CD25- T cells and monocytes were purified from the blood of healthy donors and cocultured in the presence of anti-CD3, with or without etanercept (ETN), eicosapentaenoic acid (EPA), or the control fatty acid, linoleic acid (LA). Expression of interleukin 17 and interferon-γ was measured by intracellular staining and flow cytometry. RESULTS: Plasma PC EPA levels and the EPA/arachidonic acid ratio correlated inversely with change in the Disease Activity Score at 28 joints (DAS28) at 3 months (-0.51, p = 0.007 and -0.48, p = 0.01, respectively), indicating that higher plasma EPA was associated with a greater reduction in DAS28. Plasma PC EPA was positively associated with European League Against Rheumatism response (p = 0.02). An increase in Th17 cells post-therapy has been associated with nonresponse to anti-TNF. ETN increased Th17 frequencies in vitro. Physiological concentrations of EPA, but not LA, prevented this. CONCLUSION: EPA status was associated with clinical improvements to anti-TNF therapy in vivo and prevented the effect of ETN on Th17 cells in vitro. EPA supplementation might be a simple way to improve anti-TNF outcomes in patients with RA by suppressing Th17 frequencies.
29213000 [A methotrexate-associated lympholiferative disorder patient with gastrointestinal perfora 2017 A 70-year-old woman was diagnosed with chronic rheumatoid arthritis and treated with methotrexate and prednisolone. She visited our hospital to determine the cause of her continuous fatigue and fever for the past three weeks. She consumed no food orally and was provided antibiotics because free air was found on computed tomography (CT). Intraperitoneal small lymphadenopathy and swelling of both adrenal glands was also found on CT, and MTX-associated lymphoproliferative disorder (MTX-LPD) was suspected. Am adrenal gland biopsy showed diffuse large B-cell lymphoma (DLBCL) associated with MTX-LPD. The causes of gastrointestinal perforation with collagen diseases have been reported to be functional gastrointestinal disorders with collagen diseases like amyloidosis, gastrointestinal infections in immunocompromised patients, and side effects of medication, such as steroids or NSAIDs and MTX. MTX-LPD is an uncommon side effect of methotrexate. To ensure its appropriate diagnosis and treatment, it is important to improve the degree of recognition of MTX-LPD, and a prompt response is needed.
27788297 Progressive Decline of Lung Function in Rheumatoid Arthritis-Associated Interstitial Lung 2017 Mar OBJECTIVE: Interstitial lung disease (ILD) is associated with substantial morbidity in rheumatoid arthritis (RA), but very little is known about its long-term progression. This study was undertaken to investigate the progression of pulmonary disease using a large single-center cohort of patients with RA-associated ILD. METHODS: Records of all patients with RA-associated ILD seen at Mayo Clinic between 1998 and 2014, with at least 4 weeks follow-up and at least 1 pulmonary function test, were identified and manually screened for study inclusion. Progression was defined as a diffusing capacity for carbon monoxide (DLco) <40% predicted (or patients whose illness was too advanced to undergo screening) or a forced vital capacity (FVC) <50% predicted. Time to progression was analyzed using the Kaplan-Meier method. RESULTS: Of the 167 patients included in the study, 81 (49%) were female, with a mean ± SD age of 67 ± 10 years at diagnosis of ILD. Median follow-up time from diagnosis of ILD was 3.3 years (range 0.01-14.8). One-third of the patients required supplemental oxygen, 40% developed DLco <40% predicted, and 22% developed FVC <50% predicted within 5 years after ILD diagnosis. Usual interstitial pneumonia (UIP) versus nonspecific interstitial pneumonia (NSIP) was a risk factor for DLco progression (hazard ratio 3.29 [95% confidence interval 1.28-8.41]). Lower DLco and FVC at baseline increased the risk for progression to DLco <40% predicted and FVC <50% predicted, and higher rates of change in the first 6 months also increased the risk of progression. CONCLUSION: Progressive loss of pulmonary function is common in RA-associated ILD and is worse in patients with UIP than in those with NSIP. Predictors of progression in patients with RA-associated ILD may aid clinicians in identifying patients at highest risk for progression of ILD.
