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ID PMID Title PublicationDate abstract
30271124 Patterns and predictors of long-term retention of inflammatory bowel or rheumatoid disease 2018 BACKGROUND: Long-term effectiveness is an important factor when considering treatment decisions. OBJECTIVE: To determine the long-term retention patterns of Canadian inflammatory bowel disease (IBD) and rheumatologic disease (RD) patients, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with innovator infliximab (IFX) and to assess the impact of year-over-year cumulative IFX exposure on retention in both patient populations. PATIENTS AND METHODS: This analysis used a Canadian longitudinal prescription claims database to measure retention on IFX over a period of 5 years. Twelve-month unadjusted odds ratios of retention by time on IFX were calculated for the overall cohort, and within-group comparisons evaluated differences according to age, sex, region, insurance coverage, use of concomitant immunosuppressant therapy, indication (RD cohort only), and previous biologic experience. Between-group analyses compared unadjusted 5-year retention among the same variables. Variables that were independently associated with longer retention on IFX were identified using multivariable regression. RESULTS: Seven thousand eight hundred and six IBD patients and 2,935 RD patients on stable treatment with IFX were included in the analysis. Sixty-nine percent of IBD patients and 66% of RD patients were retained on IFX after 1 year and 33% and 29%, respectively, were retained after 5 years. Moreover, the probability of being retained on IFX significantly increased with cumulative time on IFX. Independent predictors of 5-year retention included sex, region, and type of insurance coverage among IBD patients and region, type of insurance, prior biologic therapy, and specific indication among RD patients. Patients with IBD were 17% more likely to be retained on IFX over 5 years compared to patients with RD. CONCLUSION: Real-world Canadian IBD and RD patients on IFX have good overall long-term treatment retention. Previous duration of IFX treatment predicts better future retention, and this knowledge could help inform treatment decisions when patients have been stable on IFX treatment for varying periods of time.
29532268 Monoclonal gammopathy in rheumatic diseases. 2018 Jul To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P = 0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P = 0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P = 0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P = 0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015-1.251), P = 0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011-1.242), P = 0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551-197.435), P = 0.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed.
30555457 Staphylococcus aureus PSM Peptides Modulate Human Monocyte-Derived Dendritic Cells to Prim 2018 Staphylococcus aureus (Sa), as one of the major human pathogens, has very effective strategies to subvert the human immune system. Virulence of the emerging community-associated methicillin-resistant Sa (CA-MRSA) depends on the secretion of phenol-soluble modulin (PSM) peptide toxins e.g., by binding to and modulation of innate immune cells. Previously, by using mouse bone marrow-derived dendritic cells we demonstrated that PSMs in combination with various Toll-like receptor (TLR) ligands induce a tolerogenic DC phenotype (tDC) characterized by the production of IL-10 and impaired secretion of pro-inflammatory cytokines. Consequently, PSM-induced tDCs favored priming of CD4(+)CD25(+)FoxP3(+) T(regs) with suppressor function while impairing the Th1 response. However, the relevance of these findings for the human system remained elusive. Here, we analyzed the impact of PSMα3 on the maturation, cytokine production, antigen uptake, and T cell stimulatory capacity of human monocyte-derived DCs (moDCs) treated simultaneously with either LPS (TLR4 ligand) or Sa cell lysate (TLR2 ligand). Herein, we demonstrate that PSMs indeed modulate human moDCs upon treatment with TLR2/4 ligands via multiple mechanisms, such as transient pore formation, impaired DC maturation, inhibited pro- and anti-inflammatory cytokine secretion, as well as reduced antigen uptake. As a result, the adaptive immune response was altered shown by an increased differentiation of naïve and even CD4(+) T cells from patients with Th1/Th17-induced diseases (spondyloarthritis and rheumatoid arthritis) into CD4(+)CD127(-)CD25(hi)CD45RA(-)FoxP3(hi) regulatory T cells (T(regs)) with suppressor function. This T(reg) induction was mediated most predominantly by direct DC-T-cell interaction. Thus, PSMs from highly virulent Sa strains affect DC functions not only in the mouse, but also in the human system, thereby modulating the adaptive immune response and probably increasing the tolerance toward the bacteria. Moreover, PSMα3 might be a novel peptide for tolerogenic DC induction that may be used for DC vaccination strategies.
