Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33440965 The prevalence of bipolar disorder in autoimmune disease: a systematic review and meta-ana 2021 Jan BACKGROUND: At the end of the last century, genome-wide association studies revealed a significant genetic association between bipolar disorder and autoimmune diseases. Subsequently, the theory of immune pathogenesis of bipolar disorder gradually formed, and the research on autoimmune diseases and bipolar comorbidities began to extend to other diseases, but their correlation is still controversial. To explore the differences in the prevalence of bipolar disorder in patients with autoimmune disease and normal healthy people through meta-analysis, and to examine the relationship between bipolar disorder and autoimmune disease by reviewing the relevant literature. METHODS: The Cochrane, PubMed, and Embase databases were searched by computer from the date of inception of the database to July 2020. The main topics of the search were based on common autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, pemphigus, and Sjogren's syndrome. The databases were comprehensively searched for controlled studies regarding the prevalence of bipolar disorder in patients with autoimmune diseases. Review Manager 5.3 software was used for meta-analysis. RESULTS: In total, 10 cohort and case control studies were included. From these, 16 control groups were extracted based on nine autoimmune diseases. The meta-analysis demonstrated that the incidence of bipolar disorder was significantly increased in patients with autoimmune disease compared to patients without autoimmune disease, [mean difference (MD) =1.54, 95% confidence interval (CI): 1.28-1.86, P<0.00001]. Also, in the meta-analysis based on five cross-sectional analyses (in which a total of five control groups were extracted based on five autoimmune diseases), the high comorbidity rate of autoimmune diseases and bipolar disorder was verified (MD =2.23, 95% CI: 1.62-3.07, P<0.00001). CONCLUSIONS: The prevalence of bipolar disorder is markedly higher in patients with autoimmune disease. Yet, more basic research is needed to verify the special significance of immune mechanisms in bipolar disorder.
33401396 The Role of Non-Selective TNF Inhibitors in Demyelinating Events. 2021 Jan 1 The use of non-selective tumor necrosis factor (TNF) inhibitors is well known in the treatment of inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis. Its use in neurological disorders is limited however, due to rare adverse events of demyelination, even in patients without preceding demyelinating disease. We review here the molecular and cellular aspects of this neuroinflammatory process in light of a case of severe monophasic demyelination caused by treatment with infliximab. Focusing on the role of TNF, we review the links between CNS inflammation, demyelination, and neurodegenerative changes leading to permanent neurological deficits in a young woman, and we discuss the growing evidence for selective soluble TNF inhibitors as a new treatment approach in inflammatory and neurological diseases.
32049579 Psychosocial Factors Associated with Sleep Quality and Duration Among Older Adults with Ch 2021 Feb Sleep complaints are common among older adults with chronic pain. Because of the risk of significant side effects, sleep medications are not recommended as first-line treatments. Little is known about the association between positive psychosocial factors and sleep, but further awareness could support non-drug strategies to minimize poor sleep. The purpose of this study was to (1) determine the prevalence of self-reported poor sleep quality and short/long sleep duration in a population of older adults with chronic pain, and (2) examine the associations of negative risk factors, sleep-inducing medications, and positive psychosocial characteristics on sleep outcomes in this population. This study analyzed survey responses from 4201 adults ages ≥65 years with diagnosed back pain, osteoarthritis, and/or rheumatoid arthritis, and at least 1 year of continuous medical and drug plan enrollment. The most commonly reported sleep outcome was short sleep duration (39%), followed by poor sleep quality (22%), and long sleep duration (9%). Based on pharmaceutical claims, prescriptions for opioids (59%) or benzodiazepines (22%) were common. Perceived stress, depression, and pain or sleep prescription medications were independently associated with poor sleep quality and short or long sleep durations. The positive psychosocial factors of higher resilience and more diverse social networks were independently associated with good sleep quality and optimal sleep duration. These results underscore the importance of social and coping factors to sleep, which may provide new opportunities to improve sleep and well-being in older adults with chronic pain.
