Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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32598674 | [Level of N-terminal fragment of brain natriuretic peptide progenitor and atherosclerotic | 2019 May 15 | The high prognostic significance of the concentration of the N-terminal - pro-B-type natriuretic peptide (NT-proBNP) in the development of cardiovascular diseases (CVD) was identified for rheumatoid arthritis (RA) and general populations. AIM: to investigate the significance of NT-proBNP level in patients (pts) with RA with the ineffectiveness and/or intolerance of basic anti - inflammatory therapy; compare the level of NT-proBNP with atherosclerotic lesion of the brachiocephalic arteries (BCA), traditional risk factors and inflammatory markers. MATERIALS AND METHODS: The investigation enrolled 28 pts (24women/4men) with the lack of efficacy/resistance and/or intolerance of basic anti - inflammatory drugs (DMARDs); median age was 55 [46; 61] years, median disease duration 114 [60; 168] month; DAS28 6,2 [5.1; 7.0]; SDAI 35.0[23.9; 51.0], CDAI 30.0[21.0; 42.0], serum positivity for rheumatoid factor (RF) (100%)/anti - cyclic citrullinated peptide antibodies (ACCP) (86%). The study did not include RA pts with congestive heart failure. High incidence of traditional risk factors was found in RA pts: arterial hypertension - in 75%, dyslipidemia - 61%, smoking - 17%, overweight - 61%, family history of cardiovascular diseases - 36%, hypodynamia - 68%. Coronary artery disease was diagnosed in 11% RA pts. Lack of efficacy of 3 or more DMARDs was found in 46% of pts, intolerance to previous therapy with DMARDs - in 54% pts. 47% were receiving methotrexate (20 [18; 25] mg/week), 11% - leflunomide, 7% - sulfasalazine, 46% - glucocorticoids, 75% - non - steroidal anti - inflammatory drugs. The control group consisted of 20 healthy donors, comparable to pts by age and sex. Serum levels of of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland). The determination of the intima - media thickness (IMT) BCA were assessed from duplex scanning. Atherosclerotic lesion of BCA was assessed by the presence of atherosclerotic plaque (IMT ≥1.2 mm). RESULTS: NT-proBNP concentrations in RA pts proved to be higher (78.7 [41.4; 101.3] pg/ml) than those in the control group (55.3 [36.6; 67.3] pg/ml, p100 pg/ml - 1 group (n=6) and ≤100 pg/ml - 2 group (n=22). Groups of RA pts did not differ in gender, age, activity of RA, frequency of detection of traditional risk factors. Atherosclerotic lesion of the BCA was detected in 3 (50%) pts of the 1 group and in 8 (36%) pts of the 2 group (p>0.05). In RA pts the level of NT-proBNP correlated with age (r=0.39; p. | |
33087004 | A case of acute diffuse large B cell lymphoma in an anti-human T-cell leukaemia virus type | 2020 Jul | A 70-year-old woman was hospitalised due to jaundice and fever. She was diagnosed with rheumatoid arthritis (RA) at 54 years of age. Treatment with methotrexate (MTX) was successful, and her RA was in remission. Five weeks before the hospitalisation, she was diagnosed with optic neuritis due to a decline in the visual acuity of the right eye. She was treated with methylprednisolone pulse therapy, followed by prednisolone (PSL), before the hospitalisation, which were not effective. Blood tests showed increased C-reactive protein (CRP) levels, liver injury, and thrombocytopenia. Abdominal echo revealed numerous enlarged lymph nodes in the hepatic portal region. Malignant lymphoma was suspected due to high serum levels of soluble interleukin-2 receptor. None of the treatments were effective, and she died on the fifth hospital day. Diffuse large B cell lymphoma was diagnosed during the autopsy, which showed infiltration of CD20-positive atypical lymphocytes in almost all organs. Since she was taking MTX, she was diagnosed with immunosuppressive drug-associated lymphoproliferative disease (LPD). Anti-human T-cell leukaemia virus type 1 (HTLV-1) antibody was detected in her serum after her death; however, adult T cell leukaemia/lymphoma was not observed. LPD develops during the treatment of RA with disease modifying anti-rheumatic drugs; however, a rapid clinical course leading to death is rarely observed. Previous reports suggest that T cell dysregulation observed in HTLV-1 may contribute towards the development of B cell lymphoma. We have discussed the possible roles of HTLV-1 in LPD development in this case. | |