30200167 The efficacy of oral versus intravenous tranexamic acid in reducing blood loss after prima 2018 Sep BACKGROUND: Blood management after arthroplasties has become a serious problem. The objective is to perform a meta-analysis to compare the efficacy and safety between oral tranexamic acid (TXA) and intravenous TXA for blood management in total knee and hip arthroplasty. METHODS: We systematically searched randomized controlled trials (RCTs) from Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Google scholar. Eligibility criteria: Patients: adult patients with end-stage joint osteoarthritis, rheumatoid arthritis, and osteonecrosis of the femoral head, who prepared for TJA; Interventions: The experiential group received the intravenous form of TXA; Comparisons: Oral form of TXA; Outcomes: Total blood loss, hemoglobin reduction, transfusion requirements, duration of hospitalization, and thrombotic complications including deep vein thrombosis (DVT) and pulmonary embolism (PE); Study design: Randomized control trials (RCTs) and non-RCT. Meta-analysis results were collected and analyzed by the software STATA 11.0. After testing for heterogeneity between studies, data were aggregated for random-effects models when necessary. RESULTS: Four RCTs and 2 non-RCTs were included in the meta-analysis. The present meta-analysis revealed that there were no significant differences regarding total blood loss (WMD = -25.013, 95% CI: -51.002 to 0.977, P = .059), postoperative hemoglobin decline (WMD = -0.090, 95% CI: -0.205 to 0.024, P = .122), or transfusion rate (RD = -0.039, 95% CI: -0.080 to 0.002, P = .062) between the 2 groups. CONCLUSION: Oral TXA shows comparable efficacy to that of the intravenous forms after total knee and hip arthroplasty. Due to the limited quality of evidence currently available, higher quality RCTs is necessary.
29982686 Outcomes of Pregnancies With Maternal/Paternal Exposure in the Tofacitinib Safety Database 2018 Nov 29 BACKGROUND: Active inflammatory bowel disease increases the risk of adverse pregnancy outcomes. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). As a small molecule, tofacitinib is likely to cross the placental barrier; however, information on the effects of tofacitinib on pregnancy outcomes is limited. We report pregnancy and newborn outcomes among patients in UC clinical studies with prenatal (maternal/paternal) exposure to tofacitinib. METHODS: Pregnancies with maternal/paternal exposure to tofacitinib were identified and outcomes reported in 5 tofacitinib UC interventional studies (up to March 2017). Outcomes from tofacitinib rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis interventional studies, and RA noninterventional postapproval safety studies, spontaneous adverse event reporting, and registry data are also reported. RESULTS: Of 1157 patients enrolled in the UC interventional studies, 301 were women of childbearing age. Eleven cases of maternal exposure and 14 cases of paternal exposure to tofacitinib (doses of 5 mg or 10 mg twice daily) before/at the time of conception or during pregnancy were identified. Outcomes included 15 healthy newborns, no fetal deaths, no neonatal deaths, no congenital malformations, 2 spontaneous abortions, and 2 medical terminations. Outcomes across other tofacitinib studies and postmarketing cases were consistent, with a healthy newborn being the most common outcome and no fetal deaths. CONCLUSIONS: Based on the limited data available, pregnancy and newborn outcomes among patients with prenatal (maternal/paternal) exposure to tofacitinib in UC studies appear similar to those reported for other tofacitinib clinical study populations and the general population.
30411382 Systematic review: efficacy and safety of switching patients between reference and biosimi 2019 Jan BACKGROUND: Biosimilar versions of widely prescribed drugs, including the tumour-necrosis factor antagonist infliximab, are becoming increasingly available. As biosimilars are not identical copies of reference products, evidence may be required to demonstrate that switching between a reference biologic and biosimilars is safe and efficacious. To establish interchangeability, US Food and Drug Administration guidance states that studies must demonstrate that biosimilars remain equivalent or non-inferior to a reference product after multiple switches between products. AIMS: To investigate the evidence evaluating the safety and efficacy of switching between reference and biosimilar infliximab in patients with inflammatory disorders, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. METHODS: Published studies presenting data on switching between reference and biosimilar infliximab were identified by searching the MEDLINE database. Congress abstracts were identified by searching the EMBASE database and manually searching abstracts from relevant congresses. RESULTS: A total of 113 journal articles and 149 abstracts were found. Of these, 70 were considered relevant and included in this analysis. Most of the publications were uncontrolled, observational studies. Data from six randomised, controlled trials were identified. In general, the evidence revealed no clinically important efficacy or safety signals associated with switching. CONCLUSIONS: While available data have not identified significant risks associated with a single switch between reference and biosimilar infliximab, the studies available currently report on only single switches and were mostly observational studies lacking control arms. Additional data are needed to explore potential switching risks in various populations and scenarios.