28257609 Albuminuria in Rheumatoid Arthritis: Associations With Rheumatoid Arthritis Characteristic 2017 Dec OBJECTIVE: Albuminuria is a marker for subclinical cardiovascular disease (CVD) in the general population. It is uncertain whether this association is present in patients with rheumatoid arthritis (RA), a population with increased atherosclerosis and CVD events. METHODS: Urine albumin from a spot morning collection was measured, and the urine albumin-to-creatinine ratio (uACR) was calculated for RA patients and a population-based sample of demographically matched non-RA controls. Associations of elevated uACR (≥25 mg/gm for women and ≥17 mg/gm for men) with CVD risk factors and measures of atherosclerosis (coronary artery calcification, ultrasound-determined maximal intima-media thickness of the common carotid artery and internal carotid artery [ICA], and the presence of focal plaque in the ICA) were compared cross-sectionally according to RA status. RESULTS: We compared 196 RA patients with 271 non-RA controls. Elevated uACR was found in 18% of the RA patients compared with 17% of the controls (P = 0.89). After adjustment, RA was associated with 57% lower odds of elevated uACR (P = 0.016). Higher serum creatinine levels and hypertension were both strongly and significantly associated with elevated uACR in the control group but not in the RA group (both P for interaction < 0.05). Among RA characteristics, the adjusted prevalence of elevated uACR among those treated with tumor necrosis factor inhibitors was less than half that among those not so treated (9% versus 20%, respectively; P = 0.047). CONCLUSION: There was no association in the RA group of elevated uACR with measures of atherosclerosis or with several key cardiometabolic risk factors, which suggests a lower usefulness of elevated uACR as an indicator of subclinical CVD in RA.
29041949 Incretins in patients with rheumatoid arthritis. 2017 Oct 17 BACKGROUND: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. METHODS: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. RESULTS: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (β coefficient 46, 95% CI 6-87, p = 0.026) and Clinical Disease Activity Index (β coefficient 7.74, 95% CI 1.29-14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with β-cell function (HOMA2 of β-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. CONCLUSIONS: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.
28766389 Pharmacokinetics, efficacy and safety of the rituximab biosimilar CT-P10. 2017 Sep Rituximab, an anti-CD20 monoclonal antibody, is a key therapeutic in the treatment of B cell lymphomas and rheumatoid arthritis (RA). Global rates of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and RA are increasing, with a concomitant rise in individual and overall treatment costs. As such, biosimilar development may help facilitate greater access to treatment. The rituximab biosimilar CT-P10 (Truxima®) has recently received approval in Europe and South Korea for all indications held by reference rituximab (RTX). Areas covered: Here, the unmet needs and current market in the treatment of NHL, CLL and RA are outlined, followed by a comprehensive examination of the analytical, pre-clinical and clinical data demonstrating the equivalence and similarity of CT-P10 to RTX including with respect to pharmacokinetics, efficacy, safety and immunogenicity. Expert commentary: The rising treatment costs of NHL, CLL and RA pose a challenge to constrained healthcare budgets worldwide. Biosimilars may provide an effective solution to this conundrum. CT-P10 is equivalent to RTX in terms of efficacy and pharmacokinetics, and has a similar safety and immunogenicity profile. Approved in all indications held by RTX, CT-P10 has the potential to reduce treatment costs and thereby increase patient access to rituximab therapy.
29303700 The eumusc.net standards of care for rheumatoid arthritis: importance and current implemen 2018 Mar OBJECTIVES: The eumusc.net standards of care (SOCs) for rheumatoid arthritis (RA) aimed to improve quality of care across Europe. This study investigated importance and implementation of each standard according to patients and health care professionals (HCPs) in the Netherlands and identified barriers towards implementation. METHODS: Dutch patients, rheumatologists and rheumatology nurses rated importance and implementation (0-10 numeric rating scale (NRS); 10=most important/best implemented) for each of the 20 SOCs. A care gap, adjusted for importance, was calculated: (100=highest gap). Statistical differences between a) patients and HCPs and b) subgroups of patients (demographics, health) were tested. Additionally, patients indicated agreement (0-10) with 6 implementation barriers. RESULTS: 386 patients and 91 HCPs were included. Both ranked adequate disease modifying anti-rheumatic drug treatment (9.3(SD1.2), 9.2(SD0.8)), access to care in emergencies (9.2(SD1.2), 9.2(SD1.0)) and regular re-appraisal when treatment fails (9.2(SD1.3), 9.0(SD1.0)) the most important SOCs, and these were among the best implemented (NRS≥8.5) SOCs. After accounting for applicability, patients and HCP identified care gaps for early diagnosis (25.5(SD32.0), 22.3(SD16.3)), availability of a treatment plan (25.1(SD22.7), 25.7(SD18.5)) and patients also for a regular schedule of assessment of disease (28.6(SD25.5)).Patients with poorer health or higher education scored systematically lower on care received while sharing similar priorities. Patients and HCPs considered limited reimbursement of specific health services a main barrier for implementation and patients additionally identified limited time of physicians. CONCLUSIONS: Dutch patients and HCPs overall agreed on priorities in care and found relevant SOCs well implemented. However, suggestions for improvement were raised especially by patients with poorer health and/or higher education.
