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

ID PMID Title PublicationDate abstract
33902919 [Rheumatic immune adverse events related to immune checkpoint inhibitors-(IrAEs related to 2021 Jun New anti-cancer therapeutics have been developed in the recent years and dramatically change prognosis and patient management. Either used alone or in combination, immune checkpoint inhibitors (ICI), such as anti-CTLA-4 and anti-PD1/PD-(L)1, act by removing T-cell inhibition to enhance their antitumor response. This change in therapeutic targets leads to a break in immune-tolerance and a unique toxicity profile resulting in immune complications. These side effects, called Immune-Related Adverse Events (IrAEs), can affect all organs, with a wide range of clinical and biological presentations and severity. Various rheumatic and musculoskeletal manifestations have been reported in the literature, ranging from mild arthralgia, polymyalgia rheumatica, to genuine serodefined rheumatoid arthritis and myositis. Tolerance studies suggest some correlations between IrAEs occurrence and tumor response. Assessment of patient musculoskeletal status prior to the start of the ICI is warranted. Management of rheumatic IrAEs does not usually request ICI discontinuation, exception for myositis or very severe forms where it should be discussed. Treatment relies on non-steroidal anti-inflammatory drugs (NSAIDs) or low dose glucocortioids (<20mg per day). Dose should be adjusted according to severity. The use of disease modifying anti-rheumatic drugs (DMARDs), either conventional and/or biological should be very cautious and result from a shared decision between oncologist and rheumatologist to best manage dysimmunitary complications without hampering the antitumor efficacy of ICI.
33479021 Older age, comorbidity, glucocorticoid use and disease activity are risk factors for COVID 2021 Jan INTRODUCTION: Whether patients with inflammatory rheumatic and musculoskeletal diseases (RMD) are at higher risk to develop severe courses of COVID-19 has not been fully elucidated. Aim of this analysis was to describe patients with RMD according to their COVID-19 severity and to identify risk factors for hospitalisation. METHODS: Patients with RMD with PCR confirmed SARS-CoV-2 infection reported to the German COVID-19 registry from 30 March to 1 November 2020 were evaluated. Multivariable logistic regression was used to estimate ORs for hospitalisation due to COVID-19. RESULTS: Data from 468 patients with RMD with SARS-CoV-2 infection were reported. Most frequent diagnosis was rheumatoid arthritis, RA (48%). 29% of the patients were hospitalised, 5.5% needed ventilation. 19 patients died. Multivariable analysis showed that age >65 years (OR 2.24; 95% CI 1.12 to 4.47), but even more>75 years (OR 3.94; 95% CI 1.86 to 8.32), cardiovascular disease (CVD; OR 3.36; 95% CI 1.5 to 7.55), interstitial lung disease/chronic obstructive pulmonary disease (ILD/COPD) (OR 2.79; 95% CI 1.2 to 6.49), chronic kidney disease (OR 2.96; 95% CI 1.16 to 7.5), moderate/high RMD disease activity (OR 1.96; 95% CI 1.02 to 3.76) and treatment with glucocorticoids (GCs) in dosages >5 mg/day (OR 3.67; 95% CI 1.49 to 9.05) were associated with higher odds of hospitalisation. Spondyloarthritis patients showed a smaller risk of hospitalisation compared with RA (OR 0.46; 95% CI 0.23 to 0.91). CONCLUSION: Age was a major risk factor for hospitalisation as well as comorbidities such as CVD, ILD/COPD, chronic kidney disease and current or prior treatment with GCs. Moderate to high RMD disease activity was also an independent risk factor for hospitalisation, underlining the importance of continuing adequate RMD treatment during the pandemic.
