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ID PMID Title PublicationDate abstract
32113206 Travel and immunosuppressant medication. 2020 Mar BACKGROUND: The use of potent immunosuppressant medications is becoming more common, particularly the use of biologicals for a range of conditions such as rheumatoid arthritis and inflammatory bowel disease. OBJECTIVE: This article focuses on the implications of immunosuppressant medications for travel, including pre-travel vaccinations, minimising risks during travel and travelling with medicines. DISCUSSION: Pre-travel risk assessment is essential to prepare for safe travel. Live vaccines are contraindicated in people with significant immunosuppression because of the higher risk of adverse events and vaccine-associated disease. Inactivated vaccines can be used but may be less effective. Assessing the degree of immunocompromise in patients taking immunosuppressants includes considering both the medications and the underlying conditions. An individualised approach, often involving expert input, is needed to provide pre-travel health advice and immunisation. Planning ahead for travel is needed to minimise risks.
33200127 CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammat 2020 Nov 10 Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.
32248279 Correction to: Assessment of cervical spine involvement in rheumatoid arthritis patients i 2020 Jun In the original article, the first author's given name and family name were interchanged as provided by the authors in the original manuscript.
33445943 MAIT cells, their biological and medical significance. 2020 Winter MAIT cells are a separate cell population differentiating in the thymus. They are mostly present in the peripheral blood, liver, intestine, and lungs, less often in other tissues, and infrequently in the lymph nodes. The presentation molecules for MAIT cells are MR1 proteins. They are evolutionarily conserved and non-polymorphic, resemble class I HLA molecules, and are expressed by all cell types. They present bacterial and yeast vitamin metabolites which arise during the synthesis of vitamin B2. The effector functions of MAIT cells are promoted through cytokine synthesis. They also act cytotoxically, directly killing infected or tumour cells. MAIT cells may also play a role in pathological processes. Their involvement in the development of rheumatoid arthritis, systemic lupus erythematosus, autoimmune diabetes mellitus, Crohn's disease, and bronchial asthma has been demonstrated. In practical terms, MAIT cells are very sensitive to therapeutic doses of glucocorticoids. Treatment of patients with BA or chronic obstructive pulmonary disease with glucocorticoids increases their susceptibility to pneumonia, especially when caused by Streptococcus pneumoniae.
32902413 Caring for patients in a new pandemic: the necessity and challenges of observational resea 2020 Dec 1 Individuals with coronavirus disease 2019 (COVID-19) can develop pneumonia and a severe inflammatory response with excessive cytokine release known as the cytokine storm. The JAK inhibitor baricitinib, used to treat rheumatoid arthritis, reduces inflammation by modifying the cytokine pathway. In this issue of the JCI, Bronte, Ugel, and colleagues performed an observational longitudinal study to evaluate the use of baricitinib in 20 patients with COVID-19. The treated patients showed reduced levels of plasma IL-6, TNF, IL-1β, and phosphorylated STAT3 as well as swift lymphocyte restoration. Notably, these patients had a dramatically favorable clinical outcome. While bias can plague uncontrolled research, this study has biological credibility and warrants randomized, controlled studies.
32405173 Linking gut microbiota with the human diseases. 2020 The human gut is rich in microbes. Therefore, it is of interest to document data to link known human diseases with the gut microbiota. Various factors like hormones, metabolites and dietary habitats are responsible for shaping the microbiota of the gut. Imbalance in the gut microbiota is responsible for the pathogenesis of various disease types including rheumatoid arthritis, different types of cancer, diabetes mellitus, obesity, and cardiovascular disease. We report a review of known data for the correction of dysbiosis (imbalance in microbe population) towards improved human health.
31907605 Correction to: A prospective, longitudinal monocentric study on laser Doppler imaging of m 2020 Mar In the Original article, the legend of Figures 3 and 4 are interchanged and line number 387 is incomplete.
