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ID PMID Title PublicationDate abstract
32043780 Sicca Syndrome Induced by Immune Checkpoint Inhibitor Therapy: Optimal Management Still Pe 2020 Feb Commenting on a recently published article on sicca syndrome linked to immune checkpoint inhibitor therapy, this letter to the editor shares another viewpoint on the management of this immune‐related adverse event.
32767314 LncRNA H19 inhibitor represses synovial cell proliferation and apoptosis in rats with rheu 2020 Aug The article "LncRNA H19 inhibitor represses synovial cell proliferation and apoptosis in rats with rheumatoid arthritis via Notch signaling pathway, by L.-Q. Zhi, Q. Zhong, J.-B. Ma, L. Xiao, S.-X. Yao, X. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (8): 4088-4094-DOI: 10.26355/eurrev_202004_20985-PMID: 32373945" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20985.
31980965 Correction to: Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model 2020 Jan 24 The article was published with an incomplete title. The complete title is "Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis" The original article has been corrected.
32307922 Impaired Interleukin-27-Mediated Control of CD4+ T Cell Function Impact on Ectopic Lymphoi 2020 Sep OBJECTIVE: Ectopic lymphoid structures (ELS) develop at sites of infection, autoimmunity, and cancer. In patients with Sjögren's syndrome (SS), ELS support autoreactive B cell activation and lymphomagenesis. Interleukin-27 (IL-27) is a key regulator of adaptive immunity and limits Th17 cell-driven pathology. We undertook this study to elucidate the role of IL-27 in ELS formation and function in autoimmunity using a murine model of sialadenitis and in patients with SS. METHODS: ELS formation was induced in wild-type and Il27ra(-/-) mice via salivary gland (SG) cannulation of a replication-deficient adenovirus in the presence or absence of IL-17A neutralization. In SG biopsy samples, IL-27-producing cells were identified by multicolor immunofluorescence microscopy. Lesional and circulating IL-27 levels were determined by gene expression and enzyme-linked immunosorbent assay. The in vitro effect of IL-27 on T cells was assessed using fluorescence-activated cell sorting and cytokine release. RESULTS: In experimental sialadenitis, Il27ra(-/-) mice had larger and more hyperactive ELS (focus score; P < 0.001), increased autoimmunity, and an expanded Th17 response (P < 0.001), compared to wild-type mice. IL-17 blockade in Il27ra(-/-) mice suppressed the aberrant ELS response (B and T cell reduction against control; P < 0.01). SS patients displayed increased circulating IL-27 levels (P < 0.01), and in SG biopsy samples, IL-27 was expressed by DC-LAMP+ dendritic cells in association with CD3+ T cells. Remarkably, in SS T cells (but not in T cells from patients with rheumatoid arthritis or healthy controls), IL-27-mediated suppression of IL-17 secretion was severely impaired and associated with an aberrant interferon-γ release upon IL-27 stimulation. CONCLUSION: Our data indicate that the physiologic ability of IL-27 to limit the magnitude and function of ELS through control of Th17 cell expansion is severely impaired in SS patients, highlighting a defective immunoregulatory checkpoint in this condition.
32897213 [Research progress of correlation between periodontal pathogens and systemic diseases]. 2020 May 30 Periodontal pathogens are the main pathogenic factor of periodontitis. Periodontal pathogens have a large variety of virulence factors such as lipopolysaccharide, fimbriae and proteases, which enables the pathogens to infect periodontal tissues and stimulate the secretion of inflammatory cytokines, causing chronic systemic inflammation. Periodontal pathogens may invade multiple systems such as the circulatory system, immune system, respiratory system and digestive system to cause systematic diseases. Recent studies have shown that periodontal pathogens may have close relations with systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and cancer. Among the periodontal pathogens, Porphyromonas gingivalis can be found in atherosclerotic plaques to impairing the function of the vascular endothelium; Porphyromonas gingivalis may also increase the level of inflammatory factors such as TNF-α to promote insulin resistance and diabetes. Many of the periodontal pathogens such as Porphyromonas gingivalis, Tannerella forsythia and Prevotella intermedia can be detected in the synovial fluid of rheumatoid arthritis patients, suggesting their involvement in the pathogenesis of rheumatoid arthritis. Fusobacterium nucleatum may cause alterations in the intestinal microbiome in mice and promote the occurrence of intestinal tumors. Herein we review the recent progresses in the relationship between periodontal pathogens and systemic diseases.