33727111 Effects of rhizome of Atractylodes koreana (Nakai) Kitam on intestinal flora and metabolit 2021 Dec 5 ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodis rhizoma in Chinese Pharmacopoeia are Atractylodes lancea (Thunb.) DC and Atractylodes chinensis (DC.) Koidz. Atractylodes koreana (Nakai) Kitam has not been included in Chinese Pharmacopoeia, however, in the 'dictionary of traditional Chinese medicine', Atractylodes koreana (Nakai) Kitam is often used as Atractylodis rhizoma in the north of China. According to 'Chinese traditional medicine resources', Atractylodes koreana (Nakai) Kitam has the function of drying dampness and strengthening the spleen, dispelling wind and eliminating dampness. AIM OF THIS STUDY: The study was to explore the effect and mechanism of Atractylodes koreana (Nakai) Kitam on rheumatoid arthritis(RA) through intestinal flora and its metabolites(short chain fatty acids). MATERIALS AND METHODS: 36 male SD rats were randomly divided into 6 groups. The Freund's complete adjuvant method was used to reproduce RA model. The contents of inflammatory factors in the plasma of rats were monitored by ELISA method. The pathological changes of synovium were observed. 16SrDNA high-throughput sequence method was used to study the composition and structure of intestinal microflora in each group of rats. Gas Chromatography and Mass Spectrum(GC-MS) method was used to determine the content of short chain fatty acids(SCFAs) in colon of rats of each group. RESULTS: After oral administration of Atractylodes koreana (Nakai) Kitam, the synovial infiltration and vascular proliferation in RA rats were alleviated, the level of TNF - α, IL-1, IL-1 β, IL-2, IL-6, hs-CRP in the plasma of RA rats were declined. RA could cause the disturbance of intestinal flora and SCFAs, Atractylodes koreana (Nakai) Kitam could regulate 8 genera of intestinal flora and improve the disorder of SCFAs. CONCLUSIONS: Atractylodes koreana (Nakai) Kitam has a therapeutic effect on RA, the therapeutic mechanism may be related to down-regulating inflammatory factors and improving the imbalance of intestinal flora and SCFAs.
33411638 Exercise protects against cardiac and skeletal muscle dysfunction in a mouse model of infl 2021 Mar 1 Rheumatoid arthritis (RA) is a systemic inflammatory arthritis impacting primarily joints and cardiac and skeletal muscle. RA's distinct impact on cardiac and skeletal muscle tissue is suggested by studies showing that new RA pharmacologic agents strongly improve joint inflammation, but have little impact on RA-associated mortality, cardiovascular disease, and sarcopenia. Thus, the objective is to understand the distinct effects of RA on cardiac and skeletal muscle, and to therapeutically target these tissues through endurance-based exercise as a way to improve RA mortality and morbidity. We utilize the well-characterized RA mouse model, the K/BxN mouse, to investigate cardiac and skeletal muscle pathologies, including the use of wheel-running exercise to mitigate these pathologies. Strikingly, we found that K/BxN mice, like patients with RA, also exhibit both cardiac and skeletal muscle myopathies that were correlated with circulating IL-6 levels. Three months of wheel-running exercise significantly improved K/BxN joint swelling and reduced systemic IL-6 concentrations. Importantly, there were morphological, gene expression, and functional improvements in both the skeletal muscle and cardiac myopathies with exercise. The K/BxN mouse model of RA recapitulated important RA clinical comorbidities, including altered joint, cardiac and skeletal muscle function. These morphological, molecular, and functional alterations were mitigated with regular exercise, thus suggesting exercise as a potential therapeutic intervention to lessen disease activity in the joint and the peripheral tissues, including the heart and skeletal muscle.NEW & NOTEWORTHY RA, even when controlled, is associated with skeletal muscle weakness and greater risk of cardiovascular disease (CVD). Using exercise as a therapeutic against, the progression of RA is often avoided due to fear of worsening RA pathology. We introduce the K/BxN mouse as an RA model to study both myocardial and skeletal muscle dysfunction. We show that endurance exercise can improve joint, cardiac, and skeletal muscle function in K/BxN mice, suggesting exercise may be beneficial for patients with RA.
