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ID PMID Title PublicationDate abstract
32421957 Upside and Downside of Tumor Necrosis Factor Blockers for Treatment of Immune/Inflammatory 2019 Tumor necrosis factor (TNF)-α, the most potent proinflammatory cytokine discovered to date, was first isolated in 1984 from human macrophage cells. Initially, it was thought to be a protein that was cytotoxic to tumor cells. But later, it was regarded as an agent that promotes inflammation and other chronic diseases found in humans. Currently, we know that the TNF superfamily (TNFS) has 19 members that perform a wide variety of functions via > 40 TNF receptors. Of TNFS members, TNF-α has been studied extensively and was found to be implicated in numerous autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, juvenile idiopathic arthritis, and diabetes. Thus, agents that can inhibit TNF-α have great potential for prevention and treatment of chronic diseases. To date, the U.S. Food and Drug Administration has approved many TNF-α blockers, such as etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab. These agents can block TNF-α actions and be used to treat different diseases. However, the uses of TNF-α blockers are not without serious adverse effects. Therefore, natural TNF-α blockers are best for developing safe, efficacious, and affordable agents for prevention and treatment of chronic diseases. The current review details the TNFS, functions of TNF-α in normal and disease conditions, roles of TNF-α blockers, and advantages and disadvantages.
31587140 Haploinsufficiency of A20 (HA20): updates on the genetics, phenotype, pathogenesis and tre 2020 Dec BACKGROUND: A20, a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3), plays a vital role in the negative regulation of inflammation and immunity. Loss-of-function mutation in TNFAIP3 leads to a new described autoinflammatory disease-haploinsufficiency of A20 (HA20). Since HA20 was first described in 2016, a number of new cases have been described in this literature, however, the disease and its pathogenesis are poorly understood. This review seeks to improve clinical recognition of this disorder, and promote both earlier diagnosis and initiation of targeted therapies to improve patients' outcomes. METHODS: We reviewed 26 papers about A20 and HA20, and we summarized genetic variants and clinical manifestations of a total of 61 reported patients from 26 families identified to have a genetic diagnosis of germline pathogenic variants in TNFAIP3/A20. Additionally, we discussed the pathogenesis and treatment of HA20. RESULTS: A total of 24 pathogenic variants of A20 had been reported. There was significant clinical heterogeneity, even among those with the same variants in TNFAIP3. Prior to receiving a molecular diagnosis of HA20, patients had been diagnosed with Behcet's disease, rheumatoid arthritis, rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, and even adult-onset Stills' disease. The patients with HA20 that presented with inflammatory signatures in NF-κB signaling were mostly responsive to treatment. CONCLUSIONS: HA20 is a monogenic autoinflammatory disease with highly variable clinical manifestations. This extensive heterogeneity makes it difficult to set a clinical diagnostic criteria, and genetic sequencing is necessary for a definitive diagnosis of HA20.
30965588 Biofunctional Nanofibrous Substrate for Local TNF-Capturing as a Strategy to Control Infla 2019 Apr 8 Rheumatoid arthritis (RA) is an autoimmune disease that affects the synovial cavity of joints, and its pathogenesis is associated with an increased expression of pro-inflammatory cytokines, namely tumour necrosis factor-alpha (TNF-α). It has been clinically shown to have an adequate response to systemic administration of TNF-α inhibitors, although with many shortcomings. To overcome such limitations, the immobilization of a TNF-α antibody on a nanofibrous substrate to promote a localized action is herein proposed. By using this approach, the antibody has its maximum therapeutic efficacy and a prolonged therapeutic benefit, avoiding the systemic side-effects associated with conventional biological agents' therapies. To technically achieve such a purpose, the surface of electrospun nanofibers is initially activated and functionalized, allowing TNF-α antibody immobilization at a maximum concentration of 6 µg/mL. Experimental results evidence that the biofunctionalized nanofibrous substrate is effective in achieving a sustained capture of soluble TNF-α over time. Moreover, cell biology assays demonstrate that this system has no deleterious effect over human articular chondrocytes metabolism and activity. Therefore, the developed TNF-capturing system may represent a potential therapeutic approach for the local management of severely affected joints.