30183456 Managing cancer risk in patients with systemic lupus erythematous. 2018 Oct INTRODUCTION: Numerous studies have clearly demonstrated that there is an altered cancer risk profile in patients with systemic lupus erythematous (SLE) versus the general population. This includes a higher risk of certain cancers (e.g. hematologic, lung) and a decreased risk of others (e.g. breast cancer). Several determinants could be behind this altered risk; these include immunosuppressant drugs, viral exposures, genetic factors, and other variables. Area covered: We review what is known regarding specific risk profiles and risk factors for some key cancers in SLE, including hematologic malignancies and lung cancers. In light of this, we examine current guidelines and practices regarding cancer screening, and propose ways that patients and physicians might help manage cancer risk in SLE. Expert commentary: Despite significant progress over the past decade, not many risk factors have been precisely identified. A better understanding of the elements that drive malignancy risk in systemic autoimmune rheumatic diseases may permit the further development of guidelines (regarding. cancer screening) for SLE patients. ABBREVIATIONS: AbTG: Anti-thyroglobulin antibodies; AbTPO: Anti-peroxydase antibodies; AML: Acute myeloid leukemia; APRIL: A proliferating-inducing ligand; BAFF: B-cell activating factor; CAPA: Canadian Arthritis Patient Alliance; CI: Confidence interval; CIN: Cervical intraepithelial neoplasia; CT: Computed tomography; DLBCL: Diffuse large B cell lymphoma; dsDNA: Double-stranded DNA; EBV: Epstein-Barr virus; EULAR European League Against Rheumatism; IBD: Inflammatory bowel disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HR: Hazard ratio; HSIL: High-grade cervical squamous intraepithelial lesions; HSV: Herpes simplex virus; HL: Hodgkin lymphoma; HPV: Human papillomavirus; MALT: Mucosa-associated lymphoid tissue; MDS: Myelodysplastic syndrome; MESNA: 2-mercaptoethane sodium sulfonate; NHL: Non-Hodgkin lymphoma; OR: Odds ratio; Pap: Papanicolaou; RA: Rheumatoid arthritis; SLE: Systemic Lupus erythematous; SLICC: Systemic International Collaborating Clinics; SNPs: Single-nucleotide polymorphisms; SOGC: Society of Obstetricians and Gynaecologists of Canada.
29618462 Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopat 2018 Apr 10 Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor-negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely.
29272750 Substrate-derived triazolo- and azapeptides as inhibitors of cathepsins K and S. 2018 Jan 20 Cathepsin (Cat) K is a critical bone-resorbing protease and is a relevant target for the treatment of osteoporosis and bone metastasis, while CatS is an attractive target for drugs in autoimmune diseases (e.g. rheumatoid arthritis), emphysema or neuropathic pain. Despite major achievements, current pharmacological inhibitors are still lacking in safety and may have damaging side effects. A promising strategy for developing safer reversible and competitive inhibitors as new lead compounds could be to insert non-cleavable bonds at the scissile P1-P1' position of selective substrates of CatS and CatK. Accordingly, we introduced a 1,4-disubstituted 1,2,3-triazole heterocycle that mimics most of the features of a trans-amide bond, or we incorporated a semicarbazide bond (azaGly residue) by replacing the α-carbon of the glycyl residue at P1 by a nitrogen atom. AzaGly-containing peptidomimetics inhibited powerfully their respective target proteases in the nM range, while triazolopeptides were weaker inhibitors (Ki in the μM range). The selectivity of the azaGly CatS inhibitor (1b) was confirmed by using spleen lysates from wild-type vs CatS-deficient mice. Alternatively, the azaGly bradykinin-derived CatK inhibitor (2b) potently inhibited CatK (Ki = 9 nM) and impaired its kininase activity in vitro. Molecular modeling studies support that the semicarbazide bond of 2b is more favorable than the 1,2,3-triazole linkage of the bradykinin-derived pseudopeptide 2a to preserve an effective affinity towards CatK, its protease target.