32877822 Determination of acid dissociation constants, enthalpy, entropy and Gibbs free energy of t 2020 Nov 30 Baricitinib is a drug used for the treatment of rheumatoid arthritis. It is a selective and reversible inhibitor of Janus kinases 1 and 2, which play an important role in signalling the pro-inflammatory pathway activated in autoimmune disorders such as rheumatoid arthritis. The pH-spectrophotometric and pH-potentiometric titrations allowed the measurement of three or four successive dissociation constants of Baricitinib. Baricitinib neutral LH(2) molecule was able to protonate into two soluble cations LH(4)(2+), LH(3)(+) and dissociate into two soluble anions LH(-) and L(2-) in pure water. The graph of molar absorption coefficients of differently protonated species versus wavelength indicated that the spectra ε(L), ε(LH), ε(LH2) were the nearly the same for these species and that the spectra ε(LH4) and ε(LH3) were also similar. In the pH range from 2-13, four pK(a)´s of spectra analysis were reliably estimated by REACTLAB at I =0.0020 mol. dm(-3) values pK(T)(a1) = 3.07, pK(T)(a2) = 3.87, pK(T)(a3) = 6.27, pK(T)(a4) = 12.78 at 25 °C and pK(T)(a1) = 3.00, pK(T)(a2) = 3.79, pK(T)(a3) = 6.12, pK(T)(a4) = 12.75 at 37 °C. Potentiometric pH-titration analysis for a higher concentration of 1 × 10(-3) mol. dm(-3) estimated with ESAB at I =0.0001 mol. dm(-3) values pK(T)(a1) = 3.69, pK(T)(a2) = 3.81, pK(T)(a3) = 4.73 at 25 °C and pK(T)(a1) = 3.62, pK(T)(a2) = 3.73, pK(T)(a3) = 4.43 at 37 °C. Molar enthalpy ΔH°, molar entropy ΔS° and Gibbs free energy ΔG° were calculated from the spectra using a dependence ln K to 1/T.
32707665 Silicon Nanofluidic Membrane for Electrostatic Control of Drugs and Analytes Elution. 2020 Jul 19 Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such as diabetes, hypertension, rheumatoid arthritis. Several triggered systems for drug delivery have been demonstrated. However, they mostly rely on continuous external stimuli, which hinder their application for long-term treatments. In this work, we investigated a silicon nanofluidic technology that incorporates a gate electrode and examined its ability to achieve reproducible control of drug release. Silicon carbide (SiC) was used to coat the membrane surface, including nanochannels, ensuring biocompatibility and chemical inertness for long-term stability for in vivo deployment. With the application of a small voltage (≤ 3 V DC) to the buried polysilicon electrode, we showed in vitro repeatable modulation of membrane permeability of two model analytes-methotrexate and quantum dots. Methotrexate is a first-line therapeutic approach for rheumatoid arthritis; quantum dots represent multi-functional nanoparticles with broad applicability from bio-labeling to targeted drug delivery. Importantly, SiC coating demonstrated optimal properties as a gate dielectric, which rendered our membrane relevant for multiple applications beyond drug delivery, such as lab on a chip and micro total analysis systems (µTAS).
32023488 Novel multiparticulate pH triggered delayed release chronotherapeutic drug delivery of cel 2020 Apr 15 This study aimed to prepare novel colon targeted celecoxib-β-cyclodextrin (CXB-β-CD) inclusion complex loaded eudragit S 100 (ES100) microparticles for chronotherapy of rheumatoid arthritis (RA) which is an innovative approach, never reported before, for the fabrication of CXB-β-CD complex in the form of microparticles and its colon targeting. CXB was complexed with β-cyclodextrin by kneading technique and we evaluated the effect of β-CD on saturation solubility of CXB. Microparticles were developed by oil-in-oil emulsion solvent evaporation technique and formulation variables (polymer conc, surfactant conc and stirring speed) were optimized by using three-factor three-level Box-Behnken design (BBD). SEM imaging revealed smooth, uniform and spherical shape microparticles. There was 7.3 fold increases in saturation solubility of CXB-β-CD inclusion complex in distilled water as compared to pure CXB. Particle size was in the range of 50.42 µm to 238.38 µm with entrapment efficiency of 68.47% to 91.65%. Biphasic drug release pattern was found i.e initially delayed release in stomach and small intestine followed by fast release at colonic pH. Response variable results achieved from optimized formulation were very close to the response values suggested by BBD signifying the actual reliability and robustness of BBD in the fabrication of colon targeted CXB-β-CD microparticles. The comparison of CXB-β-CD optimized formulation with optimized formulation containing pure CXB showed increase in drug release due to enhancement of water solubility of CXB-β-CD inclusion complex. So, it can be concluded that CXB-β-CD loaded ES100 microparticles can be successfully fabricated with enhanced solubility for the chronotherapy of rheumatoid arthritis.