30528678 | New concepts to reduce glucocorticoid toxicity. | 2019 Nov | 70 years after their first use, low-dose glucocorticoids are a common part of pharmacological rheumatoid arthritis treatment. This is due to their well-proven capacities in symptom severity and disease activity reduction, in particular when combined with a disease-modifying anti-rheumatic drug, such as methotrexate. Nevertheless, glucocorticoid administration, in long-term especially, is also seen critically because of its potential adverse conditions. In order to achieve a reduction in treatment-related adverse events, modern therapy regimes should take into consideration patients' risk factors and therefore be individual. The Glucocorticoid Toxicity Index is a method to measure side effects of glucocorticoid therapy objectively and will be central in future studies comparing different therapy regimes. Such a new therapy regime is modified-release prednisone, which - thanks to a different time of liberation - seems to capable of reducing morning stiffness much more effectively than conventional prednisone, whilst showing similar properties in disease activity reduction and safety. Still, confirmation of these first data in further trials will be necessary. Eventually, other innovative concepts are liposomal glucocorticoids, dissociated agonists of glucocorticoid receptors and intramuscular application of glucocorticoids. Though these approaches appear to be promising, additional research will be required. | |
31921217 | Effects of Methotrexate Alone or Combined With Arthritis-Related Biotherapies in an in vit | 2019 | Background: Methotrexate (MTX) at low dose is a key drug for rheumatoid arthritis (RA). MTX is widely used alone or combined with biologics or steroids. The aim was to study its effects on cytokine production using an in vitro model with synoviocytes interacting with peripheral blood mononuclear cells (PBMC) to reproduce the interactions in RA synovium. Methods: Activated-PBMC were co-cultured with RA synoviocytes during 48 h. A dose-response of MTX was tested and different biotherapies (Infliximab, Tocilizumab, Abatacept and Rituximab) were added alone or in combination with MTX. Cytokine production (IL-17, IL-6, IL-1β, IFN-γ, and IL-10) was measured by ELISA. These results were compared with those obtained with steroids. Results: MTX alone had a modest inhibitory effect on cytokine production compared to steroids. The most effective concentration was one of the lowest, 0.01 μg/ml, as for steroids. Infliximab was the most active biotherapy (p ≤ 0.05 for all cytokines) followed by Tocilizumab (p ≤ 0.05 for all cytokines except IL-6). Abatacept and Rituximab had a more restricted effect on cytokines (p ≤ 0.05 for IL-1β and IFN-γ). The combination MTX/biotherapies did not increase significantly the inhibition of cytokine production but some specific inhibitory effects were observed with Infliximab on IL-17 and IL-6, and with Abatacept and Rituximab on IL-1β. Conclusion: Low dose of MTX was at least as effective as high dose. The effects of the combination with biotherapies showed an important level of heterogeneity between the levels of some specific cytokines and the degree of inhibition with drugs. | |
31393634 | Belimumab treatment in rhupus: A case report with severe skin involvement. | 2019 Sep | Patients with rhupus characteristically exhibit symmetric polyarthritis and clinical manifestations suggestive of systemic lupus erythematosus (malar rash, photosensitivity, hematological manifestations, serositis, and/or skin involvement) and positive anti-dsDNA. Treatment is unclear and it can include disease-modifying rheumatic drugs like hydroxyl chloroquine, or methotrexate or, in refractory cases, rituximab or abatacept. We report a case of 31-year-old female who present with rhupus with skin acute lesions treated with belimumab. This is the first case of rhupus treated with this drug described in the literature. | |