27715362 Cellular Infiltrate in Rheumatoid Arthritis-associated Paracentral Corneal Ulceration. 2017 Dec PURPOSE: To investigate an immunopathogenesis of central and paracentral corneal ulceration associated with rheumatoid arthritis. METHODS: Sparse infiltrating cells in the ulcer area were identified by immunohistochemistry applied to archived formalin fixed, paraffin embedded tissues that had been recovered from patients undergoing penetrating keratoplasty necessitated by rheumatoid-associated central or paracentral corneal ulceration. RESULTS: Clinically, the ulcers presented as non-infiltrated lesions with a modicum of other ocular inflammation. Sparse T-lymphocytes were consistently identified in the subepithelial areas adjacent to the ulcer, with some neutrophils and macrophages in the stroma. B-lymphocytes were not detected. MHC Class II antigens reactivity was noted on some infiltrating cells and on corneal endothelium of two specimens. CONCLUSIONS: Immunohistochemistry of archival tissue facilitated detection and identification of sparse infiltrate in this infrequent corneal melting. Selective, consistent finding of T-lymphocyte infiltration in the ulcer area supports an immunopathogenesis of this clinical entity.
28397468 Association of Serum Interleukin-28B with Clinical Features, Laboratory Values and Radiogr 2017 Apr 1 BACKGROUND: Interleukin-28B (IL-28B) is a member of the interferon lambda family (also known as type III interferons), it has already been studied in many diseases, but it has almost never been studied in rheumatoid arthritis (RA). With this background, we determined the serum levels of IL-28B in RA patients and investigated its clinical significances. METHODS: IL-28B levels were measured by enzyme-linked immunosorbent assay (ELISA) in 80 RA patients and 80 healthy controls. Radiographs were scored for total Sharp score (TSS). RESULTS: Serum IL-28B levels were significantly lower in the RA than in the control (p = 0.02). Anticyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) were negatively correlated with serum IL-28B levels. There was no association between serum IL-28B levels and TSS at baseline, but there was a significant difference in change of IL-28B during 6 months follow up between progressors and non-progressors. The disease activity of RA patients decreased, but no difference was observed in serum IL-28B levels between before and after disease-modifying anti-rheumatic drugs (DMARDs) therapy. CONCLUSIONS: These findings indicated a role of IL-28B in RA and it may contribute to avoiding osteoclasia in RA patients.
28191607 Retrospective study of the clinical characteristics and risk factors of rheumatoid arthrit 2017 Apr This study aims to explore the clinical characteristics and risk factors of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). This is a retrospective study of 550 patients with RA. All patients underwent chest high-resolution computed tomography (HRCT) scanning. (1) Two hundred thirty-seven out of five hundred fifty (43.1%) patients with RA were diagnose with ILD. 13.5% ILD occurred before RA onset, 69.6% ILD occurred within 10 years of RA onset, and 16.9% ILD occurred more than 10 years after RA onset. (2) The most common chest CT characteristics of RA-ILD included reticular patterns (57.8%), pleural thickening (57%), ground-glass attenuation (53.2%), followed by interlobular septum thickening, nodules, emphysematous bullae, honeycombing, and bronchiectasis. The proportion of the UIP pattern and NSIP on HRCT was 18.6% and 57.8%. (3) RA-ILD was often associated with other lung lesions, including pleural disease, bronchiectasis, and pulmonary hypertension. (4) the comparisons between RA with ILD and RA without ILD showed that male, smoking, age, disease duration, number of swelling joints, globulin levels, erythrocyte sedimentation rate, C-reactive protein levels, lactate dehydrogenase, the positive rate of rheumatoid factor (RF) and the absolute value of RF, forced vital capacity, forced expiratory volume in 1 s, and carbon monoxide diffusion rate, were statistically different (P < 0.05). Logistic regression analysis showed that age, smoking, elevated lactate dehydrogenase, and RF positive were closely correlated to RA-ILD. RA-ILD occurs more often within 10 years of RA onset and coexists with other lung lesions. The elevated lactate dehydrogenase, RF positive, smoking, and advanced age are closely correlated with RA-ILD.