33247992 Nocardiosis in a patient with pemphigus foliaceus treated with rituximab. 2021 Jan Rituximab is a chimeric human/murine monoclonal anti-CD20 antibody. This agent is an effective therapeutic option in severe types of pemphigus. However, rituximab may cause opportunistic infections if used in immunosuppressed patients. We reported a case of diffuse Nocardia infection following rituximab treatment in pemphigus foliaceus. Rheumatoid arthritis protocol applied in our patient. Rituximab was used at a dose of 1000 mg every 2 weeks. Because the disease was not adequately controlled, rituximab treatment was administered six times every 15 days. One week after the sixth dose of the rituximab, she presented lassitude and multiple palpable masses in soft tissue of the upper extremity. Thereafter, the aspirate culture of the abscess on the left shoulder was taken and confirmed to be disseminated nocardiosis. She was treated with linezolid and meropenem for 1 month; however, amikacin was added because the patient did not respond adequately to linezolid and meropenem therapy. The patient died of cardiac arrest because of her comorbidities. In this case, prolonged administration of rituximab therapy may have caused the development of nocardiosis. Therefore, all patients should have a sensible balance of risk and benefit, considering the use of rituximab.
33245272 The Dramatic Role of IFN Family in Aberrant Inflammatory Osteolysis. 2021 Skeletal system has been considered a highly dynamic system, in which bone-forming osteoblasts and bone-resorbing osteoclasts go through a continuous remodeling cycle to maintain homeostasis of bone matrix. It has been well acknowledged that interferons (IFNs), acting as a subgroup of cytokines, not only have crucial effects on regulating immunology but also could modulate the dynamic balance of bone matrix. In the light of different isoforms, IFNs have been divided into three major categories in terms of amino acid sequences, recognition of specific receptors and biological activities. Currently, type I IFNs consist of a multi-gene family with several subtypes, of which IFN-α exerts pro-osteoblastogenic effects to activate osteoblast differentiation and inhibits osteoclast fusion to maintain bone matrix integrity. Meanwhile, IFN-β suppresses osteoblast-mediated bone remodeling as well as exhibits inhibitory effects on osteoclast differentiation to attenuate bone resorption. Type II IFN constitutes the only type, IFN-γ, which exerts regulatory effects on osteoclastic bone resorption and osteoblastic bone formation by biphasic ways. Interestingly, type III IFNs are regarded as new members of IFN family composed of four members, including IFN-λ1 (IL-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) and IFN-λ4, which have been certified to participate in bone destruction. However, the direct regulatory mechanisms underlying how type III IFNs modulate the metabolic balance of bone matrix, remains poorly elucidated. In this review, we have summarized functions of IFN family during physiological and pathological conditions and described the mechanisms by which IFNs maintain bone matrix homeostasis via affecting the osteoclast-osteoblast crosstalk. In addition, the potential therapeutic effects of IFNs on inflammatory bone destruction diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and infectious bone diseases are also well displayed, which are based on the predominant role of IFNs in modulating the dynamic equilibrium of bone matrix.