34045525 Clinical factors associated with discontinuation of ts/bDMARDs in rheumatic patients from 2021 May 27 Biologic and targeted synthetic disease-modifying antirheumatic drugs (ts/bDMARDs) play a pivotal role in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Persistence of therapy provides an index of a drug's overall effectiveness. The objective of the study was to identify factors associated with discontinuation of ts/bDMARDs in a real-world dataset. The study population comprised patients diagnosed with RA, PsA, and AS included in the BIOBADASER registry for whom follow-up data were available until November 2019. Patient features and treatment data were included in the analysis. The Kaplan-Meier method was used to study survival of the different drugs according to the reason for discontinuation. Factors associated with discontinuation were studied using Cox regression models and bivariate and multivariate analyses. P values of less than 0.05 were regarded as statistically significant. The study population comprised 4,752 patients who received a total of 8,377 drugs, of which 4,411 (52.65%) were discontinued. The Kaplan-Meier curves showed that survival for first-line treatment was greater in all 3 groups (p < 0.001). Patients with RA had a greater risk of discontinuation if they were younger (HR, 0.99; 95% CI 0.99-1.00), if they were receiving anti-TNFα agents (HR, 0.61; 95% CI 0.54-0.70), and if they had more comorbid conditions (HR, 1.09; 95% CI 1.00-1.17). Patients with PsA had a higher risk if they were women (HR, 1.36; 95% CI 1.15-1.62) and if they were receiving other ts/bDMARDs (HR, 1.29; 95% CI 1.05-1.59). In patients with AS, risk increased with age (HR, 1.01; 95% CI 1.00-1.02), as did the number of comorbid conditions (HR, 1.27; 95% CI 1.12-1.45). The factors that most affected discontinuation of ts/bDMARDs were line of treatment, age, type of drug, sex, comorbidity and the year of initiation of treatment. The association with these factors differed with each disease, except for first-line treatment, which was associated with a lower risk of discontinuation in all 3 diseases.
32596727 Comparable or higher prevalence of comorbidities in antiphospholipid syndrome vs rheumatoi 2021 Jan 5 OBJECTIVES: Evidence on comorbidity prevalence in antiphospholipid syndrome (APS) and its difference from high comorbidity burden rheumatic diseases is limited. Herein, we compare multiple comorbidities between APS and RA. METHODS: A total of 326 patients from the Greek APS registry [237 women, mean age 48.7 (13.4) years, 161 primary APS (PAPS), 165 SLE-APS] were age/sex matched (1:2 ratio) with 652 patients from a Greek multicentre RA cohort of 3115 patients. Prevalence of cardiovascular (CV) risk factors, stroke, coronary artery disease (CAD), osteoporosis, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), depression and neoplasms were compared between APS and RA patients using multivariate regression analysis. RESULTS: Ηyperlipidemia and obesity (ΒΜΙ ≥ 30 kg/m2) were comparable while hypertension, smoking, stroke and CAD were more prevalent in APS compared with RA patients. Osteoporosis and depression were more frequent in APS, while DM, COPD and neoplasms did not differ between the two groups. Comparison of APS subgroups to 1:2 matched RA patients revealed that smoking and stroke were more prevalent in both PAPS and SLE-APS vs RA. Hypertension, CAD and osteoporosis were more frequent only in SLE-APS vs RA, whereas DM was less prevalent in PAPS vs RA. Hyperlipidaemia was independently associated with CV events (combined stroke and CAD) in PAPS and SLE-APS, while CS duration was associated with osteoporosis in SLE-APS. CONCLUSION: Comorbidity burden in APS (PAPS and SLE-APS) is comparable or higher than that in RA, entailing a high level of diligence for CV risk prevention, awareness for depression and CS exposure minimization.