31037575 Moringa rivae leaf extracts attenuate Complete Freund's adjuvant-induced arthritis in Wist 2020 Feb Moringa rivae is widely used as a traditional remedy against arthritis. The present research was designed to evaluate the anti-arthritic potential of Moringa rivae extracts. Treatment of rats with adjuvant-induced arthritis with methanolic and aqueous extracts of M. rivae (150, 300 or 600 mg/kg), and piroxicam (10 mg/kg) was started orally at day 8 post-administration of complete Freund's adjuvant and continued till 28th day. The therapeutic effect of the plant extracts was assessed in arthritic rats by arthritic index, body weight, and haematological and biochemical parameters. Furthermore, the modulatory effect on gene expression (I-κB, IL-4 and IL-10, COX-2, IL-1β and IL-6, NF-κB, and TNF-α) in the blood was determined using qRT-PCR, while ELISA assay was used to find PGE2 and TNF-α concentrations in the serum. Oxidative stress parameters in the liver and ankle joint histopathology were also evaluated. Moreover, the most effective methanolic extract was further characterized by GC-MS for the presence of phytochemicals. Treatment with the plant extracts significantly restored arthritic index, change in the body weight and immune organ weight, and the histopathological indices. Both extracts significantly (p < 0.05) reduced the serum concentration of rheumatoid factor, C-reactive protein, PGE2, and TNF-α in arthritic rats. The extracts persuasively down-regulated the COX-2, PGE2, IL-1β, IL-6, NF-κB, and TNF-α, and up-regulated the mRNA expression of I-κB, IL-4, and IL-10. Both extracts increased the activities of CAT and SOD while reducing the formation of MDA in a dose- dependent manner in the liver. Histopathological evaluation showed that treatment with the plant extracts significantly (p < 0.05) reduced joint inflammation, pannus formation, and bone erosion in treatment groups in comparison to arthritic control. Phytochemicals detected by GC-MS in the methanolic extract included esters, alcohols, ketones, fatty acids, and vitamin E. These findings provide evidence of the anti-arthritic potential of M. rivae extracts in chronic polyarthritis model.
31918528 Functional Outcomes After Critical Pathway for Inpatient Rehabilitation of Total Knee Arth 2019 Dec OBJECTIVE: To investigate functional outcomes after the application of a critical pathway for inpatient rehabilitation of total knee arthroplasty (TKA). METHODS: A total of 184 patients (57 males and 127 females; average age, 71.5±5.9 years) who underwent unilateral or bilateral TKA were included. The critical pathway included early, intensive individualized rehabilitation exercises. Patients completed the following performance-based physical function tests: the stair climbing test (SCT), 6-minute walk test (6MWT), and Timed Up and Go test (TUG) as well as measurement of isometric knee flexor and extensor strength of the operated knee, gait speed, and range of knee flexion and extension. Self-reported physical function and pain were measured using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS), respectively, and self-reported quality of life was measured using the EuroQoL 5 dimension (EQ-5D) questionnaire. These evaluations were performed preoperatively and at 1 month and 3 months postoperatively. RESULTS: Performance-based and self-reported physical function and quality of life measures improved nonlinearly over time. Specifically, the 6WMT, TUG, gait speed, WOMAC-pain, WOMAC-function, VAS, and EQ-5D scores showed a significant improvement at 1-month post-TKA, whereas SCT, peak torque of the knee extensors and flexors, and WOMAC-stiffness scores showed gradual, but substantial, improvements over 3 months. There were between-group differences (unilateral and bilateral TKA groups) in the time course of the SCT, 6MWT, TUG, VAS, WOAMC-stiffness, and WOMAC-function results. CONCLUSION: Patients who underwent critical pathway rehabilitation after TKA showed significant improvements in functional measurements during the first 3 months post-surgery.