29080328 Clinical and functional significance of STEAP4-splice variant in CD14(+) monocytes in pati 2018 Mar Tumour necrosis factor alpha (TNF)-α-induced adipose-related protein (TIARP) is a negative regulator of inflammation in arthritis model mice. In humans, six-transmembrane epithelial antigen of prostate 4 (STEAP4) (human counterpart of TIARP) is also expressed in CD14(+) monocytes from patients with rheumatoid arthritis (RA). Recently, highly levels of exon 3-spliced variant STEAP4 (v-STEAP4) expression have been observed in porcine lung. The aim of this study is to elucidate the expression and functional role of v-STEAP4, comparing it with that of STEAP4, in the pathogenesis of arthritis. We identified v-STEAP4 in CD14(+) cells. The expression of STEAP4 and v-STEAP4 was higher in patients with RA than in healthy participants. We also found that STEAP4 and v-STEAP4 were correlated positively with C-reactive protein and that their expression was decreased after treatment with an interleukin (IL)-6 antagonist in patients with RA. To investigate further the role of STEAP4 and v-STEAP4, we produced STEAP4 and v-STEAP4 over-expressing human monocytic cell lines (THP-1) for functional analysis. In the v-STEAP4 over-expressing cells, the production of IL-6 was suppressed significantly, but TNF-α was increased significantly through lipopolysaccharide (LPS) stimulation. Immunoblot analysis revealed that phosphorylated (p-)nuclear factor kappa B (NF-κB) was increased after LPS stimulation and degradation of nuclear factor kappa B inhibitor alpha (IκBα) was sustained, whereas p-signal transducer and activator of transcription 3 (STAT-3) was decreased with v-STEAP4. We identified specific up-regulation of v-STEAP4 in RA monocytes. V-STEAP4 might play a crucial role in the production of TNF-α and IL-6 through NF-κB and STAT-3 pathways, resulting in the generation of RA.
28760047 Demographics, treatment patterns, and healthcare utilization and cost of repository cortic 2017 Nov OBJECTIVE: To evaluate healthcare resource utilization (HRU) and costs among patients who initiated repository corticotropin injection (RCI; H.P. Acthar Gel) treatment for rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). METHODS: Patients aged ≥18 years with ≥2 diagnoses for either RA or SLE between July 1, 2006 and April 30, 2015 were identified in the HealthCore Integrated Research Database. Index RCI date was the earliest date of a medical or pharmacy claim for RCI after diagnosis. Baseline characteristics, pre- and post-initiation HRU and costs were assessed using descriptive statistics. RESULTS: This study identified 180 RA patients (mean age = 60 years, 56% female) and 29 SLE patients (mean age = 45 years, 90% female) who initiated RCI. First RCI use averaged 7.1 and 22.6 months after the initial RA and SLE diagnosis, respectively. After RCI initiation, RA patients incurred significantly lower per-patient-per-month (PPPM) all-cause medical costs ($1,881 vs $682, p < .01) vs the pre-initiation period, driven by lower PPPM hospitalizations costs ($1,579 vs $503, p < .01). Overall PPPM healthcare costs were higher ($2,751 vs $5,487, p < .01) due to higher PPPM prescription costs ($869 vs $4,805, p < .01). Similarly, SLE patients had decreased PPPM hospitalization costs ($3,192 vs $799, p = .04) and increased PPPM prescription costs ($905 vs $7,443, p < .01) after initiating RCI; the difference in overall PPPM healthcare costs was not statistically significant likely, due to small sample size. CONCLUSION: This study, across a heterogeneous population of variable disease duration, described clinical and healthcare utilization and costs of RA and SLE patients initiating RCI in a real-world setting. We observed that patients receiving RCI had lower utilization and costs for medical services in both disease populations, which partially offset the increased prescription costs by 30% and 37%. Future research is needed to explore factors associated with RCI initiation and its impact on long-term outcomes.
28836879 Outcome of the Sauvé-Kapandji procedure for distal radioulnar joint disorder with rheumat 2018 May OBJECTIVES: We performed the Sauvé-Kapandji procedure for treating disorders of the distal radioulnar joint (DRUJ) in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). This study aimed to compare and clarify the results of the SK procedure between RA and OA patients. We report the one-year follow-up results of patients who underwent the SK procedure to correct the DRUJ disorder caused by RA or OA. METHODS: The study included 22 wrists of 19 patients with RA and 10 wrists of nine patients with OA. Pain, grip strength and range of motion of the wrist were examined clinically. For the evaluation of the stability of the carpus, ulnar stump and bone union, parameters were measured using radiographs. Shortened disabilities of the arm, shoulder and hand questionnaire (QuickDASH) was used for functional evaluation. RESULTS: Wrist pain reduced in all cases, and bone union was achieved in all wrists. The QuickDASH score significantly improved in both patients with RA and OA. In patients with RA, the range of motion increased significantly with regard to supination but decreased significantly with regard to palmar flexion. Carpal alignment and ulnar stump stability were maintained well at one-year follow-up. CONCLUSION: The Sauvé-Kapandji procedure for treating disorders of the distal radioulnar joint DRUJ showed good results clinically and radiographically, irrespective of RA or OA.