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ID PMID Title PublicationDate abstract
35646651 Intersection Between Large Granular Lymphocyte Leukemia and Rheumatoid Arthritis. 2022 Large granular lymphocyte (LGL) leukemia, a rare hematologic malignancy, has long been associated with rheumatoid arthritis (RA), and the diseases share numerous common features. This review aims to outline the parallels and comparisons between the diseases as well as discuss the potential mechanisms for the relationship between LGL leukemia and RA. RA alone and in conjunction with LGL leukemia exhibits cytotoxic T-cell (CTL) expansions, HLA-DR4 enrichment, RA-associated autoantibodies, female bias, and unknown antigen specificity of associated T-cell expansions. Three possible mechanistic links between the pathogenesis of LGL leukemia and RA have been proposed, including LGL leukemia a) as a result of longstanding RA, b) as a consequence of RA treatment, or c) as a driver of RA. Several lines of evidence point towards LGL as a driver of RA. CTL involvement in RA pathogenesis is evidenced by citrullination and granzyme B cleavage that modifies the repertoire of self-protein antigens in target cells, particularly neutrophils, killed by the CTLs. Further investigations of the relationship between LGL leukemia and RA are warranted to better understand causal pathways and target antigens in order to improve the mechanistic understanding and to devise targeted therapeutic approaches for both disorders.
35096892 Anti-citrullinated Protein Antibody Generation, Pathogenesis, Clinical Application, and Pr 2021 Anti-citrullinated protein antibodies (ACPAs) are autoantibodies commonly observed in patients with rheumatoid arthritis (RA). Currently, most of the mechanisms of ACPA formation and bone destruction are well-understood, however, some unknown mechanisms still exist. There have been many new advances in ACPA-related clinical applications and targeted therapies. However, the existence of different ACPA subtypes is a limitation of targeted therapy. Herein, we present an overview of the process of ACPA generation, the underlying pathogenesis, and relevant clinical application and prospects.
35015417 Golimumab. 2022 Jan Golimumab is FDA approved for the treatment of moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PA), ankylosing spondylitis (AS), ulcerative colitis (UC), and polyarticular juvenile idiopathic arthritis (pcJIA). It is a human monoclonal antibody tumor necrosis factor-alpha (TNF-a) blocker, binding human TNF-a soluble and transmembrane structures and blocking its binding with the respective TNF-a receptors. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to interprofessional team members in the management of patients with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PA), ulcerative colitis (UC), and polyarticular course juvenile idiopathic arthritis (pcJIA) that is unresponsive to first-line therapy.
35348242 Metabolic characteristics and pharmacokinetic differences of Qiwei Tongbi oral liquid in r 2022 Mar 29 Qiwei Tongbi oral liquid (QWTB), a classical traditional Chinese medicine formula, is widely used to treat arthritis-related diseases in clinical practice. Currently, in vivo metabolic characteristics and pharmacokinetic studies are lacking. This study analyzed the prototype components of QWTB absorbed in the blood and their metabolic transformation process after intragastric administration and compared the differences in pharmacokinetic properties between healthy and rheumatoid arthritis model rats. In sum, 17 prototype components and 21 related metabolites were identified in the plasma and urine of the treated rats. Metabolites were derived from sinomenine and magnoflorine. Through systematic methodology verification, an accurate and stable detection method for sinomenine and magnoflorine in plasma samples was established and applied to pharmacokinetic research of QWTB. At the three dose levels, the AUC(0-∞) (area under the curve) of the two components showed a good positive correlation with the dose (R(2)  > 0.9). Compared with healthy rats, the T(max) , t(1/2z) , and AUC of sinomenine were markedly increased, and C(max) was decreased in rheumatoid arthritis model rats, indicating that the rate of absorption and elimination rate decreased, but the body exposure increased. However, there were no significant differences in the pharmacokinetic parameters of magnoflorine under healthy and pathological conditions. In summary, the main active ingredients of QWTB are sinomenine and magnoflorine, which exhibit linear kinetic characteristics within a set dose range, and the rheumatoid arthritis pathological state is more conducive to the absorption and efficacy of sinomenine. The results of this study demonstrate the rationality of the clinical application of the QWTB.