34975889 Antcin K Inhibits TNF-α, IL-1β and IL-8 Expression in Synovial Fibroblasts and Ameliorat 2021 Extracts from Taiwan's traditional medicinal mushroom, Antrodia cinnamomea, exhibit anti-inflammatory activities in cellular and preclinical studies. However, this paper is the first to report that Antcin K, a triterpenoid isolated from A. cinnamomea, inhibits proinflammatory cytokine production in human rheumatoid synovial fibroblasts (RASFs), which are major players in rheumatoid arthritis (RA) disease. In our analysis of the mechanism of action, Antcin K inhibited the expression of three cytokines (tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β] and IL-8) in human RASFs; cytokines that are crucial to RA synovial inflammation. Notably, incubation of RASFs with Antcin K reduced the phosphorylation of the focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and nuclear factor-κB (NF-κB) signaling cascades, all of which promote cytokine production in RA. Intraperitoneal injections of Antcin K (10 mg/kg or 30 mg/kg) attenuated paw swelling, cartilage degradation and bone erosion, and decreased serum levels of TNF-α, IL-1β, IL-8 in collagen-induced arthritis (CIA) mice; in further experiments, IL-6 levels were similarly reduced. The inhibitory effects of Antcin K upon TNF-α, IL-1β and IL-8 expression in human RASFs was achieved through the downregulation of the FAK, PI3K, AKT and NF-κB signaling cascades. Our data support clinical investigations using Antcin K in RA disease.
34215479 [Algorithms to identify chronic inflammatory rheumatism and psoriasis in medico-administra 2021 Aug BACKGROUND: We aimed to describe and discuss the algorithms used to identify chronic inflammatory rheumatisms and psoriasis in medico-administrative databases. METHODS: We performed a literature review on the Medline database of articles published up to 31 January 2018. Our inclusion criteria were: original articles using medico-administrative databases in accordance with the International Classification of Diseases, version 10 (ICD-10) and concerning rheumatoid arthritis (RA) or ankylosing spondylitis (AS) or psoriatic arthritis (PsoA) or Psoriasis (Pso). Our exclusion criteria were: letters to the editor, commentaries on published articles, studies using codes other than those of the ICD or a previous version. RESULTS: Out of the 590 articles identified, 37 studies were included. Concerning RA (n=10), all studies used the M05 code, associated with the M06 code in six studies. The remaining four studies specifically targeted codes M06.0, M06.2, M06.3, M06.8, M06.9, and two of them also used code M12.3. For AS (n=8), 7 studies used the M45 code, while only one study used M45.9, M46.1 or M46.8. For Pso (n=17), all studies used the L40 code and/or at least two dispensations of vitamin D. Concerning PsoA (n=13), all studies used the same codes: M07.0, M07.1, M07.2, M07.3. CONCLUSION: We recommend using codes M05 and M06 rather than M06.1 and M06.4 for RA, M45 for AS, the algorithm L40 and/or two dispensations of topical vitamin D for psoriasis, and codes M070 to M073 to identify PsoA patients in medico-administrative databases.
33759334 4-Phenylbutyric acid, a potent endoplasmic reticulum stress inhibitor, attenuates the seve 2021 Jul 4-Phenylbutyric acid (4-PBA) exerts potent pharmacological effects, including anti-inflammatory properties, via inhibition of endoplasmic reticulum (ER) stress. However, it is not known whether 4-PBA attenuates the severity of rheumatoid arthritis. The present study aimed to determine whether the inhibition of ER stress by 4-PBA ameliorated experimentally induced arthritis. The proliferation of synovial fibroblasts (SFs) and expression of matrix metalloproteinases (MMPs) were evaluated in the presence of interleukin (IL)-1β with or without 4-PBA. The effect of 4-PBA on the phosphorylation of Mitogen-activated protein kinase (MAPK) and the activation of Nuclear factor-κB (NF-κB) in IL-1β-stimulated SFs was assessed. In an in vivo study, the effects of 4-PBA were investigated using DBA/1 mice with collagen-induced arthritis (CIA). Clinical, histological, and serological assessments of CIA treated with 4-PBA were performed to determine the therapeutic effect of 4-PBA. In vitro, 4-PBA inhibited the proliferation and expression of IL-1β-stimulated SFs and MMP-1 and MMP-3 through the suppression of both the phosphorylation of MAPKs and NF-κB in IL-1β-stimulated SFs. The 4-PBA treatment markedly attenuated the severity of arthritis in CIA mice. The 4-PBA treatment ameliorated joint swelling and the degree of bone erosion and destruction and decreased the level of inflammatory cytokines and MMP-3 and Cox-2. Furthermore, remarkable improvements in histopathological findings occurred in 4-PBA-treated mice. These findings suggested that 4-PBA could attenuate the severity of arthritis in CIA mice by partially blocking the phosphorylation of MAPKs and the activation of NF-κB in SFs. Thus, through the inhibition of ER stress, 4-PBA may be a potent agent for the treatment of RA.