31830499 Role of allograft inflammatory factor-1 in pathogenesis of diseases. 2020 Feb Allograft inflammatory factor-1 (AIF-1) is a 17 kDa calcium-binding protein produced by monocytes, macrophages, and lymphocytes; its synthesis is induced by INF-γ. The AIF-1 gene is located in the major histocompatibility complex (MHC) class III region on chromosome 6p21.3, surrounded by surface glycoprotein genes and complement cascade protein genes as well as TNF-α, TNF-β, and NF-κB genes. Increased expression of AIF-1 was observed in several diseases, including endometriosis, breast cancer, atherosclerosis, rheumatoid arthritis, and fibrosis. In this review, we summarise the role of AIF-1 in allograft rejection and the pathogenesis of diseases.
33138014 The Effectiveness and Retention Rate of Iguratimod in Japanese Rheumatoid Arthritis Patien 2020 Oct 29 (1) Background: We evaluated the clinical response of iguratimod (IGU) in patients with rheumatoid arthritis (RA) being treated with or without methotrexate (MTX) over 54 weeks. (2) Methods: 106 patients with RA undergoing IGU were retrospectively observed. RA patients were divided into those treated with MTX+IGU (n = 35) and those treated with IGU (n = 71). The primary endpoint was the clinical response of the Disease Activity Score assessing 28 joints with C-reactive protein (DAS28-CRP) differences in the changes from baseline to 54 weeks between MTX+IGU and IGU groups. Secondary endpoints, such as the clinical response, retention rate, and safety, were evaluated. (3) Results: The DAS28-CRP difference in the changes between the two groups were -0.2. DAS28-CRP were significantly reduced from the baseline in the MTX+IGU and IGU groups (-1.43 and -1.20 from baseline, respectively). The retention rates were 71.4% in the MTX+IGU groups and 59.2% in the IGU groups (p = 0.16). Adverse events were observed in a total of 6 (17.1%) MTX+IGU patients and 20 (28.2%) IGU patients (p = 0.21). (4) Conclusions: IGU therapy may be a useful treatment option for patients who cannot be treated with MTX.
32879574 Prevalence of cervical spine instability among Rheumatoid Arthritis patients in South Iraq 2020 Sep AIM OF THE WORK: This study analysed the prevalence of cervical spine instability in Rheumatoid Arthritis (RA) patients following at a single centre in Basrah. PATIENTS AND METHODS: Data were collected directly from patients through cervical spine examinations. Each patient was sent for dynamic (flexion and extension) lateral cervical radiographic imaging to assess the presence of atlantoaxial subluxation (AAS), superior migration of the odontoid (SMO) and sub-axial subluxation (SAS). Patients with positive radiographic findings were sent for MRI scans of the cervical spine to assess neurological compression. RESULTS: The prevalence rate of cervical spine instability in RA was 15/203 (7.4%) of the total sample, occurring primarily in patients of 37-65 years old (mean: 48 ± 8.9 years), were 3/15 (20%) aymptomatic. The majority (60%) being at the moderate stage of the disease activity (using a Clinical Disease Activity Index [CDAI). In terms of type of cervical spine involvement, isolated AAS was found to have the highest occurrence (73.3%), followed by combined SAS and SMO (13.3%), combined AAS and SMO (6.7%), and combined AAS and SAS (6.7%). A significant relationship was found between the type of cervical spine involvement in RA and a disease onset duration, disease activity, body mass index and peripheral erosion with P value < 0.05. CONCLUSION: Cervical spine subluxation in RA patients may be asymptomatic It is therefore essential to obtain a dynamic radiographic image of the cervical spine in order to diagnose cervical spine involvement and protect the patient from severe outcomes.The clinical trial registration number included in a the official document from Ministry of Higher Education and Science Research/Basrah University/Faculty of Medicine to Basrah Health Directorate/Research and Development Division is 72/3588 in 7 Jan 2017.