31693847 Post-operative Physical Performance Factors Associated With Gait Speed in Patients Surgica 2019 Oct OBJECTIVE: To determine post-operative physical performance factors associated with gait speed in patients surgically treated for hip fracture. METHODS: Cross-sectional data from 59 patients (16 males and 43 females; mean age, 79.2±9.1 years) who underwent hip fracture surgery were enrolled. Patients completed a 10-meter walk test (10MWT) to assess gait speed. Additional physical performance tests included the Timed Up and Go test (TUG), the Berg Balance Scale (BBS), maximum voluntary isometric contraction (MVIC) of the knee extensors and flexors on the operated and non-operated sides as well as of the hip abductors (all tested using air-resistance weight machines), and analysis of spatio-temporal gait parameters at about 6 weeks after hip surgery. RESULTS: Bivariate analyses revealed a significant positive correlation between the post-operative 10MWT and the post-operative TUG, age, swing phase duration, and gait cycle duration along with a significant negative correlation between post-operative BBS score, MVIC of the knee extensors and flexors on the operated and non-operated sides, MVIC of the hip abductors, and cadence and stance phase duration. Linear regression analyses revealed that the post-operative TUG (β=0.85, p<0.01), gait cycle duration (β=0.17, p=0.02), and osteoporosis (β=-0.18, p=0.02) were associated with the post-operative 10MWT. CONCLUSION: The presence of osteoporosis, post-operative balance, and isometric muscle strength in the operated and non-operated legs were statistically associated with post-operative gait speed early after hip fracture surgery.
31279905 TLR9 signalling in HCV-associated atypical memory B cells triggers Th1 and rheumatoid fact 2019 Nov BACKGROUND & AIMS: Hepatitis C virus (HCV) infection contributes to the development of autoimmune disorders such as cryoglobulinaemia vasculitis (CV). However, it remains unclear why only some individuals with HCV develop HCV-associated CV (HCV-CV). HCV-CV is characterized by the expansion of anergic CD19(+)CD27(+)CD21(low/-) atypical memory B cells (AtMs). Herein, we report the mechanisms by which AtMs participate in HCV-associated autoimmunity. METHODS: The phenotype and function of peripheral AtMs were studied by multicolour flow cytometry and co-culture assays with effector T cells and regulatory T cells in 20 patients with HCV-CV, 10 chronicallyHCV-infected patients without CV and 8 healthy donors. We performed gene expression profile analysis of AtMs stimulated or not by TLR9. Immunoglobulin gene repertoire and antibody reactivity profiles of AtM-expressing IgM antibodies were analysed following single B cell FACS sorting and expression-cloning of monoclonal antibodies. RESULTS: The Tbet(+)CD11c(+)CD27(+)CD21(-) AtM population is expanded in patients with HCV-CV compared to HCV controls without CV. TLR9 activation of AtMs induces a specific transcriptional signature centred on TNFα overexpression, and an enhanced secretion of TNFα and rheumatoid factor-type IgMs in patients with HCV-CV. AtMs stimulated through TLR9 promote type 1 effector T cell activation and reduce the proliferation of CD4(+)CD25(hi)CD127(-/low)FoxP3(+) regulatory T cells. AtM expansions display intraclonal diversity with immunoglobulin features of antigen-driven maturation. AtM-derived IgM monoclonal antibodies do not react against ubiquitous autoantigens or HCV antigens including NS3 and E2 proteins. Rather, AtM-derived antibodies possess rheumatoid factor activity and target unique epitopes on the human IgG-Fc region. CONCLUSION: Our data strongly suggest a central role for TLR9 activation of AtMs in driving HCV-CV autoimmunity through rheumatoid factor production and type 1 T cell responses. LAY SUMMARY: B cells are best known for their capacity to produce antibodies, which often play a deleterious role in the development of autoimmune diseases. During chronic hepatitis C, self-reactive B cells proliferate and can be responsible for autoimmune symptoms (arthritis, purpura, neuropathy, renal disease) and/or lymphoma. Direct-acting antiviral therapy clears the hepatitis C virus and eliminates deleterious B cells.