30170451 MMP-8 single-nucleotide polymorphisms are related to ankylosing spondylitis in Chinese Han 2018 Aug Ankylosing spondylitis (AS) is an extreme form of inflammatory arthritis which always leads to bony fusion of vertebral and chronic pain of back. A lot of genes including interleukin, matrix metalloproteinases (MMPs), and endoplasmic reticulum aminopeptidase were found associated with AS. MMP family members were involved in the autoimmune disease and orthopedic diseases such as rheumatoid arthritis and osteoarthritis, while few studies concentrated on the correlation between single-nucleotide polymorphisms (SNPs) in MMP and AS. In addition, there is no report on the relationship between MMP-8 and AS. To investigate the association between SNPs in MMP-8 and AS, we recruited 268 patients with AS and 654 healthy people to conduct a case-control study. Five SNPs including rs3740938, rs2012390, rs1940475, rs11225394, and rs11225395 of MMP-8 gene were genotyped. It was found rs3740938 of MMP-8 was associated with an increased risk of AS under the dominant model and additive model after adjustment for gender and age by performing logistic regression analysis (odds ratio [OR] = 1.49, 95% confidence interval [CI] = 1.02-2.18, P = .038; OR = 1.37, 95% CI = 1.01-1.87, P = .042, respectively). Moreover, haplotype "GGTCA" was associated with an increased risk of AS without adjustment for age and gender (OR = 1.75, 95% CI = 1.05-2.92, P = .032), while no positive result was found after adjustment for age and gender. Based on our results, our study indicates significant association between SNPs of MMP-8 and AS risk in a Chinese Han population and these results provide the first evidence that MMP-8 is correlated with AS.
29728446 TAS05567, a Novel Potent and Selective Spleen Tyrosine Kinase Inhibitor, Abrogates Immunog 2018 Jul Spleen tyrosine kinase (Syk) is involved in regulation of B-cell receptor (BCR) and Fc receptor downstream signal pathways. Syk plays an essential role in production of inflammatory mediators and differentiation in various immune cells and is therefore an attractive target for treating inflammatory conditions, such as autoimmune and allergic diseases. We identified TAS05567 as a highly selective Syk inhibitor and evaluated its therapeutic potential in animal models. In vitro biochemical assays were performed with available kinase assay panels. Inhibitory effects of TAS05567 on immune cells were analyzed by assessing the Syk downstream signaling pathway and production of inflammatory factors. In vivo effects of TAS05567 were evaluated in animal models of autoimmune diseases and antigen-specific IgE transgenic mice. TAS05567 inhibited only 4 of 191 kinases tested but inhibited Syk enzymatic activity with high potency. TAS05567 inhibited BCR-dependent signal transduction in Ramos cells, FcγR-mediated tumor necrosis factor-α production in THP-1 cells, and FcεR-mediated histamine release from RBL-2H3 cells. In rheumatoid arthritis models, TAS05567 suppressed hind-paw swelling in a dose-dependent manner compared with vehicle. Moreover, TAS05667 markedly reduced histopathologic scores in an established rat arthritis model. In a mouse immune thrombocytopenic purpura model, platelet counts were reduced with injection of anti-platelet antibody. TAS05567 prevented the platelet count decrease in a dose-dependent manner. Finally, TAS05567 treatment suppressed IgE-mediated ear swelling in vivo. Collectively, our data indicate TAS05567 is a selective Syk inhibitor and potential therapeutic candidate for treating humoral immune-mediated inflammatory conditions such as autoimmune and allergic diseases.