30408585 | Arthritis in primary Sjögren's syndrome: Characteristics, outcome and treatment from Fren | 2019 Jan | OBJECTIVE: To describe the characteristics and the outcome of primary Sjögren Syndrome (pSS) associated arthritis and to compare the efficacy of different therapeutic regimen. METHODS: We conducted a retrospective study using Club Rhumatisme and Inflammation (CRI) and French Internal Medicine Society (SNFMI) networks. All patients with a diagnosis of pSS and at least one episode of clinical and/or echographic synovitis were included. Patients with synovitis (cases) were compared to pSS patients without synovitis (controls). RESULTS: 57 patients (93% women) were included with a median age of 54 years [45-63]. Patients with synovitis had more frequently lymph node enlargement (12.3% vs. 1.8%, p = .007) and a higher ESSDAI score (8 [6-12] vs. 2 [1-4], p < .0001). There was no difference concerning CRP levels, rheumatoid factor and cyclic citrullinated peptide (CCP)-antibodies positivity. Among 57 patients with synovitis, 101 various treatment courses have been used during the follow-up of 40 [22.5-77] months. First treatment course consisted in steroids alone (3.5%), steroids in association (79%) with hydroxychloroquine (HCQ) (49%), methotrexate (MTX) (35%), rituximab (RTX) (5.3%) or other immunosuppressive drugs (7%). HCQ, MTX, and RTX were associated with a significant reduction of tender and swollen joint count, and a significant steroids-sparing effect. No difference could be shown for the joint response between these treatment regimens. CONCLUSION: pSS articular manifestations may include synovitis which could mimic rheumatoid arthritis but differ by the absence of structural damage. Even if the use of HCQ, MTX, and RTX seem to be effective for joint involvement, the best regimen remains to be determined. | |
31491879 | Different Original and Biosimilar TNF Inhibitors Similarly Reduce Joint Destruction in Rhe | 2019 Sep 5 | The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept, adalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have been compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not been compared directly to each other or to an otherwise untreated placebo control. The present analysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic joint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network meta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with controls, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in the network. The previously untested comparison with placebo was performed to estimate not only the effect relative to another drug, but also the absolute attainable effect. Compared to placebo there was a highly significant inhibitory effect on joint destruction of infliximab, etanercept, adalimumab, certolizumab, and golimumab, which was about 0.9% per year as monotherapy and about 1.2% per year when combined with MTX. Although significantly better than MTX and placebo, golimumab seemed inferior to the remaining TNFis. There was no difference between original reference drugs (Remicade, Enbrel) and the almost identical copy drugs (biosimilars). | |
30822342 | SNR analysis of contrast-enhanced MR imaging for early detection of rheumatoid arthritis. | 2019 | OBJECTIVE: To investigate whether signal to noise (SNR) analysis of contrast-enhanced MRI gives additional benefit for early disease detection by Magnetic Resonance Imaging (MRI) of experimental rheumatoid arthritis (RA) in a small animal model. METHODS: We applied contrast-enhanced MRI at 7T in DBA mice with or without collagen-induced arthritis (CIA). Clinical score, OMERACT RAMRIS analysis and analysis of signal to noise ratios (SNR) of regions of interest in RA bearing mice, methotrexate/methylprednisolone acetate treated RA and control animals were compared with respect to benefit for early diagnosis. RESULTS: While treated RA and control animals did not show signs of RA activity in any of the above-mentioned scoring methods at any time point analyzed, RA animals revealed characteristic signs of RA in RAMRIS at the same time point when RA was detected clinically through scoring of the paws. The MR-based SNR analysis detected signs of synovitis, the earliest indication of RA, not only in late clinical stages, but also at an early stage when little or no clinical signs of RA were present in CIA animals and RAMRIS did not allow a distinct early detection. CONCLUSION: SNR analysis of contrast-enhanced MR imaging provides additional benefit for early arthritis detection in CIA mice. | |