34940835 T helper cells expressing fractalkine receptor and bearing T follicular helper 1-like cell 2021 Dec 23 OBJECTIVE: Since the pathological features of IgG4-related disease (IgG4-RD) include lymphocyte infiltration and fibrotic changes in the lesions, we investigated the significance of fractalkine (CX3CL1) and lymphocyte subsets in patients with IgG4-RD. METHODS: Peripheral blood and biopsied samples were obtained from healthy controls (HCs, n = 10), rheumatoid arthritis (RA, n = 10), and IgG4-RD patients (n = 16) and were analyzed by flow cytometry, immunohistology and costimulation assays. RESULTS: Peripheral CX3CR1+ CD4+ T cells had an approximately threefold increase in the IgG4-RD patients (15.4%), compared with the HCs (5.0%). In addition, CX3CR1+ CD4+ T cells were localized in the salivary glands of the IgG4-RD patients but not in those with Sicca syndrome. CX3CR1 was induced on 20% of CD4+ T cells after T cell receptor (TCR) simulation with IL-12 for five days-culture. CX3CR1+ T cells showed high expression of both CXCR5 and CXCR3. Moreover, they co-expressed Bcl-6 and T-bet, the master transcription factors for T helper 1 (Th1) and T follicular helper (Tfh) cells. After secondary stimulation, CX3CR1+ T cells produced both interferon-gamma (IFN-γ) and IL-21. Compared with their CX3CR1- counterparts, CX3CR1+ CD4+ T cells induced plasmablast differentiation from naïve B cells more efficiently (15.0 vs 5.0%) and increased the production of IgG2, IgG3, and IgG4 by B cells. CONCLUSION: CX3CR1+ CD4+ T cells characteristically increased in the peripheral blood and the affected tissues and were associated with an increase in the serum IgG4 levels of patients with IgG4-RD. This CD4 subset has a Th1/Tfh-like phenotype and a B cell helper function.
34886062 Mortality in Inflammatory Rheumatic Diseases: Lithuanian National Registry Data and System 2021 Nov 24 Despite significant improvement in survival, rheumatic diseases (RD) are associated with premature mortality rates comparable to cardiovascular and neoplastic disorders. The aim of our study was to assess mortality, causes of death, and life expectancy in an inflammatory RD retrospective cohort and compare those with the general population as well as with the results of previously published studies in a systematic literature review. Patients with the first-time diagnosis of inflammatory RD during 2012-2019 were identified and cross-checked for their vital status and the date of death. Sex- and age-standardized mortality ratios (SMR) as well as life expectancy for patients with inflammatory RDs were calculated. The results of a systematic literature review were included in meta-standardized mortality ratio calculations. 11,636 patients with newly diagnosed RD were identified. During a total of 43,064.34 person-years of follow-up, 950 death cases occurred. The prevailing causes of death for the total cohort were cardiovascular diseases and neoplasms. The age- and sex-adjusted SMR for the total cohort was calculated to be 1.32 (1.23; 1.40). Patients with rheumatoid arthritis if diagnosed at age 18-19 tend to live for 1.63 years less than the general population, patients with spondyloarthritis-for 2.7 years less, patients with connective tissue diseases-for almost nine years less than the general population. The findings of our study support the hypothesis that patients with RD have a higher risk of mortality and lower life expectancy than the general population.
34882360 The phytochemical plumbagin reciprocally modulates osteoblasts and osteoclasts. 2022 Jan 27 Bone metabolism is essential for maintaining bone mineral density and bone strength through a balance between bone formation and bone resorption. Bone formation is associated with osteoblast activity whereas bone resorption is linked to osteoclast differentiation. Osteoblast progenitors give rise to the formation of mature osteoblasts whereas monocytes are the precursors for multi-nucleated osteoclasts. Chronic inflammation, auto-inflammation, hormonal changes or adiposity have the potential to disturb the balance between bone formation and bone loss. Several plant-derived components are described to modulate bone metabolism and alleviate osteoporosis by enhancing bone formation and inhibiting bone resorption. The plant-derived naphthoquinone plumbagin is a bioactive compound that can be isolated from the roots of the Plumbago genus. It has been used as traditional medicine for treating infectious diseases, rheumatoid arthritis and dermatological diseases. Reportedly, plumbagin exerts its biological activities primarily through induction of reactive oxygen species and triggers osteoblast-mediated bone formation. It is plausible that plumbagin's reciprocal actions - inhibiting or inducing death in osteoclasts but promoting survival or growth of osteoblasts - are a function of the synergy with bone-metabolizing hormones calcitonin, Parathormone and vitamin D. Herein, we develop a framework for plausible molecular modus operandi of plumbagin in bone metabolism.