31366320 LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic 2019 Jul 31 BACKGROUND: Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. RESULTS: A dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. CONCLUSIONS: Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.
30275259 Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatr 2019 Feb OBJECTIVE: To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases. METHODS: The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria. RESULTS: In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody-positive JIA. The other forms were gathered under the term "others." These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities. CONCLUSION: An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical term JIA. These preliminary criteria will be formally validated with a dedicated project.
31708446 Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4(+) T 2019 Dec 3 Accumulation of lactate in the tissue microenvironment is a feature of both inflammatory disease and cancer. Here, we assess the response of immune cells to lactate in the context of chronic inflammation. We report that lactate accumulation in the inflamed tissue contributes to the upregulation of the lactate transporter SLC5A12 by human CD4(+) T cells. SLC5A12-mediated lactate uptake into CD4(+) T cells induces a reshaping of their effector phenotype, resulting in increased IL17 production via nuclear PKM2/STAT3 and enhanced fatty acid synthesis. It also leads to CD4(+) T cell retention in the inflamed tissue as a consequence of reduced glycolysis and enhanced fatty acid synthesis. Furthermore, antibody-mediated blockade of SLC5A12 ameliorates the disease severity in a murine model of arthritis. Finally, we propose that lactate/SLC5A12-induced metabolic reprogramming is a distinctive feature of lymphoid synovitis in rheumatoid arthritis patients and a potential therapeutic target in chronic inflammatory disorders.
31416923 Predictive Utility of Cardiovascular Risk Prediction Algorithms in Inflammatory Rheumatic 2020 Jun 1 OBJECTIVE: We performed a systematic review of the literature to describe current knowledge of cardiovascular (CV) risk prediction algorithms in rheumatic diseases. METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane Central databases was performed. The search was restricted to original publications in English, had to include clinical CV events as study outcomes, assess the predictive properties of at least 1 CV risk prediction algorithm, and include patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), or psoriasis. By design, only cohort studies that followed participants for CV events were selected. RESULTS: Eleven of 146 identified manuscripts were included. Studies evaluated the predictive performance of the Framingham Risk Score, QRISK2, Systematic Coronary Risk Evaluation (SCORE), Reynolds Risk Score, American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), and the Italian Progetto CUORE score. Approaches to improve predictive performance of general risk algorithms in patients with RA included the use of multipliers, biomarkers, disease-specific variables, or a combination of these to modify or develop an algorithm. In both SLE and PsA patients, multipliers were applied to general risk algorithms. In studies of RA and SLE patients, efforts to include nontraditional risk factors, disease-related variables, multipliers, and biomarkers largely failed to substantially improve risk estimates. CONCLUSION: Our study confirmed that general risk algorithms mostly underestimate and at times overestimate CV risk in rheumatic patients. We did not find studies that evaluated models for psoriasis or AS, which further demonstrates a need for research in these populations.
30879204 Podocytic infolding glomerulopathy: two new cases with connective tissue disease and liter 2019 May Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity, and only 29 cases have been reported worldwide so far, characterized by microspheres or microtubular structures or both associated with podocytic infolding into the glomerular basement membrane (GBM) on electron microscopy. We present two new cases of PIG with connective tissue disease (CTD), one with primary Sjögren's syndrome and the other with systemic lupus erythematosus (SLE), and make a systemic review of the literature. In the entire 31 patients of PIG, 24 (77.42%) were women and seven (22.58%) were men, with an average age of 41.2 ± 15.2 (ranging from 14 to 79) years old. Almost two-thirds of patients (67.74%) were diagnosed with CTD, in which 76.19% were SLE. All patients presented with proteinuria and six (19.35%) patients were accompanied with hematuria. Serum creatinine was elevated in six (19.35%) patients. Pathological findings of all patients were consistent with PIG characteristics, and four patients with repeated renal biopsies further provided profound insights.