32021468 Incidence of Free of Charge Physiotherapy in a Danish National Cohort of Stroke, Parkinson 2020 BACKGROUND: Denmark is a welfare state with a publically funded healthcare system that includes the right to free of charge physiotherapy (FCP) for patients with chronic or progressive disease who fulfill strict criteria. The aim of this study was to investigate the incidence of referral to FCP in patients with a hospital diagnosis of stroke, multiple sclerosis (MS), Parkinson's disease (PD) and rheumatoid arthritis (RA) between 2007 and 2016. METHODS: The study was register-based and included data from The Danish National Patient Registry and The National Health Service Registry. The study population included the four largest disease groups receiving FCP in Denmark. The incidence of receiving FCP was reported as the cumulated incidence proportion (CIP). RESULTS: The study showed that FCP was mainly initiated within the first 2 years after diagnosis. The 2-year CIP was 8% for stroke patients, 53% for PD patients, 49% for MS patients, and 16% for RA patients. The proportion of patients referred to FCP generally increased over the period of the study due to more patients being referred from medical specialists in primary care. CONCLUSION: This study found substantial differences in the incidence of referral to FCP in a Danish population of stroke, PD, MS and RA patients.
31985294 A randomized phase I pharmacokinetic trial comparing the potential biosimilar adalimumab ( 2020 Mar Background: CinnoRA® (CinnaGen, Iran) is a biosimilar candidate for the reference adalimumab, Humira® (AbbVie, USA). This study aimed to compare the pharmacokinetics, safety, and tolerability of these products in healthy participants.Research design and methods: In this phase-I, randomized, double-blind trial, 74 healthy adult volunteers were randomized in a 1:1 ratio to receive a single 40 mg subcutaneous injection of CinnoRA® or Humira®. Serum concentrations of adalimumab were analyzed using a validated enzyme-linked immunosorbent assay and were evaluated by non-compartmental methods. Pharmacokinetic equivalence between groups was determined using the standard equivalence margins of 0.80 to 1.25.Results: The baseline characteristics were similar between study groups. Mean values of area under the serum concentration-time curve from time zero to infinity (AUC(inf)) and maximum serum concentration (C(max)) were similar in study groups and the 90% confidence intervals for the geometric mean ratios of AUC(inf) and C(max) were within the prespecified equivalence margins. There were no deaths and the total number of treatment-related adverse events was not statistically different between groups (p-value = 0.19).Conclusions: The results clearly showed the pharmacokinetic similarity of the biosimilar adalimumab to the originator. CinnoRA® was safe and well-tolerated in healthy volunteers, with no significant differences in safety from the reference product.Trial Registration: The trial is registered at ClinicalTrials.gov (# NCT03273192).
33188918 Profiling and targeting connective tissue remodeling in autoimmunity - A novel paradigm fo 2021 Jan Connective tissue (ConT) remodeling is an essential process in tissue regeneration, where a balanced replacement of old tissue by new tissue occurs. This balance is disturbed in chronic diseases, often autoimmune diseases, usually resulting in the buld up of fibrosis and a gradual loss of organ function. During progression of liver, lung, skin, heart, joint, skeletal and kidney diseasesboth ConT formation and degradation are elevated, which is tightly linked to immune cell activation and a loss of specific cell types and extracellular matrix (ECM) structures that are required for normal organ function. Here, we address the balance of key general and organ specific components of the ECM during homeostasis and in disease, with a focus on collagens, which are emerging as both structural and signaling molecules harbouring neoepitopes and autoantigens that are released during ConT remodeling. Specific collagen molecular signatures of ConT remodeling are linked to disease activity and stage, and to prognosis across different organs. These signatures accompany and further drive disease progression, and often become detectable before clinical disease manifestation (illness). Recent advances allow to quantify and define the nature of ConT remodeling via blood-based assays that measure the levels of well-defined collagen fragments, reflecting different facets of ConT formation and degradation, and associated immunological processes. These novel serum assays are becoming important tools of precision medicine, to detect various chronic and autoimmune diseases before their clinical manifestation, and to non-invasively monitor the efficacy of a broad range of pharmacological interventions.