34852982 Combining current knowledge on DNA methylation-based age estimation towards the developmen 2022 Mar The estimation of chronological age from biological fluids has been an important quest for forensic scientists worldwide, with recent approaches exploiting the variability of DNA methylation patterns with age in order to develop the next generation of forensic 'DNA intelligence' tools for this application. Drawing from the conclusions of previous work utilising massively parallel sequencing (MPS) for this analysis, this work introduces a DNA methylation-based age estimation method for blood that exhibits the best combination of prediction accuracy and sensitivity reported to date. Statistical evaluation of markers from 51 studies using microarray data from over 4000 individuals, followed by validation using in-house generated MPS data, revealed a final set of 11 markers with the greatest potential for accurate age estimation from minimal DNA material. Utilising an algorithm based on support vector machines, the proposed model achieved an average error (MAE) of 3.3 years, with this level of accuracy retained down to 5 ng of starting DNA input (~ 1 ng PCR input). The accuracy of the model was retained (MAE = 3.8 years) in a separate test set of 88 samples of Spanish origin, while predictions for donors of greater forensic interest (< 55 years of age) displayed even higher accuracy (MAE = 2.6 years). Finally, no sex-related bias was observed for this model, while there were also no signs of variation observed between control and disease-associated populations for schizophrenia, rheumatoid arthritis, frontal temporal dementia and progressive supranuclear palsy in microarray data relating to the 11 markers.
34820151 miR-99a regulates CD4(+) T cell differentiation and attenuates experimental autoimmune en 2021 Dec 3 Multiple microRNAs exhibit diverse functions to regulate inflammatory and autoimmune diseases. MicroRNA-99a (miR-99a) has been shown to be involved in adipose tissue inflammation and to be downregulated in the inflammatory lesions of autoimmune diseases rheumatoid arthritis and systemic lupus erythematosus. In this study, we found that miR-99a was downregulated in CD4(+) T cells from experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis. Overexpression of miR-99a alleviated EAE development by promoting regulator T cells and inhibiting T helper type 1 (Th1) cell differentiation. Bioinformatics and functional analyses further revealed that the anti-inflammatory effects of miR-99a was attributable to its role in negatively regulating glycolysis reprogramming of CD4(+) T cells by targeting the mTOR pathway. Additionally, miR-99a expression was induced by transforming growth factor β (TGF-β) to regulate CD4(+) T cell glycolysis and differentiation. Taken together, our results characterize a pivotal role of miR-99a in regulating CD4(+) T cell differentiation and glycolysis reprogramming during EAE development, which may indicate that miR-99a is a promising therapeutic target for the amelioration of multiple sclerosis and possibly other autoimmune diseases.
34760002 Outcome of COVID-19 infection in multiple sclerosis patients receiving disease-modifying t 2021 BACKGROUND: With the spread of COVID-19, treatment of diseases such as multiple sclerosis (MS) should be resumed with caution due to the disease-modifying therapies (DMTs) used in this subset of patients and the immunoregulatory effects of these drugs. We aim to assess the outcome of COVID-19 infection in MS patients receiving DMTs. MATERIALS AND METHODS: This is a cross-sectional study involving 45 COVID-19-infected patients previously diagnosed with MS. The data regarding their MS status and the type of DMT taken by the patients were extracted from the Isfahan MS Institute registry and were summarized. Diagnosis of MS was based on the 2017 McDonald Criteria, and the diagnosis of COVID-19 was based on computed tomography scan and polymerase chain reaction of nasopharyngeal swabs. RESULTS: Out of the 45 MS patients infected with COVID-19, 5 had unfavorable outcomes. Two patients deceased and the other three had persistent respiratory complications on the 4-week follow-up visit. Hypertension, diabetes, seizures, and rheumatoid arthritis were among the comorbidities that the patients reported. Both patients who died received rituximab as part of their MS treatment. All other patients recovered completely. CONCLUSION: Each different drug category may possess a distinct risk for infection, therefore until robust evidence are available, the safest drug should be utilized or the therapy should be postponed, if possible, to minimize patient risk. Disease-modifying therapy use in MS patients should be cautiously applied as their effect on COVID-19 infection prognosis is not yet studied.