31109638 Racial/Ethnic variations in morbidity and mortality in Adult Onset Still's Disease: An ana 2019 Dec OBJECTIVES: Adult Onset Still's Disease (AOSD) is a rare autoinflammatory disorder. There is relatively little known about the impact of social determinants of health on its outcomes. Our goal is to describe the racial/ethnic variations, morbidity and mortality of AOSD hospitalized patients in the US. MATERIALS AND METHODS: Adult US hospitalized patients between 2009-13 from a nationwide inpatient sample (NIS) database with AOSD were identified using ICD-9 code 714.2. NIS is the largest all-payer US inpatient database with approximately 8 million hospitalizations yearly. Patients with other autoimmune diseases were excluded. We used descriptive statistics to summarize patient and hospital characteristics. We performed survey-weighted logistic regression models adjusting for confounders to study our primary outcome: in-hospital mortality. RESULTS: Between 2009-13, 5,820 AOSD patients were hospitalized with a mean age of 53.6 (SE-0.61) years. 3817 (65.6%) were female, 56% white and 3% Asian. Macrophage Activating Syndrome (1.7%), Disseminated Intravascular Coagulation (DIC-1.1%) and Thrombotic Thrombocytopenic Purpura (0.4%), respectively, complicated the hospital course. There were 154 inpatient deaths in study period (mortality 2.6%). Mean age of patients who died in hospital was higher (62.4 years ± 3.1) and 13.9% were Asians. Patients of Asian origin had significantly higher odds of in-hospital death compared to whites (aOR = 6.39, 95% CI 1.77-23.1, p = 0.005). Mortality was significantly higher for patients whose hospital course was complicated by DIC (aOR = 29.69, 95% CI 5.5-160.41, p = 0.006). CONCLUSIONS: In this national sample of patients hospitalized for AOSD, we found significant variations in In-hospital mortality.
30846988 Single Cell Based Phosphorylation Profiling Identifies Alterations in Toll-Like Receptor 7 2019 Primary Sjögren's syndrome (pSS) is associated with polymorphisms and mRNA expression profiles that are indicative of an exaggerated innate and type I IFN immune response. Excessive activation potential of signaling pathways may play a role in this profile, but the intracellular signaling profile of the disease is not well characterized. To gain insights into potentially dysfunctional intracellular signaling profiles of pSS patients we conducted an exploratory analysis of MAPK/ERK and JAK/STAT signaling networks in peripheral blood mononuclear cells (PBMC) from 25 female pSS patients and 25 female age-matched healthy donors using phospho-specific flow cytometry. We analyzed unstimulated samples, as well as samples during a 4 h time period following activation of Toll-like receptor (TLR) 7 and 9. Expression levels of MxA, IFI44, OAS1, GBP1, and GBP2 in PBMC were analyzed by real-time PCR. Cytokine levels in plasma were determined using a 25-plex Luminex-assay. Principal component analysis (PCA) showed that basal phosphorylation profiles could be used to differentiate pSS patients from healthy donor samples by stronger intracellular signaling pathway activation in NK and T cells relative to B cells. Stimulation of PBMC with TLR7 and -9 ligands showed significant differences in the phosphorylation profiles between samples from pSS patients and healthy donors. Including clinical parameters such as extraglandular manifestations (EGM), we observed stronger responses of NF-κB and STAT3 S727 in B cells from EGM-negative patients compared to EGM-positive patients and healthy controls. Plasma cytokine levels were correlated to the basal phosphorylation levels in these patients. In addition, 70% of the patients had a positive IFN score. These patients differed from the IFN score negative patients regarding their phosphorylation profiles and their plasma cytokine levels. In conclusion, we here report increased signaling potentials in peripheral B cells of pSS patients in response to TLR7 and -9 stimulation through STAT3 S727 and NF-κB that correlate with a type I IFN signature. Induction of these pathways could contribute to the generation of a type I IFN signature in pSS. Patients displaying elevated potentiation of STAT3 S727 and NF-κB signaling could therefore benefit from therapies targeting these pathways.