35168508 Assessment of Rheumatoid Hand Function as a Characteristic Feature of Rheumatoid Arthritis 2022 Feb 15 BACKGROUND: The hand is an excellent work tool that provides the functional ability to mechanical work. The hand is affected in rheumatoid arthritis (RA) patients, it is a significant problem in the functional sphere as a result of deformities, the grasping function limitation and muscle strength. OBJECTIVES: The aim of the study was the assessment of grip strength, endurance and manipulation abilities of rheumatoid hands with or without deformities treated with methotrexate (MTX) or MTX plus biologics (MTX+BIO). MATERIAL AND METHODS: The study involved 80 RA women, (40 received MTX+BIO, 40 MTX), treated at the Rheumatology Department of the Central Clinical Hospital of Interior Affairs in Warsaw. VAS-pain, DAS28, SDAI, HAQ, HAQ hands, estimation of hand grip strength, endurance, manipulation ability were analyzed. RESULTS: In group MTX+BIO values of DAS28 (3.7±1.3 vs 4.3±1.2, p=0.019), HAQ (0.72 ± 0.57 vs 1.08± 0.87, p=0.011) and HAQ-hand (0.85±0.65 vs. 1.19±0.68, p=0.024) were statistically lower than in MTX group. Hand deformations recorded in 35 (43.7%) cases, 16 (40%) in MTX group, 19 (47.5%) in MTX+BIO. Comparison of grip strength, endurance, manipulation ability showed better results in MTX+BIO group with deformities (significance level from 0.013 to 0.046) than in MTX group. Relative differences in hand function in MTX + BIO group ranged from 10.8% (maximal power grip strength) to 127.6% (minimal hand endurance), after disease duration adjustment - from 28.2% (maximal power grip strength) to 148.4% (minimal hand endurance). CONCLUSION: Measuring grip strength, hand endurance, manipulation abilities are useful in RA patients with hand deformities.
32491741 Sulfasalazine. 2022 Jan Sulfasalazine is a disease-modifying antirheumatic drug (DMARD) used in the treatment and management of autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease. This activity reviews the indications, contraindications, mode of action, adverse events, and other key elements of sulfasalazine therapy in the clinical setting as relates to the essential points needed by members of an interprofessional team managing the care of patients with inflammatory bowel disease and rheumatoid arthritis and its related conditions and sequelae.
35549856 Scrutinizing the role of Genetically Modified Herbs (GMHs) in the Treatment of Various Dis 2022 May 12 BACKGROUND: Medicinal plants are being manipulated by the variety of methods with genes. Genetic engineering is the alteration of genetic material of an organism via biotechnology techniques. Wide range of genetically modified medicinal plants are diligently examined possessing therapeutic efficacy for the treatment of various diseases, like diabetes, cardiovascular diseases, rheumatoid arthritis, and cancer. OBJECTIVE: This review discloses the numerous genetically modified herbs employed in the treatment of diseases, such as diabetes, cardiovascular diseases, rheumatoid arthritis, and cancer. In addition, the review highlights the therapeutically active constituents present in these herbs, which are liable for their specific pharmacological action. METHODS: Several review, research papers, and patents highlighting the enormous aptitude of genetically modified herbs in the treatment of various diseases were collected from medical databases, and are exhaustively studied for writing this review paper. RESULTS: Due to rapid advancement in the phytochemical investigation of therapeutically active plants, and because of their potential to treat these disorders, they are being rapidly promoted and favoured nowadays. Moreover, a range of active constituents can be isolated from natural plants that can be employed in the treatment of various disorders, and due to their less toxicity they are preferred over synthetic products. CONCLUSION: Utilizing genetically modified herbs, like Azadirachta indica, Allium cepa, Acacia arabica, Allium sativum, and herbal formulations like flaxseed oil, green tea, and many more appear to be a pioneerstrategy in the therapy of these diseases, but still further investigation is required to overcome the negative outcomes of these herbs.