34759420 A Study of Cutaneous Adverse Drug Reactions and their Association with Autoimmune Diseases 2021 Jul BACKGROUND: Cutaneous adverse drug reactions (CADRs) comprise about 30% of all adverse drug reactions and observed in 2-3% of hospitalized patients by wide variety of offending agents. AIMS: To study the clinical patterns, causative drugs and their association with autoimmune diseases in CADR patients. MATERIALS AND METHODS: A total of 174 CADR patients who presented to the dermatology OPD over a period of 18 months (1 July 2015 to 31 Dec 2016) were considered for the study. Detailed history, clinical examination, hematological, and biochemical investigations were recorded. The venereal disease research laboratory test, HIV (ELISA), and histopathological examination were done wherever indicated. RESULTS: The mean age of the patients with cutaneous drug eruptions was 40.2 years. Most of them (31.0%) were in the age group of 41-50 years. There were 93 (53.4%) males and 81 (46.5%) females with the M:F ratio of 1.5:1. The most common eruption observed was maculopapular rash in 33.3% followed by fixed drug eruption (17.2%) and lichenoid dermatitis' (11.5%). The drugs most commonly responsible for CADRs were antimicrobials (n = 68, 39%) with fixed dose combination of fluoroquinolones with nitroimidazoles (n = 42). We also noticed that a total of 42 patients out of 174 had comorbities in the form of diabetes (n = 27, 15.5%), hypothyroidism (n = 9, 5.1%), rheumatoid arthritis (n = 3, 1.7%), vitiligo (n = 2, 1.1%), and SLE (n = 1, 0.5%). CONCLUSION: Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be because of the introduction of newer molecules and changing trends in the use of drugs. In our study, a significant relation of CADRs with autoimmune diseases (P value = 0.004) was also observed.
34689057 Emerging roles for IL-11 in inflammatory diseases. 2022 Jan Interleukin-11 (IL-11) is a cytokine that has been strongly implicated in the pathogenesis of fibrotic diseases and solid malignancies. Elevated IL-11 expression is also associated with several non-malignant inflammatory diseases where its function remains less well-characterized. Here, we summarize current literature surrounding the contribution of IL-11 to the pathogenesis of autoimmune inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, diabetes and systemic sclerosis, as well as other chronic inflammatory conditions such as periodontitis, asthma, chronic obstructive pulmonary disease, psoriasis and colitis.
34552181 Assessment of pancreatitis associated with tocilizumab use using the United States Food an 2021 Sep 22 Tocilizumab (TCZ) is used to treat rheumatoid arthritis and other systemic inflammatory disorders. There is some evidence suggesting the occurrence of pancreatitis following TCZ use. We aimed to determine the reporting of pancreatitis following TCZ use in comparison with other drugs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted adverse event reports submitted to FAERS during 2013-2019. A reporting odds ratio (ROR) with the lower bound 95% confidence interval (CI) > 1 and a lower limit of a two-sided 95% interval of information component (IC(025)) more than zero was considered significant. Following deduplication, 3,383,910 adverse event reports were available; 144 (0.004%) reports were of pancreatic adverse events associated with TCZ use, and 15,907 (0.47%) associated with other drugs. Of the 144 cases, 74 (51.39%) received concomitant medications with pancreatotoxic potential. The likelihood of reporting of pancreatic events, compared with any other adverse event, with TCZ use was 1.32 times higher than that with other drugs. The lower bound of the 95% CI of the ROR and IC remained above the criteria of significance throughout the study period, except 2013. The findings suggest disproportionately high reporting of pancreatitis in patients receiving TCZ as compared with other drugs. This marginally high reporting is not likely to be of immediate clinical concern and needs to be interpreted cautiously.