31651077 | Metabolomic Profiling to Identify Molecular Biomarkers of Cellular Response to Methotrexat | 2020 Jan | Variation in methotrexate (MTX) efficacy represents a significant barrier to early and effective disease control in the treatment of autoimmune arthritis. We hypothesize that the utilization of metabolomic techniques will allow for an improved understanding of the biochemical basis for the pharmacological activity of MTX, and can promote the identification and evaluation of novel molecular biomarkers of MTX response. In this work, erythroblastoid cells were exposed to MTX at the physiologic concentration of 1,000Â nM and analyzed using three metabolomic platforms to give a broad spectrum of cellular metabolites. MTX pharmacological activity, defined as cellular growth inhibition, was associated with an altered cellular metabolomic profile based on the analysis of 724 identified metabolites. By discriminant analysis, MTX treatment was associated with increases in ketoisovaleric acid, fructose, galactose, and 2-deoxycytidine, and corresponding reductions in 2-deoxyuridine, phosphatidylinositol 32:0, orotic acid, and inosine monophosphate. Inclusion of data from analysis of folate metabolism in combination with chemometric and metabolic network analysis demonstrated that MTX treatment is associated with dysregulated folate metabolism and nucleotide biosynthesis, which is in line with its known mechanism of action. However, MTX treatment was also associated with alterations in a diversity of metabolites, including intermediates of amino acid, carbohydrate, and lipid metabolism. Collectively, these findings support a robust metabolic response following exposure to physiologic concentrations of MTX. They also identify various metabolic intermediates that are associated with the pharmacological activity of MTX, and are, therefore, potential molecular biomarker candidates in future preclinical and clinical studies of MTX efficacy in autoimmune arthritis. | |
30418117 | The VICM biomarker is released from activated macrophages and inhibited by anti-GM-CSFRα- | 2019 Jan | OBJECTIVES: Macrophages possess widespread pro-inflammatory, destructive, and remodelling capabilities that can critically contribute to acute and chronic diseases, such as rheumatoid arthritis (RA). Continuous monitoring and measurement of selective counteraction of macrophage activity in patients require a sensitivity and non-invasive marker. We characterised the VICM (citrullinated and MMP degraded vimentin fragment) biomarker by investigating the release from in vitro activated macrophages and by monitoring the change in serum levels after treatment with the anti-GM-CSFRα-mAb (mavrilimumab). METHODS: Peripheral blood mononuclear cells were isolated, and lipopolysaccharide (LPS) was used to activate the macrophages and calcium chloride (CaCl2) was used to facilitate the citrullination process of vimentin. Supernatants, cell lysates, was collected and analysed by ELISA, and western blotting. RA patients were treated with mavrilimumab+methotrexate or methotrexate alone in a phase 2b study (NCT01706926) once every two weeks for 24 weeks. Serum levels of VICM were measured at baseline and multiple time points post-treatment. In addition, whole blood expression of peptidylarginine deiminase-2 (PAD-2) and matrix metalloproteinase-9 (MMP-9) transcripts were tested by quantitative reverse transcriptase PCR assays at day 0 and day 169 post-treatment. RESULTS: VICM levels were significantly higher at day 5 and 8 in supernatants of activated macrophages compared to controls (p<0.01), which was confirmed by Western blot. In RA patients, VICM correlated with disease activity (DAS28), modified total sharp score (mTSS), joint space narrowing (JSN), joint erosions and CRP at baseline. VICM was dose-dependently and significantly (p<0.01) inhibited by mavrilimumab. This suppression of VICM serum levels was supported by a decreased expression of PAD2 and MMP9 transcripts in patients treated with mavrilimumab. CONCLUSIONS: These data verified that VICM is released by activated macrophages. Treatment of RA patients with mavrilimumab significantly reduced release of VICM and peptidylarginine deiminases-2 (PAD-2) gene expression indicating that mavrilimumab indeed is targeting activated macrophages and that VICM may be a novel blood-based marker of anti-GM-CSF response. | |
30227223 | Circadian rhythms and rheumatoid arthritis. | 2019 May | Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of pro-inflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the night (night release). The impressive positive results observed in RA patients treated with modified-night release prednisone with a low-dose chronotherapy, seem applicable even for other agents such as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained by the night time daily administration of methotrexate. Interestingly, a very recent study showed that methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is promising. | |