29731495 A Case of Sjögren's Syndrome Complicated with Interstitial Nephritis and Delayed Onset Au 2018 A 61-year-old woman was admitted to our hospital because of muscle paralysis and was found to have severe hypokalemia. A gallium-67 scintigram revealed a positive accumulation in the bilateral salivary glands, and a labial minor salivary gland biopsy demonstrated a massive lymphocyte infiltrate around the salivary ducts. She was diagnosed with Sjögren's syndrome (SS) associated with renal tubular acidosis. Renal biopsy revealed tubulointerstitial nephritis with a mild focal infiltration of lymphocytes and plasma cells. These pathological features were compatible with SS with renal involvement. Acidosis and hypokalemia were corrected with sodium bicarbonate and potassium chloride, which relieved the patient's symptoms. Although steroid therapy has been reported to be effective in SS-associated tubulointerstitial nephritis, the patient's serum potassium level could be controlled without administering steroids during the first admission. Five years later, she was admitted again because of severe liver dysfunction attributed to autoimmune hepatitis. Oral administration of prednisolone resulted in the normalization of her transaminase levels, and the control of her serum potassium level became easier. It has been reported that patients with SS with salivary gland involvement tend to have hepatic complications, and those with hepatic complications tend to have renal involvement. Physicians should be aware of hepatic involvement, even if there is no liver dysfunction at the initial diagnosis of SS with salivary gland and renal involvement. It remains uncertain whether the administration of a low dose of steroids before the onset of autoimmune hepatitis might have prevented the development of liver dysfunction in our patient.
29061446 Increased proportion of a CD38(high)IgD(+) B cell subset in peripheral blood is associated 2018 Feb We investigated the correlation between the increased proportion of peripheral B cell subsets and clinical and immunological features in primary Sjögren's syndrome (pSS). We found that the proportion of CD19(+) B cells was significantly increased in pSS as compared with HC and was correlated with serum IgG levels. Moreover, in vitro IgG production by CD19(+) B cells was significantly increased in pSS and was positively and significantly correlated with serum IgG levels. FACS analysis revealed that the proportions of peripherally CD38(high)IgD(+) B cells and CD38(high)IgD(-) B cells were significantly increased in pSS. In addition, the proportion of CD38(high)IgD(+) B cells positively correlated with ESSDAI scores and serum levels of IgG, anti-Ro/SSA and anti-La/SSB antibodies while that of CD38(high)IgD(-) B cells showed no correlation with these parameters. Our data suggest that increased proportion of CD38(high)IgD(+) B cells in pSS is involved in IgG overproduction including autoantibodies, and correlates with disease progression.
30042108 Corneal perforation in undiagnosed Sjögren's syndrome following topical NSAID and steroid 2018 Jul 24 A 74-year-old man presented with a progressive decrease in visual acuity and foreign body sensation in his right eye 8 days post uncomplicated phacoemulsification cataract surgery and intraocular lens insertion. The patient had been placed on a perioperative cataract regimen which consisted of G. Maxitrol (dexamethasone, polymyxin B sulfate, neomycin sulfate) four times a day and G. Yellox twice daily (bromfenac, a non-steroidal anti-inflammatory) for 2 weeks. On examination, he had a corneal ulcer and stromal thinning in his right eye which progressed to a full thickness perforation 12 hours later. The patient required a full thickness tectonic corneal transplant. Direct questioning revealed that this patient had both dry mouth and eyes. Serology revealed that the patient was positive for rheumatoid factor and for anti-Ro and anti-La antibodies. A parotid gland biopsy revealed significant lymphocytic infiltrate consistent with Sjögren's syndrome.
28573368 How common is depression in patients with polymyalgia rheumatica? 2018 Jun Depression is common in inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus and negatively impacts on outcomes. Given the long-term nature of polymyalgia rheumatica (PMR) and its glucocorticoid treatment, these patients may be at an increased risk of depression, although few studies exist to date. This study aimed to investigate the prevalence of, and factors associated with, depression in PMR patients. Prevalent PMR patients (with a first diagnostic code for PMR in the last 3 years) were mailed a postal questionnaire (n = 704) examining PMR symptoms, glucocorticoid use and patient reported comorbidities. Depressive symptoms were assessed using the Patient Health Questionnaire-8 (PHQ-8), with a score of ≥10 defined as current depressive symptoms. Logistic regression was used to examine association between demographics, comorbidity and current depressive symptoms. Five hundred fifty (78%) patients responded, of which 365 (66%) were female, with a mean (SD) age of 74.1 years (8.4). The prevalence of current depressive symptoms was 15% (n = 81) and was significantly associated with female gender: OR 1.87 (95%CI 1.08-3.22), current PMR symptoms: OR 2.1 (1.11-3.97), self-reported acid reflux: OR 1.75 (1.05-2.93) and diabetes: OR 2.86 (1.6-5.09). Older patients were less likely to report current depressive symptoms (OR 0.35 (0.13-0.9) for those >80 years versus those aged 50-59 years). Depressive symptoms are common in patients with PMR patients, especially younger patients and those with comorbidities. Clinicians should consider screening these patients for depressive symptoms and managing them appropriately, as untreated depression may negatively impact on health-related outcomes and quality of life.