34924813 Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediate 2021 Ellagic acid (EA) was reported to play protective roles in rheumatoid arthritis (RA). It was found that the level of metastasis-associated gene 1 (MTA1)/histone deacetylase 1 (HDAC1) protein complex was downregulated by polyphenols in several human disorders. Notably, inhibition of MTA1 or HDAC1 has anti-inflammatory effects on RA. Therefore, our study is aimed at investigating whether EA prevents RA progression through regulating the MTA1/HDAC1 complex. Herein, the human fibroblast-like synoviocyte (FLS) cell line MH7A was treated with TNF-α to induce an inflammation model in vitro and then incubated with different concentrations of EA. Western blot analysis showed that EA reduced MTA1 expression in a dose-dependent manner in MH7A cells. Then, TNF-α-treated MH7A cells were incubated with EA alone or together with MTA1 overexpression plasmid (pcDNA-MTA1), and we found that EA inhibited proliferation, inflammation cytokine levels, and oxidative stress marker protein levels and promoted apoptosis in MH7A cells, while MTA1 overexpression abolished these effects. Moreover, coimmunoprecipitation assay verified the interaction between MTA1 and HDAC1. EA downregulated the MTA1/HDAC1 complex in MH7A cells. MTA1 knockdown inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells, while HDAC1 overexpression reversed these effects. Moreover, chromatin immunoprecipitation assay indicated that EA inhibited HDAC1-mediated Nur77 deacetylation. Rescue experiments demonstrated that Nur77 knockdown reversed the effects of EA on MH7A cell biological behaviors. Additionally, EA treatment attenuated arthritis index, paw swelling, synovial hyperplasia, and inflammation in collagen-induced arthritis (CIA) rats. In conclusion, EA inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells and alleviated the severity of RA in CIA rats though downregulating MTA1/HDAC1 complex and promoting HDAC1 deacetylation-mediated Nur77 expression.
33470345 Nodular anterior scleritis associated with Berger's disease. 2021 Jan A 45-year-old female patient presented with a complaint of right eye redness and pain for 7 days. She was under investigation for urinary abnormalities and reported a previous history of recurrent oral ulcers and ocular hyperemia in both eyes. Best-corrected visual acuity was 20/30 and 20/20 in the right and left eyes, respectively. Slit-lamp biomicroscopy of the ocular surface of the right eye revealed nasal scleral hyperemia that persisted after instillation of topical phenylephrine 10%, reinforcing the diagnosis of anterior scleritis. Renal biopsy showed immunoglobulin A immune complexes and confirmed the suspected diagnosis of Berger's disease. Maintenance immunosuppressive therapy with azathioprine following a 6-month induction of remission with cyclophosphamide was necessary after pulse therapy with methylprednisolone. Scleritis is usually related to systemic autoimmune diseases, such as rheumatoid arthritis, and polyangiitis. Herein, we describe a rare case of unilateral anterior scleritis associated with Berger's disease.