31183624 | Clinical characteristics of scleritis patients with emphasized comparison of associated sy | 2019 Sep | PURPOSE: We evaluated patient profiles, clinical features, associated systemic diseases, treatment modalities, and ocular complications in cases of scleritis and episcleritis. STUDY DESIGN: Retrospective. METHODS: Clinical data of 128 patients referred to the ophthalmology clinic at Jichi Medical University Hospital during the 4-year period from April 2011 to March 2015, and diagnosed with scleritis or episcleritis were examined. Gender, average onset age, unilateral or bilateral manifestation, classification type, associated systemic diseases, and treatments were retrospectively investigated. RESULTS: The cohort consisted of 57 men and 71 women. Average onset age was 54.3 ± 17.4 years. Diffuse anterior scleritis was the most common type. It was noted in 43 (32.8%) patients, followed by episcleritis in 35 (27.3%), nodular anterior scleritis in 23 (18.0%), necrotizing anterior scleritis in 22 (17.2%), and posterior scleritis in 6 (4.7%). Eighteen (81.8%) of 22 patients with necrotizing anterior scleritis required some type of systemic medication, including corticosteroid, cyclophosphamide, cyclosporine, azathioprine, methotrexate, or rituximab administration. Forty (31.3%) had associated systemic diseases, which included 10 with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and 8 with rheumatoid arthritis (RA). Patients with ANCA-associated vasculitis had a tendency to develop scleritis first and had significantly worse visual prognoses compared to those with RA. CONCLUSIONS: Approximately 30% of the patients with scleritis and episcleritis had complications involving systemic diseases, including ten patients with ANCA-associated vasculitis and 8 with RA. ANCA-associated vasculitis was more often diagnosed after scleritis and patients suffered poorer visual prognoses than those with RA. | |
30557057 | Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid | 2020 Jan | Objectives: Comorbidities and conventional risk factors influence the prognosis of patients with rheumatoid arthritis (RA). We investigated whether liver fibrosis burden is associated with all-cause mortality in patients with RA.Methods: A total of 2812 patients with RA were retrospectively selected and reviewed. Liver fibrosis was assessed using the fibrosis-4 index (FIB-4) [age (years)× aspartate aminotransferase level (IU/L)/platelet count (10(9)/L)/√alanine aminotransferase (IU/L)].Results: The mean patient age was 51.5 years (482 men and 2330 women). The mean erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and FIB-4 were 43.5 mm/h, 9.0 mg/L, and 1.0, respectively. Methotrexate was used in 2524 (89.9%) patients, and biological or targeted synthetic disease-modifying antirheumatic drugs were used in 310 (11.0%) patients. During the follow-up period (mean 93.7 months), 89 (3.2%) patients died. Deceased patients had a significantly higher age (mean 64.4 vs. 51.1 years); frequency of male sex (31.5% vs. 16.7%), hypertension (HTN; 40.4 vs. 18.5%), and diabetes mellitus (DM; 25.8% vs. 7.7%); ESR (mean 57.1 vs. 43.0 mm/h); CRP (mean 16.9 vs. 8.7 mg/L); and FIB-4 (mean 1.5 vs. 1.0) (all p < .05) than the survivors. On multivariate analysis, higher FIB-4 was found to be independently associated with a higher rate of all-cause mortality (hazard ratio =1.130, p = .004), together with male sex, HTN, DM, ESR, and intensity of glucocorticoid exposure, whereas the use of methotrexate was independently protective (all p < .05).Conclusion: Besides conventional risk factors, fibrotic burden, assessed using FIB-4, might be useful for risk stratification of patients newly diagnosed as having RA. | |
30168274 | Influence of methotrexate on gastrointestinal symptoms in patients with rheumatoid arthrit | 2019 Feb | AIM: This study aimed to determine the influence of methotrexate (MTX) on gastrointestinal (GI) symptoms in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study examined 529 consecutive patients with RA receiving oral MTX in our department between April 1 and September 30, 2017. GI symptoms were evaluated by the Gastrointestinal Symptom Rating Scale (GSRS); a score of ≥2 was considered "symptomatic." Prevalence of GI symptoms was compared between patients receiving ≤8 mg/wk (low-dose) vs >8 mg/wk (high-dose) of MTX. RESULTS: Of our study population, 313 (59%) received low-dose MTX at a median (interquartile range) dose of 6 (6-8) mg/wk, whereas 216 (41%) received high-dose MTX at a median dose of 12 (10-12) mg/wk. Relative to the low-dose MTX group, the high-dose MTX group