30571714 A robust intracellular metabolite extraction protocol for human neutrophil metabolic profi 2018 Neutrophils are phagocytic innate immune cells that play essential roles in host defence, but are also implicated in inflammatory diseases such as rheumatoid arthritis (RA) where they contribute to systemic inflammation and joint damage. Transcriptomic analysis of neutrophils has revealed significant changes in gene expression in neutrophils activated in vitro by cytokines and in vivo during inflammation in RA. However, there are no reports on the global metabolomic changes that occur as a consequence of this activation. The aim of this study was to establish protocols for the study of changes in the metabolome of human neutrophils using 1H NMR spectroscopy. Sample preparation and spectral analysis protocols were optimised using neutrophils isolated by Ficoll-Paque, with decreased washing steps and inclusion of a heat-shock step to quench metabolite turnover. Cells were incubated ± PMA for 15 min in HEPES-free media and samples were analysed by NMR using a 700 MHz NMR Avance IIIHD Bruker NMR spectrometer equipped with a TCI cryoprobe. Chenomx, Bruker TopSpin and AMIX software were used to process spectra and identify metabolites. Principal Component Analysis (PCA) and signalling pathway analysis was carried out using Metaboanalyst. Cell number and number of scans (NS) were optimised as >3.6 million cells and 512 NS. 327 spectral bins were defined in the neutrophil spectra, of which 287 (87.7%) were assigned to 110 metabolites that included: amino acids, peptides and analogues; carbohydrates, carbonyls and alcohols; nucleotides, nucleosides and analogues; lipids and lipid-like molecules; benzenoids; and other organic compounds. 43 metabolites changed at least 1.5 fold (increase or decrease) after the addition of PMA for 5 or 15 min. Pathway analysis revealed that PMA affected nicotinate and nicotinamide metabolism, aminoacyl-tRNA biosynthesis and glycolysis, suggesting a redirection of glucose metabolism from glycolysis to the pentose phosphate pathway and production of NADPH for activation of the NADPH oxidase and subsequent respiratory burst. We have developed protocols for the study of human neutrophils by 1H NMR spectroscopy. Importantly, this methodology has sufficient sensitivity and reproducibility to detect changes in metabolite abundance from cell numbers typically collected from clinical samples or experiments with multiple assay conditions.
29602804 Response to comment on "Synovial fibroblast-neutrophil interactions promote pathogenic ada 2018 Mar 30 The citrullinome cargo in neutrophil extracellular traps varies according to disease condition and stimulation conditions.