35249916 A Case of Pneumonia and Meningoencephalitis Due to Varicella-zoster Virus Reinfection and 2022 Mar 5 A 72-year-old woman with rheumatoid arthritis was treated with methotrexate (MTX) and iguratimod. Upon examination of a liver tumor, blisters due to varicella-zoster virus (VZV) infection were observed. Despite oral administration of valacyclovir, she developed varicella pneumonia and meningoencephalitis. A VZV antibody test revealed reinfection. The liver tumor shrank after discontinuance of MTX, and polymerase chain reaction revealed the reactivation of the Epstein-Barr virus (EBV). Therefore, we were unable to deny MTX-associated lymphoproliferative disorder (MTX-LPD). This is the first case of a complication of pneumonia and meningoencephalitis due to VZV reinfection and EBV reactivation.
35597122 Emerging therapeutic potential of regulatory T (Treg) cells for rheumatoid arthritis: New 2022 May 19 Rheumatoid arthritis (RA) is an autoimmune-related disorder characterized by chronic inflammation. Although the etiopathogenesis of RA still remains to be clarified, it is supposed that the breakdown of immune self-tolerance may contribute to the development of RA. Thus, restoring of immune tolerance at the site of inflammation is the ultimate goal of RA treatment. Regulatory T cells (Treg cells) are the main suppressive cells that maintain tolerance and inhibit immunity against auto-antigen. Of note, recent studies demonstrated the efficacy of adoptive transfer of Treg cells in the modulation of the unwanted immune response, which makes them an ideal candidate to maintain immune homeostasis and restore antigen-specific tolerance in the case of RA and other autoimmune diseases. This review intends to submit recent finding of Treg cells-based therapies in RA with a focus on strategies applied to improve the therapeutic value of Treg cells to restore immune tolerance.
35071501 Hepatitis B virus reactivation in rheumatoid arthritis. 2022 Jan 7 Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovitis, which can cause cartilage and bone damage as well as functional limitations. Disease-modifying anti-rheumatic drugs have significantly improved the prognosis of RA patients. However, people with RA, when combined with hepatitis B virus (HBV) infection, may experience reactivation of HBV during treatment with anti-rheumatic drugs. The outcome of HBV reactivation (HBVr) varies from liver inflammation to liver failure, while insufficient HBV screening in RA patients has been reported in various countries. Therefore, it is necessary to identify patients at high risk before starting immunosuppressive therapy. The immune response plays an important role in anti-HBV infection. However, most anti-rheumatic drugs exert an inhibitory effect on the body's immune system, resulting in HBVr. Therefore, it is necessary to conduct a comprehensive evaluation based on host factors, viral factors, and drug factors. In this paper, we summarize the mechanism of HBVr, the risk of HBVr caused by anti-rheumatic drugs, and the appropriate diagnosis and treatment process for RA patients so that clinicians can have a more comprehensive understanding of HBVr in RA patients.
35601818 Periodontitis in First Degree-Relatives of Individuals With Rheumatoid Arthritis: A Short 2022 Periodontal disease (PD) and rheumatoid arthritis (RA) are chronic inflammatory diseases with a bi-directional relationship. Both share common genetic and environmental risk factors and result in the progressive destruction of bone and connective tissue. First degree relatives of patients with RA (FDR-RA) are one of the at-risk populations for RA. The etiopathogenic mechanisms of their susceptibility are currently being explored, focusing mostly on the role of anti-cyclic citrullinated protein/ peptide antibodies (ACPA) in triggering RA. Oral microbiota and their relation with oral health has been suggested as a factor influencing the risk of the FDR-RA developing RA. In particular, compromised periodontal status often correlates with ACPA seropositivity in FDR-RA. The presence of periodontal pathogens such as Porphyromonas gingivalis, in oral microbiota has been proposed to increase the risk of developing RA through its uniquely expressed peptidyl arginine deiminase (PPAD), capable of citrullinating both host and bacterial peptides. Aggregatibacter actinomycetemcomitans and its leukotoxin A (LtxA), also induces hypercitrullination in host neutrophils. Common risk factors of periodontitis and RA such as genetic predisposition, smoking, higher local and systemic inflammatory burden, are discussed in the literature. Based on those mechanisms periodontal disease seems to be presented as one of the factors triggering RA in FDR-RA. Larger studies evaluating all the potential mechanisms linking RA and periodontitis are needed in FDR-RA to confirm that periodontal disease should be considered in the screening of FDR-RA.