exhibited a higher prevalence of reflux (32% vs 24%, P = 0.043) and abdominal pain (28% vs 18%, P = 0.007). There was no significant group-dependent difference in the prevalence of indigestion, diarrhea or constipation. Multivariate logistic regression analysis revealed that high-dose MTX (>8 mg/wk) was independently associated with reflux (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.07-2.43) and abdominal pain (OR: 1.60, 95% CI: 1.04-2.43), and that the ORs for reflux and abdominal pain among those receiving high-dose MTX (>8 mg/wk) were similar to those using nonsteroidal anti-inflammatory drugs. CONCLUSION: High-dose MTX is independently associated with the prevalence of upper GI symptoms in Japanese patients with RA. | |
31366819 | Serum Soluble Interleukin-2 Receptor Is a Biomarker for Pneumocystis jirovecii Pneumonia a | 2019 Jul | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy. | |
30411174 | Should a patient with rheumatoid arthritis be a kidney donor? | 2019 Jan | We cared for a woman with sero-positive rheumatoid arthritis (RA), in clinical remission on oral methotrexate (MTX) and hydroxychloroquine, who wished to donate a kidney to a brother with end-stage renal disease (ESRD). We could find scant literature about this unusual clinical circumstance, and therefore review pertinent aspects of renal disease in RA, perioperative medical management, maintenance of disease remission, outcomes for RA patients who have donated kidneys, and relevant ethical issues. Renal complications in RA are not uncommon, with as many as 50% of patients at risk of reduced eGFR. This reflects anti-rheumatic and analgetic medication use (non-steroidal anti-inflammatory drugs, acetaminophen, DMARDs [cyclosporine and, historically, D-penicillamine and gold compounds], and others), glomerulitis, interstitial nephritis, complicating Sjogren's syndrome, vasculitis, or amyloidosis, and/or emergence of an "overlap" syndrome or other rheumatic disorder. The literature suggests that MTX need not be interrupted for surgery. The risk of perioperative infection to our patient would be low and remission should be sustained. We are aware of one study of six patients with RA who donated kidneys; they experienced no complications, ESRD, or deaths after a median follow-up of 8.2Â years. Our ethical responsibilities are to balance patient autonomy of decision-making while assuring clinical beneficence and minimizing potential maleficence. Our perspective was that it would not be unreasonable to support this patient donating a kidney if, when fully informed, that remained her wish. | |
30246572 | The time-sequential changes of risk factors for adult T-cell leukemia development in human | 2019 Sep | Objective: This study aimed to investigate the time-sequential changes of risk factors for adult T-cell leukemia (ATL) development in human T-cell leukemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Methods: HTLV-1 infection was screened using particle agglutination assay and confirmed via western blotting in 365 RA patients. Twenty-three HTLV-1-positive RA patients were included in the study cohort. Blood samples were obtained from these patients at each observation time point. The values of HTLV-1 proviral load (PVL) and serum soluble IL-2 receptor (sIL2-R), which are risk factors for ATL development, were measured using real-time PCR and enzyme immunoassay, respectively. Results: The study cohort comprised 79 person-years. The median HTLV-1 PVL and sIL2-R values of the HTLV-1-positive RA patients were 0.44 copies per 100 white blood cells (WBCs) and 406 U/mL, respectively. Three HTLV-1-positive RA patients showed a high PVL value. No remarkable changes were observed in the PVL and sIL2-R values during the observation period. However, one elderly HTLV-1-positive RA patient who had a high PVL value developed ATL during treatment with methotrexate and infliximab. Conclusion: A thorough clinical assessment of the risk factors for ATL development may be necessary in daily clinical practice for RA patients in HTLV-1-endemic areas in Japan. | |