33407267 Health system wide "big data" analysis of rheumatologic conditions and scleritis. 2021 Jan 6 BACKGROUND: The development of scleritis in the setting of autoimmune conditions has been well documented. Prior series have assessed the relationship between systemic autoimmune disorders and scleritis only in patients referred for rheumatologic or ocular inflammation. This can lead to a referral bias. We reviewed all charts within the electronic medical record (EMR) of a health system for patients with systemic autoimmune and scleritis diagnoses to determine the prevalence of both and which disorders had the highest relative risk of developing scleritis. METHODS: The EMR was searched for scleritis and systemic inflammatory diagnoses in the past medical history and diagnosis tabs, and for associated disease specific laboratory values. The intersection of scleritis and systemic inflammatory conditions was assessed through searching both SNOMED Clinical Terminology and ICD-10 codes for diagnoses. The prevalence of each autoimmune disorder, scleritis prevalence, the percentage of patients with an autoimmune condition having scleritis, the percentage of patients with scleritis having an autoimmune condition; the relative risk (RR) of scleritis patients having a specific autoimmune disorder were calculated. RESULTS: A total of 5.9 million charts were searched with autoimmune conditions identified in 148,993 patients. The most common autoimmune conditions overall were HLA-B27-associated diseases (n = 26,680; prevalence 0.45%); rheumatoid arthritis (RA)(N = 19,923; prevalence 0.34%). Conversely, 2702 patients were identified with scleritis (prevalence 0.05%), of which 31.4% had an associated autoimmune condition. Patients with RA represented the highest percentage of patients with an autoimmune condition having scleritis. Granulomatosis with polyangiitis (GPA) represented the highest the percentage of patients with scleritis having an autoimmune condition. Sjogrens was the third most common condition associated with scleritis- making up 4.5% of cases. An association with juvenile idiopathic arthritis (JIA) was seen in 0.3% of patients. CONCLUSIONS: While this is the largest retrospective review examining the association between autoimmune disease and scleritis, the findings are similar to prior studies with nearly a third of scleritis patients having an underlying autoimmune diagnosis. Limitations of the study included accurate chart coding; having laboratory results within the searchable EMR. Future research is needed to delineate associations of systemic disease with the anatomic location of scleritis using EMR.
34595805 Prevalence and clinical correlates of antinuclear antibody in patients with gastroparesis. 2022 May BACKGROUND: Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders. AIMS: 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA. METHODS: Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). RESULTS: Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), T1DM (16% of 162), T2DM (18% of 147), and postfundoplication (19% of 48 patients) gastroparesis. Among 536 patients with idiopathic gastroparesis, ANA titer 1:40-1:80 was seen in 33 (6%) patients, 1:160-1:320 in 36 (7%) patients, and ≥1:640 in 17 (3%) patients. Increasing ANA titer was associated with female gender (p = 0.05), Hispanic ethnicity (p = 0.02), comorbid rheumatoid arthritis (p = 0.02), systemic sclerosis (p = 0.004), and elevated ESR (p = 0.007). ANA positivity was associated with lower total GCSI (p = 0.007) and lower nausea/vomiting subscale (p = 0.0005), but not related to gastric emptying. CONCLUSIONS: The prevalence of a positive ANA in patients with gastroparesis was high at ~17% and did not differ significantly based on etiology. In idiopathic patients, ANA positivity was associated with rheumatoid arthritis, systemic sclerosis, and elevated ESR. ANA-positive gastroparesis represents a subset who often have other autoimmune symptoms or disorders, but less severe nausea and vomiting.
33984299 Losartan protects endothelium-dependent relaxation in vivo in a murine model of rheumatoid 2021 Aug 5 Angiotensin II-type 1 receptor stimulation is recognised to promote inflammation, a state central to the development and maintenance of rheumatoid arthritis. Herein we examined the use of losartan, an angiotensin II-type 1 receptor antagonist, on vascular reactivity, knee joint diameter and behavioural assessment of pain in a Freund's complete adjuvant (FCA) mouse model of joint inflammation. Monoarthritis was induced via FCA in the presence or absence of losartan with naive mice serving as controls. Knee joint swelling, joint pain (assessed by dynamic weight bearing of limb use), knee joint artery reactivity (assessed ex vivo) and blood perfusion of the knee joint (assessed in vivo) were determined. FCA mediated a significant increase in knee joint diameter and reduced weight-bearing (a surrogate for pain sensation) of the affected limb. Notably, these phenomena were substantially reduced when mice were prophylactically treated with losartan. Assessment of arterial relaxation and blood perfusion with acetylcholine stimulation revealed that FCA resulted in significant vascular dysfunction, which was resolved to naïve levels with losartan treatment. Through the actions of losartan, these findings indicate that the angiotensin II-type 1 receptor is a likely therapeutic target of importance in the development of the physical changes, pain sensation and vascular dysfunction found in inflammatory arthritis.