35025370 Matrix Metalloproteinase-Responsive PEGylated Lipid Nanoparticles for Controlled Drug Deli 2020 May 18 Rheumatoid arthritis (RA) is an autoimmune disorder. It causes inflammation, swelling, and pain in the joints of the human body. Overexpressed matrix metalloproteinases (MMPs) at the inflammatory sites of RA are a target in the construction of inflammation-responsive drug delivery vehicles for enhancing the therapeutic effect of anti-inflammatory drugs in the treatment of RA. In this paper, we report MMP-responsive PEGylated lipid nanoparticles through the co-assembly of triglycerol monostearate (TGMS) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-poly(ethyleneglycol) (DSPE-PEG(2000)) in which the ester bond of TGMS is cleavable by MMPs and the PEG chain provides a stealth layer. The lipid nanoparticles show high biocompatibility, extended blood circulation, and preferential distribution in the inflammatory joints of RA. The loaded dexamethasone (Dex) can be rapidly released from the lipid nanoparticles in response to MMPs. After being intravenously administered to arthritic rats, Dex-loaded MMP-responsive PEGylated lipid nanoparticles significantly reduce the degree of joint swelling and inhibit the production of TNF-α and IL-1β in joint tissues. These results demonstrate that MMP-responsive PEGylated lipid nanoparticles are a smart drug vehicle for the treatment of RA with improved therapeutic efficacy.
32292416 Detection and Comparative Analysis of Methylomic Biomarkers of Rheumatoid Arthritis. 2020 Rheumatoid arthritis (RA) is a common autoimmune disorder influenced by both genetic and environmental factors. To investigate possible contributions of DNA methylation to the etiology of RA with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs. This study hypothesized that methylomic biomarkers might facilitate accurate RA detection. A comprehensive series of biomarker detection algorithms were utilized to find the best methylomic biomarkers for detecting RA patients using the methylomic data of the peripheral blood samples. The best model achieved 100.00% in accuracy (Acc) with 81 methylomic biomarkers and a 10-fold cross-validation (10FCV) strategy. Some of the methylomic biomarkers were experimentally confirmed to be associated with the onset or development of RA. It is also interesting to observe that many of the detected biomarkers were from chromosome Y, supporting the knowledge that RA has a significant gender discrepancy.
32153635 Association of BLK and BANK1 Polymorphisms and Interactions With Rheumatoid Arthritis in a 2020 INTRODUCTION: BLK has been identified as a risk factor to rheumatoid arthritis (RA) primarily in Asian or European-derived populations. However, this finding has not been evaluated in other populations such as Latin-Americans, except for Colombians. On the other hand, BANK1 single nucleotide variants (SNVs) have been scarcely studied in RA patients. OBJECTIVE: The aim of this study was to determine whether the BLK rs2736340T/C, rs13277113A/G, and BANK1 rs10516487G/A (R61H) and rs3733197G/A (A383T) polymorphisms are risk factors to RA in a sample of patients from Central Mexico. MATERIALS AND METHODS: We studied 957 women; 487 controls and 470 patients with RA by means of a TaqMan® SNP genotyping assay with fluorescent probes for the BLK rs13277113A/G, rs2736340T/C and BANK1 10516487G/A (R61H) and rs3733197G/A (A383T) variants. RESULT: The BLK rs2736340T/C and rs13277113A/G variants were associated with risk for RA: C vs T; OR 1.39, p = 0.001, and G vs A; OR 1.37, p = 0.004, respectively. In addition, there was also an association between BANK1 R61H and RA: A vs G; OR 1.49, p = 0.003, but no with BANK1 A383T. We also identified an interaction significant between genotypes of BLK rs2736340T/C-BANK1 rs10516487G/A and RA: OR 1.65, p = 0.0001. CONCLUSIONS: Our data suggest that both BLK and BANK1 confer susceptibility to RA in Mexican patients. The individual association of BANK1 rs1054857G/A with RA had not been previously reported in a particular population (except for pooled patients from several countries), therefore, our study presents the first evidence of association between this BANK1 variant and RA.
32348214 IL-37 As a Potential Biotherapeutics of Inflammatory Diseases. 2020 Interleukin-37 (IL-37) was discovered as a new member of pro-inflammatory IL-1 superfamily. However, further studies suggested that IL-37 plays a critical anti-inflammatory role in innate and adaptive immunity. IL-37 may suppress the inflammatory process via intracellular SMAD family member 3 (SMAD3) and extracellular IL-18 Receptor alpha (IL-18Rα) signaling pathway, respectively. Meanwhile, the abnormal expression of IL-37 was observed in immune-mediated inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, atherosclerosis, systemic lupus erythematosus, asthma, and multiple sclerosis, which suggest IL-37 is a potential therapeutic target for these diseases. In this review, we summarize the anti-inflammatory mechanism of IL-37 and discuss the critical roles of IL-37 in the pathogenesis of these diseases. Further studies are required to confirm the effectiveness of IL-37 as a novel target for these inflammatory diseases.