30836801 | Radiographic and clinical outcomes following etanercept monotherapy in Japanese methotrexa | 2020 Mar | Objectives: Compare outcomes with methotrexate (MTX) or etanercept (ETN) monotherapy in Japanese patients with active rheumatoid arthritis (RA) who were MTX-naïve or with intolerance or inadequate response to prior MTX (MTX-IR).Methods: Post hoc analysis of a phase 3 study comparing MTX, ETN 10 mg twice weekly, and ETN 25 mg twice weekly in Japanese patients with RA. Disease activity was evaluated using American College of Rheumatology (ACR) scores and 28-joint Disease Activity Score (DAS28), radiographic progression evaluated using van der Heijde's modified Total Sharp Score (mTSS), and functional status evaluated using Health Assessment Questionnaire Disability Index (HAQ-DI).Results: Among MTX-naïve and MTX-IR patients, greater proportions of those randomized to either ETN group achieved ACR20, ACR50, ACR70, DAS28 ≤3.2 or <2.6, clinically relevant inhibition of mTSS changes, and reductions in HAQ-DI compared with MTX at the majority of time points. There were very few clinically meaningful differences between ETN groups for any of the variables evaluated.Conclusion: ETN monotherapy was more effective than MTX in both MTX-naïve and MTX-IR patients, with very few clinically meaningful differences between ETN 10 mg and ETN 25 mg when given twice weekly. The relative benefits of ETN were greater in MTX-naïve patients than MTX-IR patients.ClinicalTrials.gov identifierNCT00445770. | |
28919284 | MMP-8 and TIMP-1 are associated to periodontal inflammation in patients with rheumatoid ar | 2019 Jun | BACKGROUND: Aim of this cross-sectional study was the investigation of associations between different rheumatoid arthritis (RA)-related blood parameters and periodontal condition as well as selected periodontal pathogenic bacteria in RA patients under methotrexate (MTX) immunosuppression. METHODS: Periodontal probing depth (PPD), bleeding on probing (BOP) and clinical attachment loss (CAL) were assessed. Periodontal condition was classified into: no/mild and moderate or severe periodontitis (P). Prevalence of selected periodontal pathogenic bacteria and concentration of matrix metalloproteinase 8 (MMP-8) was assessed from the gingival crevicular fluid (GCF) using PCR and ELISA, respectively. Blood samples were analyzed for the concentration of selected rheumatoid parameters. STATISTICAL ANALYSIS: t-test, Mann-Whitney-U-Test, exact Fisher tests or chi square test (p < 0.05). RESULTS: Fifty-six patients (mean age 55.07 years, 34 P, 22 no P) were included. While prevalence of periodontal pathogenic bacteria was higher in P patients, no substantial association of bacteria with blood parameters was found. In periodontal diseased participants, MMP-8 concentration in GCF (6.22 ± 7.01 vs. 15.99 ± 13.49; p < 0.01) and blood (2.60 ± 3.57 vs. 5.52 ± 5.92; p < 0.01) was increased, while no correlation between GCF and blood was found (Spearman's rho: 0.175; p = 0.23). Furthermore, higher blood concentrations of MMP-8 and tissue inhibitor of MMP (TIMP-1) were detected in patients with increased periodontal inflammation (BOP positive, p < 0.01). CONCLUSION: Periodontal inflammation appears associated to MMP-8 and TIMP-1 in blood. Thereby, clinical interaction between periodontal conditions, periodontal pathogenic bacteria and RA-related cytokines remain unclear. | |
31699188 | [High Expression of Multidrug Resistance Gene-1 Can Aggravate Resistance to Methotrexate i | 2019 Oct 30 | Objective To explore the role of multidrug resistance gene-1(MDR1)gene in methotrexate(MTX)resistance in patients with rheumatoid arthritis(RA).Methods Fibroblast-like synoviocytes(FLS)from RA patients were infected with recombinant adenovirus Ad-EGFP-MDR1 in vitro to obtain MDR1 over-expressed RA FLS.The transcription level of MDR1 gene and the expression level of its coding product P-glycoprotein(P-gp) rotein were detected by real-time PCR and Western blot analysis.The efflux function was verified by rhodamine 123 efflux assay.The resistance to MTX was detected by MTT assay.Results RA FLS were infected with recombinant adenovirus Ad-EGFP-MDR1;72 hours later,the particles size in MDR1 over-expressed RA FLS increased,the cell volume became larger,and the growth rate decreased.The transcription level of MDR1(1.4325±0.3924 vs.0.0650±0.0070;t=6.035,P=0.004),the expression level of P-gp protein(1.8667±0.2857 vs. 0.9367±0.0551;t=5.536,P=0.005),and the ability of extracellular rhodamine 123(979.43±196.81 vs.1680.06±147.04;t=-4.940,P=0.008) in MDR1 over-expressed RA FLS were significantly higher than those of negative virus control RA-FLS,and the survival rate of MDR1 over-expressed RA FLS was significantly increased at each concentration of MTX(P<0.05).Conclusion The high expression of MDR1 can affect the efflux ability to MTX by up-regulating the expression of P-gp,thus enhancing the drug resistance to MTX in RA FLS. |