35165740 Seasonal Exacerbation of Rheumatoid Arthritis Detected by Big Claims Data Analysis: A Retr 2022 Feb 15 OBJECTIVES: The objective of the study was to determine the seasonal changes in the initiation of biological disease-modifying antirheumatic drugs (bDMARDs) and methotrexate (MTX) using big claims data. METHODS: We counted the monthly number of initial administrations of each bDMARD and MTX in patients with rheumatoid arthritis (RA) between April 2010 and March 2017. Data were collected from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). This database covers more than 95% of Japanese citizens. Seasonal changes in the number of initiations were determined. Patient claims were also classified according to drugs, districts, gender and ages. RESULTS: The initiation of bDMARDs and MTX administration varied according to the season in a sine curve shape, with the highest numbers in May to July and the lowest numbers in November to January. The same changing pattern was observed among each bDMARD, district, gender and age groups particularly when the number was on the higher side. CONCLUSION: We noted an apparent seasonal change in the number of bDMARDs initiated, with a peak during spring, suggesting an exacerbation of RA in the spring in Japan. These changes are overlooked in daily practice and are only visible using big data.
35640001 A Retrospective, Longitudinal Study of Rheumatoid Arthritis Treatment Patterns with Janus 2022 May 27 OBJECTIVES: There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis (RA) treatment in Japan. The aim of this study was to identify disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan. METHODS: This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with RA diagnosis were enrolled 2016-2019, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic (cs)DMARDs; tumor necrosis factor alpha (TNFα) inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis. RESULTS: Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other csDMARDs, and TNFα inhibitors. The total number of JAKi prescriptions increased approximately eight-fold during 2016-2019. Most (61.1%) patients who received JAKis had prior MTX or TNFα inhibitor treatment. JAKi treatment duration was longer than for biologics and other csDMARDs, and comparable to that of MTX. CONCLUSIONS: The sequence of drug class prescriptions for RA in Japan during 2016-2019 followed clinical guidelines. Over this period, JAKis were increasingly used as second-line treatment following MTX.
35597527 An attempt to unravel the association of TAGAP gene SNPs with rheumatoid arthritis in the 2022 May 18 Rheumatoid arthritis (RA) is an inflammatory disease that causes inflammation of the synovium, cartilage, and deformity of the bones. Single nucleotide polymorphism (SNPs) at 5'UTR rs1738074 (A/G) and a novel candidate non-synonymous single nucleotide polymorphism (nsSNP) rs759674898 (G/A) of TAGAP gene were studied for its association with RA in the Indian population. Real-time PCR coupled with High Resolution Melting analysis technique was employed to detect SNPs. The resulting outcomes were confirmed using the "traditional" Sanger's sequencing method. From this study, we identified that rs1738074 SNP was associated with RA. The odds ratio (OR) obtained for the AG genotype was 3.3379 (Confidence Interval (C.I) 1.7881 to 6.2350); for AA genotype 0.5510 (C.I 0.3043 to 0.9979) and GG genotype 0.5609 (CI 0.3062 to 1.0275). The study also confirmed that AG heterozygous condition had more significant association with RA than AA and GG genotypes. The obtained relative risk (RR) for the AA genotype was 0.676; for AG genotype (RR = 2.253) and GG genotype (RR = 0.6741). The novel candidate nsSNP rs759674898 had only the G allele, and the A allele was not detected in the population studied. In conclusion, this study emphasizes that the rs1738074 SNP in the TAGAP gene's 5'UTR is substantially linked to RA in the Indian population.