34473863 The first case of methotrexate-associated lymphoproliferative disorder presenting as folli 2021 Nov This is the first case of follicular T-cell lymphoma (FTCL) presenting as methotrexate-associated lymphoproliferative disorders (MTX-LPDs). A 69-year-old man treated rheumatoid arthritis with methotrexate presented with cervical swelling, hoarseness and fever. Imaging studies revealed multiple lymphadenopathy and lymphoma was suspected. Lymph node biopsy was performed to confirm the diagnosis. Pathologically, the lymph node was composed of atypical lymphocytes with a follicular growth pattern and area of necrosis. Immunohistochemical examination showed the atypical lymphocytes were positive for CD3, CD4, programmed cell death protein 1, and inducible T-cell co-stimulator. These findings are consistent with FTCL. During hospitalization, the patient's fever subsided and cervical lymphadenopathy improved, probably due to discontinuation of MTX. Here we presented the first case of FTCL presenting as MTX-LPDs. The T-cell phenotype MTX-LPDs are relatively rare and accounts for only 3.4%-6.3% of all MTX-LPD cases. Therefore, detailed clinicopathological features have not been clarified sufficiently. It is hoped that similar cases should be accumulated and studied to better understand the clinical and pathological features of this condition.
34239545 Alcohol Consumption and Risk of Common Autoimmune Inflammatory Diseases-Evidence From a La 2021 Purpose: Observational studies have suggested a protective effect of alcohol intake with autoimmune disorders, which was not supported by Mendelian randomization (MR) analyses that used only a few (<20) instrumental variables. Methods: We systemically interrogated a putative causal relationship between alcohol consumption and four common autoimmune disorders, using summary-level data from the largest genome-wide association study (GWAS) conducted on inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). We quantified the genetic correlation to examine a shared genetic similarity. We constructed a strong instrument using 99 genetic variants associated with drinks per week and applied several two-sample MR methods. We additionally incorporated excessive drinking as reflected by alcohol use disorder identification test score. Results: We observed a negatively shared genetic basis between alcohol intake and autoimmune disorders, although none was significant (r (g) = -0.07 to -0.02). For most disorders, genetically predicted alcohol consumption was associated with a slightly (10-25%) decreased risk of onset, yet these associations were not significant. Meta-analyzing across RA, MS, and IBD, the three Th1-related disorders yielded to a marginally significantly reduced effect [OR = 0.70 (0.51-0.95), P = 0.02]. Excessive drinking did not appear to reduce the risk of autoimmune disorders. Conclusions: With its greatly augmented sample size and substantially improved statistical power, our MR study does not convincingly support a beneficial role of alcohol consumption in each individual autoimmune disorder. Future studies may be designed to replicate our findings and to understand a causal effect on disease prognosis.
34224314 Alcohol as friend or foe in autoimmune diseases: a role for gut microbiome? 2021 Jan Alcohol is well known for promoting systemic inflammation and aggravating multiple chronic health conditions. Thus, alcohol may also be expected to serve as a risk factor in autoimmune diseases. However, emerging data from human and animal studies suggest that alcohol may in fact be protective in autoimmune diseases. These studies point toward alcohol's complex dose-dependent relationship in autoimmune diseases as well as potential modulation by duration and type of alcohol consumption, cultural background and sex. In this review, we will explore alcohol's pro- and anti-inflammatory properties in human and animal autoimmune diseases, including autoimmune diabetes, thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, experimental autoimmune encephalomyelitis and multiple sclerosis. We will also discuss potential mechanisms of alcohol's anti-inflammatory effects mediated by the gut microbiome.