34635950 Beyond immunosuppressive effects: dual roles of myeloid-derived suppressor cells in bone-r 2021 Dec Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells (IMCs) with immunosuppressive functions, whereas IMCs originally differentiate into granulocytes, macrophages, and dendritic cells (DCs) to participate in innate immunity under steady-state conditions. At present, difficulties remain in identifying MDSCs due to lacking of specific biomarkers. To make identification of MDSCs accurately, it also needs to be determined whether having immunosuppressive functions. MDSCs play crucial roles in anti-tumor, angiogenesis, and metastasis. Meanwhile, MDSCs could make close interaction with osteoclasts, osteoblasts, chondrocytes, and other stromal cells within microenvironment of bone and joint, and thereby contributing to poor prognosis of bone-related diseases such as cancer-related bone metastasis, osteosarcoma (OS), rheumatoid arthritis (RA), osteoarthritis (OA), and orthopedic trauma. In addition, MDSCs have been shown to participate in the procedure of bone repair. In this review, we have summarized the function of MDSCs in cancer-related bone metastasis, the interaction with stromal cells within the bone microenvironment as well as joint microenvironment, and the critical role of MDSCs in bone repair. Besides, the promising value of MDSCs in the treatment for bone-related diseases is also well discussed.
34036103 Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expre 2021 OBJECTIVES: The aim of our study was to investigate the association of single-nucleotide polymorphism (SNP) and mRNA expression profile of single immunoglobulin IL-1-related receptor (SIGIRR) in rheumatoid arthritis (RA) in a Chinese population. METHODS: SIGIRR rs7396562 polymorphism was genotyped using TaqMan allelic discrimination assay in 517 RA patients and 601 healthy controls. Simultaneously, the SIGIRR mRNA expression levels of 79 RA patients and 76 healthy controls were examined by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The frequency of SIGIRR rs7396562 T allele was significantly higher in RA patients compared with healthy controls (T versus G: OR = 1.277, 95%CI = 1.079 - 1.511, P = 0.004). The TT genotype of SIGIRR rs7396562 was more frequent in RA patients than in healthy controls (OR = 1.547, 95%CI = 1.107 - 2.163, P = 0.011). Moreover, we also found a significant difference in the recessive model (TT versus TG+GG: OR = 1.439, 95%CI = 1.122 - 1.847, P = 0.004). However, no significant evidence was observed for the association of the SIGIRR rs7396562 with RA in dominant model (TT+TG versus GG: OR = 1.275, 95%CI = 0.947 - 1.717, P = 0.109). Further analysis showed no association between SIGIRR rs7396562 polymorphism and laboratory parameters of RA patients (all P > 0.05). The mRNA expression of SIGIRR was decreased in PBMCs of patients with RA when compared to healthy controls (Z = -2.459, P = 0.014). No significant differences in SIGIRR mRNA expression levels were observed in patients with RA with different genotypes (P = 0.280). CONCLUSIONS: Our findings demonstrated that the dysregulation of SIGIRR might be associated with the pathogenesis of RA, and SIGIRR rs7396562 polymorphism might contribute to RA susceptibility in the Chinese population.