33126276 The Reliability of Ultrasound in the Assessment of Hyaline Cartilage in Rheumatoid Arthrit 2020 Oct 30 PURPOSE:  i) To assess the inter- and intra-observer reliability of ultrasound (US) in the evaluation of the hyaline cartilage (HC) of the metacarpal head (MH) in patients with rheumatoid arthritis (RA) and in healthy subjects (HS) both qualitatively and quantitatively. ii) To calculate the smallest detectable difference (SDD) of the MH cartilage thickness measurement. iii) To correlate the qualitative scoring system and the quantitative assessment. MATERIALS AND METHODS:  US examination was performed on 280 MHs of 20 patients with RA and 15 HS using a very high frequency probe (up to 22 MHz). HC status was evaluated both qualitatively (using a five-grade scoring system) and quantitatively (using the average value of the longitudinal and transverse measures). The HC of MHs from II to V metacarpophalangeal joint of both hands were scanned independently on the same day by two rheumatologists to assess inter-observer reliability. All subjects were re-examined using the same scanning protocol and the same US setting by one sonographer after a week to assess intra-observer reliability. RESULTS:  The inter-observer agreement and intra-observer agreement were moderate to substantial (k = 0.66 and k = 0.73) for the qualitative scoring system and high (ICC = 0.93 and ICC = 0.94) for the quantitative assessment. The SDD of the MH cartilage thickness measurement was 0.09 mm. A significant correlation between the two scoring systems was found (r = -0.35; p < 0.001). CONCLUSION:  The present study describes the main methodological issues of HC assessment. Using a standardized protocol, both the qualitative and the quantitative scoring systems can be reliable.
33101117 Management and Treatment of Patients With Major Depressive Disorder and Chronic Diseases: 2020 In patients with physical chronic diseases, the prevalence of major depressive disorder (MDD) is approximately 2- to 3-fold higher than in the general population, and it can reach up to 20-40%. The comorbidity of MDD with chronic medical diseases is associated with poorer quality of life, increased medical symptom burden, poor adherence to self-care regimens, increased risk of functional impairment, morbidity, and mortality, and also higher medical costs. Despite this evidence, in routine practice, psychological issues and concerns are frequently inadequately managed. This consensus document proposes that a proper diagnosis, a multidisciplinary approach, and a personalized treatment plan would allow patients with MDD and chronic comorbidities to be more compliant, to improve the outcomes, to reduce possible relapses in the long term, and to prevent or better manage complications and adverse events. This proposal might be useful for any health professionals who deal with patients with chronic diseases, as it can help to pay more attention to the emotional impact of these conditions, in particular in terms of depressive symptoms.
33029648 Edema-like marrow signal intensity: a narrative review with a pictorial essay. 2021 Apr The term edema-like marrow signal intensity (ELMSI) represents a general term describing an area of abnormal signal intensity at MRI. Its appearance includes absence of clear margins and the possibility of exceeding well-defined anatomical borders (for example, physeal scars). We can define "ELMSI with unknown cause" an entity where the characteristic MR appearance is associated with the absence of specific signs of an underlying condition. However, it is more often an important finding indicating the presence of an underlying disease, and we describe this case as "ELMSI with known cause." It presents a dynamic behavior and its evolution can largely vary. It initially corresponds to an acute inflammatory response with edema, before being variably replaced by more permanent marrow remodeling changes such as fibrosis or myxomatous connective tissue that can occur over time. It is important to study ELMSI variations over time in order to evaluate the activity state and therapeutic response of an inflammatory chronic joint disease, the resolution of a trauma, and the severity of an osteoarthritis. We propose a narrative review of the literature dealing with various subjects about this challenging topic that is imaging, temporal evolution, etiology, differential diagnoses, and possible organization, together with a pictorial essay.
32509155 Moxibustion benignantly regulates circadian rhythm of REV-ERBα in RA rats. 2020 The key clinical symptoms and previous findings of RA show a circadian variation, with more prominent joint swelling, stiffness, and pain occurring in the early morning. Moxibustion is able to relieve RA in various pass ways, however, there is no verifying study results for the pathological rhythm of RA. Therefore, we conducted this work to verify whether moxibustion could adjust RA circadian rhythm according to regulate core clock genes. Based on these previous findings that circadian timekeeping is disturbed in RA at molecular level, the aim of this study was to observe the influence of moxibustion on expression level and circadian rhythm of REV-ERBα at different tissues of RA rats. Furthermore, the expression level of core clock genes closely related to RA were evaluated by RT-PCR. 96 SD rats were randomly assigned as 1:1:1:1 ratio to 4 groups for normal control group, RA model group, 5-7 am moxibustion group, and 5-7 pm moxibustion group. RT-PCR was used to measure the relatively expression quantity of REV-ERBα, CLOCK, BMAL1, and PER2 in hypothalamus, hippocampus, and adrenal gland. In RA rats, the expression level of REV-ERBα mRNA were up-regulated in different tissues, and moxibustion potentially up-regulated them in different degrees. In untreated RA rats, the circadian rhythm of REV-ERBα mRNA in hippocampus and adrenal gland both disappeared (P>0.05) and moxibustion was able to recover them (P<0.05). The expression level of CLOCK and PER2 mRNA in hippocampus and adrenal gland were down-regulated significantly (P<0.05) in RA model rats, while moxibustion up-regulated both of them in hippocampus (P<0.05). These results suggested together that moxibustion can benign regulate circadian rhythm of REV-ERBα in different tissues of RA rats. It was revealed that moxibustion not only recovered the losing diurnal oscillation of REV-ERBα in hippocampus and adrenal gland, but also adjusted the circadian rhythm of REV-ERBα in hypothalamus, hippocampus, and adrenal gland to close the normal circadian pattern.