35257093 Metabolites and metabolic pathways associated with rheumatoid arthritis and systemic lupus 2022 Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases that result from the combined influence of genetic and environmental factors that promotes the loss of tolerance to cellular components. The complexity of these diseases converts them into a major challenge at the diagnostic and treatment level. Therefore, it is convenient to implement the use of tools for a better understanding of the physiopathology of these diseases to propose reliable biomarkers. The "omics" disciplines like metabolomics and lipidomics allow to study RA and SLE in a higher degree of detail since they evaluate the metabolites and metabolic pathways involved in disease pathogenesis. This review has compiled the information of metabolomics and lipidomics studies where samples obtained from RA and SLE patients were evaluated to find the metabolites and pathways differences between patients and healthy controls. In both diseases, there is a decrease in several amino acids and oxidative stress-related metabolites like glutathione. These findings may be useful for functional metabolomics studies aiming to reprogram the metabolism in a disease setting to recover normal immune cell homeostasis and function.
35467469 Macrophage targeted triptolide micelles capable of cGAS-STING pathway inhibition for rheum 2022 May 3 The abundant M1 macrophages in the joint synovium were the main factors that exacerbate rheumatoid arthritis (RA) by secreting various types of inflammatory cytokines. Here, we note that cGAS-STING, an important pro-inflammatory pathway, was significantly up-regulated in RA, enabling it be the potential target for RA therapy. Therefore, in this work, we developed M1 macrophages targeted micelles capable of cGAS-STING pathway inhibition for the smart treatment of RA. The folic acid (FA) and lauric acid (LA) were modified on dextran to obtain an amphiphilic polymer (FDL). Then, FDL was subsequently applied to encapsulate triptolide (TP) to form FDL@TP nanomicelles. The FDL@TP could target the joint and enhance the cell uptake of TP by M1 macrophages (overexpressing folate receptor-β), which also reduced the side effects of TP on normal tissues. In M1 macrophages, the released TP, acted as an anti-inflammatory and immunosuppressant, obviously down-regulated the expressions of cGAS and STING protein, and thus reduced the secretion of TNF-α, IL-1β and IL-6. Importantly, compared with the same dose of free TP, FDL@TP could significantly enhance the anti-inflammatory effect. Therefore, FDL@TP nanomicelles were believed to be superior candidates for the clinical treatment of RA.
33337810 Hemophagocytic Lymphohistiocytosis Hospitalizations in Adults and Its Association With Rhe 2022 Jan 1 OBJECTIVE: Hemophagocytic lymphohistiocytosis (HLH) is a rare potentially fatal multisystem inflammatory condition that is often triggered by an underlying medical condition. Epidemiologic data of HLH in adults with rheumatologic diseases are limited. The aim of our study was to characterize HLH hospitalizations in the US adult population with a special focus on patients with concomitant rheumatologic diseases. METHODS: We conducted a medical records review of hospitalizations in the United States during 2016 and 2017 with a diagnosis of HLH. Hospitalizations were selected from the National Inpatient Sample. International Classification of Diseases, Tenth Revision codes were used to identify rheumatologic diseases. A multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORadj) for the association of HLH and rheumatologic diseases. RESULTS: Seven hundred fifty hospitalizations had a principal billing diagnosis of HLH. The median age of our study population was 47.5 years, and males made up 55% of the population. Overall mortality was 17%, and the median length of stay was 12 days. Twenty-five percent of the HLH cases had a concomitant rheumatologic diagnosis. Multivariate logistic regression analysis showed systemic lupus erythematosus (SLE) with nephritis (ORadj, 5.7), SLE without nephritis (ORadj, 9.2), adult-onset Still disease (ORadj, 338.9), and ankylosing spondylitis (ORadj, 10.7) were significantly associated with HLH. CONCLUSIONS: This analysis represents the largest sample to date to assess HLH hospitalizations. Our study showed that SLE, adult-onset Still disease, and ankylosing spondylitis were strongly associated with HLH.