29609207 Open-Label, Non-Mandatory Transitioning From Originator Etanercept to Biosimilar SB4: Six- 2018 Sep OBJECTIVE: To evaluate the effects of non-mandatory transitioning from the originator biologic drug etanercept (ETN) to its biosimilar, SB4, on drug survival and effectiveness in a controlled cohort study of patients with an inflammatory rheumatic disease. METHODS: In 2016, 642 patients were asked to transition their treatment from originator ETN to biosimilar SB4 by a structured communication strategy with opt-out option. Patients who consented to switch to SB4 were considered eligible for inclusion in the transition cohort, while patients being treated with originator ETN in 2014 were recruited as the historical cohort. Drug survival was compared between the 2 cohorts using Cox regression analyses, which were adjusted for age, sex, diagnosis, ETN treatment duration, ETN dose interval, conventional synthetic disease-modifying antirheumatic drug usage, and C-reactive protein (CRP) level, with a robust variance estimator applied to account for repeated subjects (i.e., patients who were included in both the transition cohort and the historical cohort). Adjusted differences in the 6-month change in CRP level, Disease Activity Score in 28 joints using CRP level (DAS28-CRP), and Bath Ankylosing Spondylitis Disease Activity Index were also assessed. RESULTS: Of the 642 ETN-treated patients, 635 (99%) agreed to transition from originator ETN to biosimilar SB4, of whom 625 patients (433 with rheumatoid arthritis, 128 with psoriatic arthritis, and 64 with ankylosing spondylitis) were included in the transition cohort, and 600 ETN-treated patients from 2014 were included in the historical cohort. The crude treatment persistence rate for biosimilar SB4 over 6 months was 90% (95% confidence interval [95% CI] 88-93%), compared to a 6-month treatment persistence rate of 92% (95% CI 90-94%) for originator ETN. Patients in the transition cohort, compared to the historical cohort, had a statistically significantly higher relative risk of treatment discontinuation (adjusted hazard ratio 1.57, 95% CI 1.05-2.36) and showed smaller decreases in the CRP level (adjusted difference 1.8, 95% CI 0.3-3.2) and DAS28-CRP (adjusted difference 0.15, 95% CI 0.05-0.25) over 6 months. CONCLUSION: Non-mandatory transitioning from originator ETN to biosimilar SB4 using a specifically designed communication strategy resulted in a slightly lower 6-month treatment persistence rate and smaller decreases in disease activity in the transition cohort compared to the historical cohort, but these differences were not considered clinically relevant.
29558353 [Cryoglobulins and cryoglobulinemic vasculitis]. 2018 Cryoglobulinemia is defined as the presence of cryoglobulins in the blood. Cryoglobulinemia is often observed in the course of many diseases (infection, hematological disorders, autoimmune disorders) or has an idiopathic character. The classification of cryoglobulinemia is based on the immunological analysis of cryoglobulins and the activity of the rheumatoid factor (RF). The presence of cryoglobulins may induce cryoglobulinemic vasculitis (CV) which manifests with skin changes, arthritis and the dysfunction of internal organs. Diagnosis of cryoglobulinemia refers to the detection of cryoprecipitate in the blood serum sample. In the treatment of cryoglobulinemia various groups of medications may be used: corticosteroids, cyclophosphamide, azathioprine and rituximab. The purpose of the treatment is to reduce the production of cryoglobulins and the inflammation caused by their presence. Additionally, the treatment of organs complication is also crucial. If the viral infection is the causative agent of vasculitis, combination therapy will be recommended: antiviral and immunosuppressive therapy.
30122288 Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis 2019 Jan 1 BACKGROUND: A relationship between non-neurological autoimmune (NNAI) disorders and psychosis has been widely reported but not yet subjected to meta-analysis. We conducted the first meta-analysis examining the association between NNAI disorders and psychosis and investigated the effect of 1) temporality (as determined by study design), 2) psychiatric diagnosis, and 3) specific autoimmune disorders. METHODS: Major databases were searched for articles published until April 2018; 31 studies, comprising data for >25 million individuals, were eligible. Using random-effects models, we examined the overall association between all NNAI disorders and psychosis; rheumatoid arthritis was examined separately given the well-established negative association with psychosis. Stratified analyses investigated the effect of temporality, psychiatric diagnosis, and specific NNAI disorders. RESULTS: We observed a positive overall association between NNAI disorders and psychosis (odds ratio [OR] = 1.26; 95% confidence interval [CI], 1.12-1.41) that was consistent across study designs and psychiatric diagnoses; however, considerable heterogeneity was detected (I(2) = 88.08). Patterns varied across individual NNAI disorders; associations were positive for pernicious anemia (OR = 1.91; 95% CI, 1.29-2.84), pemphigoid (OR = 1.90; 95% CI, 1.62-2.24), psoriasis (OR = 1.70; 95% CI, 1.51-1.91), celiac disease (OR = 1.53; 95% CI, 1.12-2.10), and Graves' disease (OR = 1.33; 95% CI, 1.03-1.72) and negative for ankylosing spondylitis (OR = 0.72; 95% CI, 0.54-0.98) and rheumatoid arthritis (OR = 0.65; 95% CI, 0.50-0.84). CONCLUSIONS: While we observed a positive overall association between NNAI disorders and psychosis, this was not consistent across all NNAI disorders. Specific factors, including distinct inflammatory pathways, genetic influences, autoantibodies targeting brain proteins, and exposure to corticosteroid treatment, may therefore underlie this association.