31406382 Placental growth factor regulates the generation of T(H)17 cells to link angiogenesis with 2019 Oct Helper T cells actively communicate with adjacent cells by secreting soluble mediators, yet crosstalk between helper T cells and endothelial cells remains poorly understood. Here we found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the T(H)17 subset of helper T cells and promoted angiogenesis. Interestingly, the 'angio-lymphokine' PlGF, in turn, specifically induced the differentiation of pathogenic T(H)17 cells by activating the transcription factor STAT3 via binding to its receptors and replaced the activity of interleukin-6 in the production of interleukin-17, whereas it suppressed the generation of regulatory T cells. Moreover, T cell-derived PlGF was required for the progression of autoimmune diseases associated with T(H)17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, T(H)17 cell development and autoimmunity.
31747429 Overactive bladder and bladder pain syndrome/interstitial cystitis in primary Sjögren's s 2019 To investigate the risks of overactive bladder (OAB) and bladder pain syndrome/interstitial cystitis (BPS/IC) in primary Sjögren's syndrome (pSS) patients. A nationwide, population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. From 2001 to 2010, participants with newly diagnosed pSS were recognized as the study group. In addition, a comparison cohort of non-pSS participants was matched for age, gender, and initial diagnosis date. Risks of developing OAB and BPS/IC in pSS patients of different age, sex, and various therapeutic strategies were calculated. Hazard ratios (HR) and a 95% confidence interval (CI) were analyzed by Cox proportional hazard model. In total, 11,526 pSS patients were recognized. The HRs of OAB and BPS/IC in pSS patients were 1.68 (95% C.I.: 1.48-1.91, p<0.01) and 2.34 (95% C.I.: 1.59-3.44, p<0.01), respectively. The risks of OAB and BPS/IC were significantly increased for pSS patients aged < 65 years (HR: 1.73 and 2.67), female patients (HR: 1.74 and 2.34), and patients requiring treatment for dry eyes and dry mouth (HR: 2.06 and 2.93). pSS patients exhibited an increased risk of OAB and BPS/IC. Female gender, younger age, and severe glandular dysfunction requiring treatments were potential risk factors.
31686632 Hyperferritinaemia: An Iron Sword of Autoimmunity. 2019 BACKGROUND: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. METHODS: Different electronic databases were searched in a non-systematic way to find out the literature of interest. RESULTS: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still's diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. CONCLUSION: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.
31598752 Tocilizumab-induced anaphylaxis in patients with adult-onset Still's disease and systemic 2020 May The benefits afforded by tocilizumab (TCZ) in patients with adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) have been described in previous studies. However, few reports have evaluated severe hypersensitivity reactions (HSRs) to TCZ in patients with AOSD or SJIA. We describe three instances of TCZ-induced anaphylactic reactions in AOSD/SJIA patients, and review relevant prior reports on patients with various rheumatic diseases. Two of our cases exhibited shock and cardiovascular collapse; TCZ was discontinued in all three cases. All events occurred within 20 min of TCZ infusion, after at least three prior infusions, indicating an IgE-mediated mechanism and previous sensitization to TCZ. In all three cases, mild HSRs had been observed about 1 month before the anaphylactic events, but pre-medication with antihistamines and corticosteroids failed to prevent anaphylaxis. All three cases had active AOSD or SJIA disease, and were refractory to other immunosuppressive agents. It is essential to be aware that severe anaphylaxis to TCZ can develop in patients with active refractory AOSD or SJIA, and to be cautious when medicating certain patients. Anaphylaxis is a serious condition that can be fatal; TCZ infusion should not be re-challenged via pre-medication in patients who exhibited mild HSRs before TCZ without desensitization.