35321971 Inhibition of Kruppel-like factor 7 attenuates cell proliferation and inflammation of fibr 2022 Mar 23 Rheumatoid arthritis (RA) is an autoimmune disease, which can lead to joint inflammation and progressive joint destruction. Kruppel-like factor 7 (KLF7) is the member of KLF family and plays an important role in multiple biological progresses. However, its precise roles in RA have not been described. Present study aimed to investigate the role of KLF7 in RA-fibroblast-like synoviocytes (FLSs). Data showed that KLF7 expression was obviously upregulated in synovial tissues of rats with adjuvant-induced arthritis. Functional studies demonstrated that the loss of KLF7 may suppress cell proliferation and the expression of pro-inflammatory factors (interleukin (IL)-6, IL-1β, IL-17A) and matrix metalloproteinase (MMP-1, MMP-3, MMP-13) in FLSs through the inhibition of phosphorylation of NF-κB p65 and JNK. We further showed that miR-9a-5p specifically interacts with KLF7 to negatively regulate the expression of KLF7 in RA-FLSs. Taken together, our results demonstrated that KLF7 which targeted by miR-9a-5p might participate in the pathogenesis of RA by promoting cell proliferation, pro-inflammatory cytokine release and MMP expression through the activation of NF-κB and JNK pathways in RA-FLSs. Hence, KLF7 could be a novel target for RA therapy.
35282742 A pH-Driven indomethacin-loaded nanomedicine for effective rheumatoid arthritis therapy by 2022 Mar 28 Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by inflammatory micro-environments in the joints. Indomethacin (IND), a conventional nonsteroidal anti-inflammatory drug (NSAID), has been used for the therapy of RA. However, the poor solubility and serious side effects of oral administration of IND significantly limit its efficacy. In this study, we have synthesized biomimetic IND-loaded Prussian blue (PB) nanoparticles (IND@PB@M@HA) with hyaluronic acid (HA) modification for increasing the solubility and targeting the ability of IND to the inflamed joints. The application of hybrid cell membranes on the NPs endowed immune escape of IND@PB@M@HA NPs, which accordingly extended the circulation time in the blood. In vitro assay demonstrated that the combination of nanomedicine and photothermal therapy produced a powerful anti-inflammatory effect by reducing the levels of inflammatory factors and cell viability of activated macrophages and NPs possessed obvious pH-responsiveness. In vivo assay demonstrated that the nanomedicine for synergistic photothermal therapy exhibited desirable pharmacodynamics and pharmacokinetic properties at ultra-low drug dosage in a rat model of adjuvant-induced arthritis, which was confirmed by inflammatory suppression, bone erosion remission, and negligible adverse effects. In summary, the proposed nanomedicine has the potential role for targeted anti-inflammatory therapy of RA.
35330498 Focus on Sex and Gender: What We Need to Know in the Management of Rheumatoid Arthritis. 2022 Mar 20 Rheumatoid arthritis (RA) is a chronic inflammatory disease, affecting mostly women with a female/male ratio of 3:1. It is characterized by symmetrical polyarthritis, leading to progressive joint damage. Sex differences have been reported in terms of disease course and characteristics, influencing patients reported outcome measures (PROMs) and pain perception, ultimately leading to male-female disparities in treatment response. Notwithstanding, sex and gender discrepancies are still under-reported in clinical trials. Therefore, there is a consistent need for a precise reference of sex and gender issues in RA studies to improve treat-to-target achievement. This narrative review explores the above-mentioned aspects of RA disease, discussing the latest core principles of RA recommendations, from safety issues to early arthritis concept and management, treat-to-target and difficult-to-treat notions, up to the most recent debate on vaccination. Our final purpose is to evaluate how sex and gender can impact current management guidelines and how this issue can be integrated for effective disease control.