34204101 The Function of the Histamine H4 Receptor in Inflammatory and Inflammation-Associated Dise 2021 Jun 6 Histamine is a pleiotropic mediator involved in a broad spectrum of (patho)-physiological processes, one of which is the regulation of inflammation. Compounds acting on three out of the four known histamine receptors are approved for clinical use. These approved compounds comprise histamine H1-receptor (H(1)R) antagonists, which are used to control allergic inflammation, antagonists at H(2)R, which therapeutically decrease gastric acid release, and an antagonist at H(3)R, which is indicated to treat narcolepsy. Ligands at H(4)R are still being tested pre-clinically and in clinical trials of inflammatory diseases, including rheumatoid arthritis, asthma, dermatitis, and psoriasis. These trials, however, documented only moderate beneficial effects of H(4)R ligands so far. Nevertheless, pre-clinically, H(4)R still is subject of ongoing research, analyzing various inflammatory, allergic, and autoimmune diseases. During inflammatory reactions in gut tissues, histamine concentrations rise in affected areas, indicating its possible biological effect. Indeed, in histamine-deficient mice experimentally induced inflammation of the gut is reduced in comparison to that in histamine-competent mice. However, antagonists at H(1)R, H(2)R, and H(3)R do not provide an effect on inflammation, supporting the idea that H(4)R is responsible for the histamine effects. In the present review, we discuss the involvement of histamine and H(4)R in inflammatory and inflammation-associated diseases of the gut.
34190695 Recombinant Production and One-Step Purification of IL-1Ra in Escherichia coli and Evaluat 2021 Jun BACKGROUND: Anakinra (Kineret®), an IL-1 receptor antagonist, is the first FDA-approved biologic drug for antagonizing IL-1 in patients with Rheumatoid arthritis. The less expensive production of this drug might help reduce the final therapeutic costs. OBJECTIVES: To evaluate the possibility of producing biologically active recombinant IL-1Ra by a single-step purification procedure mediated by a self-cleavable intein. METHODS: Soluble expression of the rIL-1Ra was performed in E. coli BL21 (DE3) infusion to intein1 of pTWIN-1 vector and its cleavage induction using an elution buffer (pH 6.8) at room temperature. Evaluation of the antagonizing efficacy of this protein in various concentrations was performed on A375 and HEK293 cells treated by a constant concentration of IL-1β (2 ng/mL). RESULTS: IPTG induction of E. coli BL21 (DE3) transformed with the recombinant pTWIN-1, revealed a band approximately in 45 kDa, which is related to the intein1-rIL-1Ra fusion protein in the SDS-PAGE. Moreover, protein purification was confirmed by observing a band in 18 kDa. Finally, the percentage of inhibition effects of rIL-1Ra and Kineret® against IL-1β was not statistically significant in IL-1-responsive A375 cells. The inhibition percentage was calculated as 86% in cells treated with 15µg/mL of rIL-1Ra, which was 96% for the inhibitory effects of the standard drug. CONCLUSION: In this study, biologically active soluble rIL1-Ra was successfully produced with high purity through a one-step procedure. This method can reduce the cost and time of production for this protein and might be applicable other biological products.
34088655 Tele-Rheumatology during the COVID-19 pandemic. 2022 Mar INTRODUCTION: During the Covid-19 pandemic strategies to prevent transmission of the viral infection obliged our hospital to promote virtual consultations. OBJETIVE: The objective of this study is to describe the results obtained with the previous strategy of transferring activity to teleconsultation during the period of maximum impact of the pandemic. MATERIAL AND METHODS: Between 16/03 and 10/05/2020 all successive consultations in our unit were performed in virtual rheumatology teleconference (RTC) format. The socio-demographic, geo-functional and clinical characteristics of all patients were collected; a numeric verbal scale (NVS) (where 0 = very dissatisfied to 10 = fully satisfied) was applied to assess the degree of satisfaction of the doctor/patient with the RTC. RESULTS: 469 TC were included. Most patients seen by RTC were women, mean age: 60,83 years. Only 16% had university education. The mean distance travelled for face-to face consultation is 33 Km with a mean total time of 2 h. Most individuals were diagnosed with osteoarthritis/soft tissue rheumatic diseases and/or osteoporosis; 21% had rheumatoid arthritis. The mean length of the TC was 9.64 min. We find more patient satisfaction with the TC when their level of education is higher (OR = 4.12); doctor satisfaction was higher when the individual was better able to manage the Internet (OR = 3.01). CONCLUSION: It is possible to transfer rheumatological care activity to TC with a considerable degree of satisfaction for both the patient and the doctor.