31433302 Sustained virological response from interferon-based hepatitis C regimens is associated wi 2019 Dec BACKGROUND & AIMS: HCV infection is associated with several extrahepatic manifestations (EHMs). We evaluated the impact of sustained virological response (SVR) on the risk of 7 EHMs that contribute to the burden of extrahepatic disease: type 2 diabetes mellitus, chronic kidney disease or end-stage renal disease, stroke, ischemic heart disease, major adverse cardiac events, mood and anxiety disorders, and rheumatoid arthritis. METHODS: A longitudinal cohort study was conducted using data from the British Columbia Hepatitis Testers Cohort, which included ~1.3 million individuals screened for HCV. We identified all HCV-infected individuals who were treated with interferon-based therapies between 1999 and 2014. SVR was defined as a negative HCV RNA test ≥24 weeks post-treatment or after end-of-treatment, if unavailable. We computed adjusted subdistribution hazard ratios (asHR) for the effect of SVR on each EHM using competing risk proportional hazard models. Subgroup analyses by birth cohort, sex, injection drug exposure and genotype were also performed. RESULTS: Overall, 10,264 HCV-infected individuals were treated with interferon, of whom 6,023 (59%) achieved SVR. Compared to those that failed treatment, EHM risk was significantly reduced among patients with SVR for type 2 diabetes mellitus (asHR 0.65; 95%CI 0.55-0.77), chronic kidney disease or end-stage renal disease (asHR 0.53; 95% CI 0.43-0.65), ischemic or hemorrhagic stroke (asHR 0.73; 95%CI 0.49-1.09), and mood and anxiety disorders (asHR 0.82; 95%CI 0.71-0.95), but not for ischemic heart disease (asHR 1.23; 95%CI 1.03-1.47), major adverse cardiac events (asHR 0.93; 95%CI 0.79-1.11) or rheumatoid arthritis (asHR 1.09; 95% CI 0.73-1.64). CONCLUSIONS: SVR was associated with a reduction in the risk of several EHMs. Increased uptake of antiviral therapy may reduce the growing burden of EHMs in this population. LAY SUMMARY: We estimated the rates of chronic comorbidities other than liver disease between those who were cured and those who failed treatment for hepatitis C virus (HCV) infection. Our findings showed that the rates of these non-liver diseases were largely reduced for those who were cured with interferon-based treatments. Early HCV treatments could provide many benefits in the prevention of various HCV complications beyond liver disease.
31416922 Evaluation of the Economic Burden of Psoriatic Arthritis and the Relationship Between Func 2020 May 1 OBJECTIVE: This analysis aimed to evaluate the economic burden of patients with psoriatic arthritis (PsA) on the UK healthcare system and estimate the relationship between functional status and direct healthcare costs. METHODS: Functional status [measured using the Health Assessment Questionnaire-Disability Index (HAQ-DI)], demographics, disease history, and healthcare resource use data were extracted from a cohort of patients at the Royal National Hospital for Rheumatic Diseases, Bath, UK. Each resource use item per patient was then allocated a unit cost. Linear regression models were used to predict costs as a function of HAQ-DI. Medication costs were not included in the primary analysis, which was carried out from the UK National Health Service perspective. RESULTS: Data were available for 101 patients. Mean HAQ-DI score was 0.84 (SD 0.75) and mean age at HAQ-DI measurement was 57.8 (SD 10.7). Total annual healthcare costs per patient, excluding medication costs, ranged between £174 and £8854, with a mean of £1586 (SD £1639). A 1-point increase in HAQ-DI score was associated with an increase in total costs of £547.49 (standard error £224), with secondary care consultations appearing to be the primary factor. Subgroup analyses suggested higher cost increases in patients with HAQ-DI scores of 2-3 and with a disease duration > 10 years. CONCLUSION: Patients with PsA place a significant economic burden on the healthcare system. Functional status is highly correlated with costs and appears to be driven mainly by the cost of secondary care consultations. Results were similar to previous studies in rheumatoid arthritis populations.