34752070 Pterostilbene Coupled with Physical Exercise Effectively Mitigates Collagen-Induced Articu 2021 Nov 24 Studies have revealed that a novel anti-inflammatory mediator─maresin-1 (MaR1)─can reduce the level of inflammatory factors. There is evidence that physical exercise (PE) promotes the biosynthesis of MaR1, leading to the prevention of rheumatoid arthritis (RA). Previously, we have proven that resveratrol can mitigate the formation of RA. Pterostilbene (Pte) is an analogue of resveratrol, but it is around four times more bioavailable. Hence, we hypothesize that Pte could be more effective in preventing RA, in particular, when accompanied by moderate PE. Based on this hypothesis, we explored the preventive effect of Pte combined with PE on a bovine type II collagen (BIIC)-stimulated rat RA model and its underlying molecular mechanism. Compared with the BIIC-stimulated group, the serum content of MaR1 with continuous intervention of Pte plus PE for 8 weeks was significantly increased to 46.3 pg/mL from 7.2 pg/mL in BIIC-treated alone. Besides, the variation in the relative expression levels of p-NF-κB and p-Akt was reversed with the administration of Pte plus PE. More importantly, the in vitro results confirmed that the treatment of Pte plus MaR1 inhibited proliferation and apoptosis and promoted the autophagy of the interleukin (IL)-1β-stimulated primary rat synovial cells through the PI3K/Akt/NF-κB signal pathway. Collectively, the oral administration of Pte plus moderate PE helped to ameliorate the pathological process of RA by correcting the PI3K/Akt/NF-κB signal pathway.
33950230 The safety of JAK-1 inhibitors. 2021 May 5 As efficacy and safety data emerge, differences between JAK inhibitor subclasses are appearing. JAK1 selective drugs, upadacitinib and filgotinib, have broadly come with the same overarching safety recommendations as other immunosuppressive drugs for RA: caution is needed regarding infection risk; monitoring for laboratory abnormalities, including lipids and muscle enzymes, is indicated. A distinguishing feature of JAK inhibitors is a risk for zoster reactivation. Numerically, overall rates of serious infection are similar among JAK inhibitor classes. There are currently no signals for diverticular perforation. VTE incidence rates were similar across comparator groups for the JAK1 selective agents. These observations are not yet conclusive evidence for different safety profiles between JAK1 selective agents and other JAK inhibitors. Differences in study population, design, and concomitant steroid use are examples of potential confounders. It is too early to draw conclusions on long-term outcomes such as malignancy and cardiovascular risk. Post-marketing pharmacovigilance studies will be essential.
34753831 LncRNA MIR31HG is induced by tocilizumab and ameliorates rheumatoid arthritis fibroblast-l 2021 Nov 9 Fibroblast-like synoviocytes (FLS) obtained from the joint synovium of rheumatoid arthritis (RA) patients exhibit hyperplasia and aggressive inflammatory phenotypes. This study was designed to explore the anti-inflammatory mechanism of IL-6R inhibitor, tocilizumab, in FLS-mediated inflammation in RA from the perspective of non-coding RNAs (ncRNAs). To this end, we sorted primary FLS obtained from the synovium of patients with RA and cultured them in vitro. The cells were then treated with tocilizumab and subjected to lncRNA- and miRNA-seq to identify the ncRNAs regulated by tocilizumab treatment using bioinformatic analysis and experimental verification. Tocilizumab treatment enhanced the expression of lncRNA MIR31HG and reduced that of micoRNA-214 (miR-214). In addition, miR-214 activated the AKT signaling pathway by directly targeting MIR31HG and PTEN. In addition, the tocilizumab-MIR31HG-miR-214-PTEN-AKT axis regulated the proliferation, migration, and production of inflammatory molecules and matrix metalloproteinases (MMPs) in RA-FLS. Furthermore, co-culture experiments showed that this axis could inhibit the inflammatory phenotype of macrophages and protect chondrocytes. In summary, our study shows that tocilizumab suppresses RA-FLS inflammation by regulating the MIR31HG-miR-214-PTEN-AKT pathway, and presents new insights on RA pathogenesis and potential targets for RA therapy.
33479909 Regulatory B Cells in Experimental Mouse Models of Arthritis. 2021 Regulatory B cells (Breg) have been shown to have a role in the suppression of a wide variety of immune responses, yet they are deficient or defective in autoimmune diseases such as rheumatoid arthritis. For the study of autoimmune inflammation, experimental models of arthritis have acted as a valuable tool in understanding the development of Bregs and their role in maintaining immune homeostasis. In this chapter, we will focus on the study of transitional-2 marginal zone precursor (T2-MZP) Bregs in the context of two experimental arthritis models: antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA). We will specifically focus on how to induce arthritis, as well as on methods for the isolation and functional study of Bregs both in vitro and in vivo.