33362560 IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthr 2020 Fertility issues are common amongst women with rheumatoid arthritis (RA). Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), known key players in RA pathogenesis, have been associated with reproductive disorders. This study investigates the role of these cytokines in decreased fertility in women with active RA. Preconception cytokine measurements of 61 patients from the PARA-cohort, a prospective study on RA and pregnancy, were studied in relation to time to pregnancy as a measure for fertility. IL-6 levels were higher in patients with a time to pregnancy longer than 1 year (p = 0.016). Survival analysis of patients stratified by high or low serum IL-6 levels, shows a prolonged time to pregnancy in the high IL-6 group (p = 0.045). Univariate cox regression analysis of IL-6 in relation to time to pregnancy as well as multivariate cox regression analysis correcting for age, disease activity, nulliparity, NSAID use and prednisone use were performed, with hazards ratios for log transformed IL-6 of 0.68 (95% CI: 0.51-0.93, p = 0.015) and 0.66 (95% CI: 0.43-0.99, p = 0.044), respectively. For TNFα, no association with time to pregnancy was found. This study shows that high IL-6, but not TNFα, is associated with decreased fertility in women with RA. This finding provides a rationale to therapeutically target the IL-6 pathway in the time period before pregnancy. More research in the form of large cohort studies on drug safety and the effect of bDMARDS on fertility is needed for implementation of treatment strategies directed at fertility issues in women with RA.
31907758 Comparative Cost per Response for 4 Clinical Endpoints with Tocilizumab Monotherapy vs Ada 2020 Mar INTRODUCTION: The cost-effectiveness of different biologic therapies can be an important component in guiding treatment decisions for patients with rheumatoid arthritis (RA). The objective of this study was to compare drug and adverse event costs and cost per successful clinical response with tocilizumab (TCZ) monotherapy vs adalimumab (ADA) monotherapy in patients with RA in a phase 4 clinical trial. METHODS: Patients received either TCZ intravenously every 4 weeks or ADA subcutaneously every 2 weeks for 24 weeks. Drug and administration costs were based on wholesale acquisition costs and the Centers for Medicare and Medicaid, respectively. Outcomes included patient-level drug costs, cost of hospitalization due to adverse events, and cost per response. Cost per response was calculated by dividing the mean drug plus administration cost by the proportion of patients achieving Disease Activity Score in 28 joints (DAS28) < 2.6 (remission) or 20%, 50%, or 70% improvement in response per the American College of Rheumatology (ACR20/50/70). Hospitalization costs were calculated using the daily hospital cost and number of hospital days. RESULTS: Among the 163 patients treated with TCZ and 162 patients treated with ADA, mean total drug and administration costs per patient over 24 weeks were $18,290.60 and $25,623.10, respectively. Mean drug and administration costs per each clinical response achieved were lower with TCZ than with ADA (DAS28 < 2.6: $45,868 vs $244,174; ACR20: $28,127 vs $51,887; ACR50: $38,720 vs $92,244; ACR70: $56,253 vs $143,136). The total hospital days were 32 days with TCZ and 43 days with ADA; mean hospital costs per patient were $484.50 with TCZ and $651.10 with ADA. CONCLUSION: In this comparative assessment, the cost to achieve all 4 clinical endpoints was lower for patients receiving TCZ than for those receiving ADA.
31866485 A Qualitative Metasynthesis of the Experience of Fatigue Across Five Chronic Conditions. 2020 Jun CONTEXT: Fatigue is a symptom reported by patients with a variety of chronic conditions. However, it is unclear whether fatigue is similar across conditions. Better understanding its nature could provide important clues regarding the mechanisms underlying fatigue and aid in developing more effective therapeutic interventions to decrease fatigue and improve quality of life. OBJECTIVES: To better understand the nature of fatigue, we performed a qualitative metasynthesis exploring patients' experiences of fatigue across five chronic noninfectious conditions: heart failure, multiple sclerosis, rheumatoid arthritis, chronic kidney disease, and chronic obstructive pulmonary disease. METHODS: We identified 34 qualitative studies written in the last 10 years describing fatigue in patients with one of the aforementioned conditions using three databases (Embase, PubMed, and CINAHL). Studies with patient quotes describing fatigue were synthesized, integrated, and interpreted. RESULTS: Across conditions, patients consistently described fatigue as persistent overwhelming tiredness, severe lack of energy, and physical weakness that worsened over time. Four common themes emerged: running out of batteries, a bad life, associated symptoms (e.g., sleep disturbance, impaired cognition, and depression), and feeling misunderstood by others, with a fear of not being believed or being perceived negatively. CONCLUSION: In adults with heart failure, multiple sclerosis, rheumatoid arthritis, chronic kidney disease, and chronic obstructive pulmonary disease, we found that fatigue was characterized by severe energy depletion, which had negative impacts on patients' lives and caused associated symptoms that exacerbated fatigue. Yet, fatigue is commonly misunderstood and inadequately acknowledged.