32021661 Risk of comorbidities in patients diagnosed with chronic urticaria: A nationwide registry- 2020 Jan BACKGROUND: The autoimmune profile of Chronic Urticaria (CU) patients is an increasing topic of interest. Associated diseases suggest shared pathogenic pathways, and they may provide important knowledge on specific targets for future treatment models. In this study we examined the prevalence and risk of comorbidities in CU. METHODS: The Danish National Patient Registry was used to identify all CU patients from 1994 to 2015. Five of 5 specialized dermatological units in Denmark were covered. Analyses were conducted as a nested case control study and a matched cohort study. CSU patients were matched 1:10 on age and sex to an otherwise random group of people from the background population. RESULTS: A total of 12,185 CU patients were identified, with an overweight of female cases (69% versus 32%). There was an overrepresentation of mast cell mediated diseases including mastocytosis and anaphylaxis, as well as atopic diseases including type 1 allergies and atopic dermatitis. The prevalence of rheumatoid arthritis, systemic lupus erythematosus, thyroiditis and vitiligo was also increased, as was the prevalence of depression. CU patients who did not have any of the co-morbidities at the time of their CU diagnosis had an increased risk of developing both mast cell mediated diseases, atopic diseases, and autoimmune diseases excluding thyroiditis and diabetes. CONCLUSION: The autoimmune profile of the comorbidities of CU was demonstrated with an evident risk of developing rheumatoid arthritis. CU patients were also at increased risk of either having or achieving depression. Mast cell related diseases seemed to be overrepresented, although registry data within this disease category are questionable and similar to symptoms of CU to the untrained eye. Thus, CU patients constitute a multimorbid group of patients, which must be recognized among treating physicians.
31887802 Detection of Anti-Extractable Nuclear Antigens in Patients with Systemic Rheumatic Disease 2020 Jan PURPOSE: Testing for autoantibodies to extractable nuclear antigens (ENAs) plays an important role in the diagnosis and management of systemic rheumatic disease. Currently, no gold standard tests are available for detecting anti-ENAs. To address this gap, we aimed to identify an assay that exhibits satisfactory diagnostic performance in the detection of five common anti-ENAs by comparing two commonly used assays, an automated fluorescent enzyme immunoassay (FEIA) and a microplate ELISA assay. MATERIALS AND METHODS: Sera from 100 patients with systemic rheumatic disease were collected and assayed with FEIA and microplate ELISA to detect anti-ENAs. Statistical analyses were performed to check the agreement rate between the two platforms using kappa coefficients. Analytical sensitivity and specificity for each assay were calculated. RESULTS: The concordance rates between ELISA and FEIA ranged from 89% for anti-RNP to 97% for anti-Scl-70, and the kappa coefficients of the two assays were in the range of 0.44 to 0.82. Between the two assays, a significant difference in sensitivity and specificity was seen only for anti-Sm and anti-RNP, respectively. CONCLUSION: In this study, FEIA and ELISA showed comparable efficiency for detecting anti-ENAs.
31301390 Rituximab as a trigger factor of medication-related osteonecrosis of the jaw. A case repor 2020 Jun Rituximab, an anti-CD20 monoclonal antibody, is an effective treatment for rheumatoid arthritis. Here we report the case of a patient with rheumatoid arthritis, having taken risedronate for 14 months to prevent corticosteroid-induced osteoporosis, more than 2 years ago, who presented osteonecrosis of jaw following herpetic gingivostomatitis two weeks after the beginning of a rituximab treatment associated with her usual anti-rheumatic drugs. Eight weeks later, no bone and/or gum healing was observed and a stage 2 medication-related osteonecrosis of the jaw (MRONJ) was diagnosed. A conservative approach was decided with antiseptic mouth washes, low-level laser treatment (LLLT) and systemic therapy with teriparatide. Complete mucosal coverage was obtained after more two years of follow-up. We suggest that rituximab as immunosuppressant might be a cause or a decompensating factor of MRONJ. Non-surgical periodontal treatment with LLLT and teriparatide are candidates for the treatment of MRONJ.