33182835 Ultrasound as a Biomarker in Rheumatic Diseases. 2020 Nov 10 Rheumatic diseases are a heterogeneous group of disorders which often affect the musculoskeletal system. Given the lack of definitive testing, there are limited diagnostic tools at clinicians' disposal. Over the recent decades, ultrasonography has gained widespread use within rheumatology due to its accessibility, safety, and relatively low cost. This review describes the clinical utility of ultrasound as a biomarker in the diagnosis and management of several rheumatic diseases.
31924392 [Adult-onset Still's disease complications]. 2020 Mar Adult-onset Still's disease (AOSD), first described in 1971 by Bywaters, is a rare systemic auto-inflammatory disorder of unknown etiology, characterized by a symptomatic triad associating prolonged fever, polyarthritis and rash. The management of this disease has significantly improved since its first description, and, although the overall prognosis of the AOSD is good, with a low attributable mortality, below 3% (but up to 18% depending on the series), some rare complications are still possible, can be life-threatening and change the prognosis of the disease. A literature search was performed to review AOSD's complications: reactive hemophagocytic lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiovascular (pericarditis, myocarditis, HTAP) or pulmonary complications, neurologic, renal complications, and AA amyloidosis. For most of AOSD-related complications, corticosteroids remain the first-line treatment, in association with supportive care measures in case of severe complications. In case of inadequate response, multidisciplinary care with concil from a referral center is advised, and IL-1 or IL-6 blockers, but also ciclosporine, are the molecule to use in second intention.
33156294 [Dry mouth. Case histories from a saliva clinic]. 2020 Oct Three patients who were referred to the saliva of the Center for Special Care Dentistry (Stichting Bijzondere Tandheelkunde, SBT) in Amsterdam clearly demonstrate that in the case of patients suffering from xerostomia, it can be useful to have the saliva secretion rate determined and to take saliva into account in the aetiology and in developing a dental treatment plan. In the first case, a 39-year-old woman presented with dry mouth associated with Sjögren's syndrome. A fair degree of saliva secretion was still possible. The teeth were characterised by wear, caries lesions and sensitivity. The second patient was a 42-year-old man suffering from dry mouth associated with the use of medications. His teeth were weakened to the point of deciding to create conventional full dentures, despite a possible moderate prognosis due to oral dryness. The third patient, a 79-year-old woman, was suffering from severe dry mouth, associated with Sjögren's syndrome. Due to the ruinous condition of her teeth and extreme dry mouth, the decision was made to remove the remaining dentition and insert implant-retained dentures.
34880942 Tocilizumab drug levels during pregnancy and lactation: A woman who discontinued tocilizum 2021 Dec The demand for tocilizumab is increasing in women who wish to bear children and who have active rheumatoid arthritis. Described here is a woman with rheumatoid arthritis who discontinued her tocilizumab therapy at the end of the first trimester and resumed it after delivery and where tocilizumab levels in maternal serum, infant serum, and the breast milk were measured. Tocilizumab was not detected in maternal serum just before delivery, or in umbilical cord blood or infant serum after birth. Tocilizumab levels in colostrum after intravenous injection were 0.57% of those in serum. Tocilizumab treatment in the first trimester was not associated with a significant drug level in the fetus at delivery and no fetal complications were noted .
33553167 Regulatory Role of the RNA N(6)-Methyladenosine Modification in Immunoregulatory Cells and 2020 Rheumatoid arthritis (RA) is a systemic autoimmune disease for which the etiology has not been fully elucidated. Previous studies have shown that the development of RA has genetic and epigenetic components. As one of the most highly abundant RNA modifications, the N(6)-methyladenosine (m(6)A) modification is necessary for the biogenesis and functioning of RNA, and modification aberrancies are associated with various diseases. However, the specific functions of m(6)A in the cellular processes of RA remain unclear. Recent studies have revealed the relationship between m(6)A modification and immune cells associated with RA. Therefore, in this review, we focused on discussing the functions of m(6)A modification in the regulation of immune cells and immune-related bone homeostasis associated with RA. In addition, to gain a better understanding of the progress in this field of study and provide the proper direction and suggestions for further study, clinical application studies of m(6)A modification were also summarized.