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ID PMID Title PublicationDate abstract
34759075 Clinical Characteristics of Japanese Patients with Elderly-Onset Adult-Onset Still's Disea 2021 Nov The aim of this study was to compare the characteristics of Japanese patients with elderly-onset Adult-onset Still's disease (AOSD) and those with younger-onset AOSD. Patients were classified into elderly-onset (≥ 65 years, n = 20) and younger-onset (< 65 years, n = 62) groups according to age at AOSD diagnosis. Analyses included the comparison of clinical features, treatments, and Pouchot and modified Pouchot (mPouchot) scores between the two groups. The frequencies of sore throat, lymphadenopathy, and splenomegaly were significantly lower in the elderly-onset group than in the younger-onset group (30.5% vs. 80.6%, p = 0.0004; 15.0% vs. 54.8%, p = 0.0019; 30.0% vs. 61.3%, p = 0.0203; respectively). There were no significant differences in the frequencies of complications, such as macrophage activation syndrome and disseminated intravenous coagulation, between the patients with elderly-onset or younger-onset AOSD. Serum ferritin levels were higher in the elderly-onset group than in the younger-onset group, albeit without statistical significance (median, 9,423 vs. 4,164 ng/mL, p = 0.1727). Pouchot score was lower in the elderly-onset group than in the younger-onset group (median score, 5.5 vs. 4.0, p = 0.0008); however, there was no significant difference in the mPouchot score between the two groups. Our analyses revealed that elderly-onset AOSD was associated with certain characteristics that were distinct from those of younger-onset AOSD and that the disease severity in patients with elderly-onset AOSD, determined by Pouchot score at the time of AOSD diagnosis, was similar to or less than that in patients with younger-onset AOSD.
34351609 Infliximab Treatment Does Not Lead to Full TNF-α Inhibition: A Target-Mediated Drug Dispo 2022 Jan BACKGROUND AND OBJECTIVE: Infliximab, an anti-tumour necrosis factor (TNF)-α monoclonal antibody, has been approved in chronic inflammatory disease, including rheumatoid arthritis, Crohn's disease and ankylosing spondylitis. This study aimed to investigate and characterise target-mediated drug disposition of infliximab and antigen mass turnover during infliximab treatment. METHODS: In this retrospective cohort of 186 patients treated with infliximab for rheumatoid arthritis, Crohn's disease or ankylosing spondylitis, trough infliximab concentrations were determined from samples collected between weeks 0 and 22 after treatment initiation. Target-mediated pharmacokinetics of infliximab was described using target-mediated drug disposition modelling. Target-mediated elimination parameters were determined for rheumatoid arthritis and Crohn's disease, assuming ankylosing spondylitis with no target-mediated elimination. RESULTS: The quasi-equilibrium approximation of a target-mediated drug disposition model allowed a satisfactory description of infliximab concentration-time data. Estimated baseline TNF-α amounts were similar in Crohn's disease and rheumatoid arthritis (R0 = 0.39 vs 0.46 nM, respectively), but infliximab-TNF complex elimination was slower in Crohn's disease than in rheumatoid arthritis (k(int) = 0.024 vs 0.061 day(-1), respectively). Terminal elimination half-lives were 13.5, 21.5 and 16.5 days for rheumatoid arthritis, Crohn's disease and ankylosing spondylitis, respectively. Estimated amounts of free target were close to baseline values before the next infusion suggesting that TNF-α inhibition may not be sustained over the entire dose interval. CONCLUSIONS: The present study is the first to quantify the influence of target antigen dynamics on infliximab pharmacokinetics. Target-mediated elimination of infliximab may be complex, involving a multi-scale turnover of TNF-α, especially in patients with Crohn's disease. Additional clinical studies are warranted to further evaluate and fine-tune dosing approaches to ensure sustained TNF-α inhibition.
33628335 The value of anti-CarP and anti-PAD4 as markers of rheumatoid arthritis in ACPA/RF negativ 2021 BACKGROUND: Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs). METHODS: A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies. RESULTS: Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs (r (s) = 0.39), RF and ACPAs, (r (s) = 0.3) and RF and anti-CarP, (r (s) = 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF. CONCLUSION: Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.
34300360 Comparison of Psoriatic Arthritis and Rheumatoid Arthritis Patients across Body Mass Index 2021 Jul 20 Abnormal body mass index (BMI) was associated with worse rheumatic markers in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Aiming to describe PsA and RA patients stratified by BMI, we performed a descriptive study in PsA and RA patients (two distinct cohorts) in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry. New users of biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) were stratified by BMI at the start of their treatment (underweight, normal weight, overweight, obese). The PsA underweight and normal weight categories were merged. Age at disease onset and further characteristics at the start of the first b/tsDMARD treatment were compared across BMI categories vs. the corresponding normal weight group. The study included 819 PsA (36.5% overweight, 23.8% obese) and 3217 RA patients (4.4% underweight, 31.8% overweight, 17.0% obese). Compared to the corresponding normal weight group, PsA and RA obese patients had significantly (p < 0.05) higher C-reactive protein, worse disease activity, and lower quality of life (QoL). Obese PsA patients had significantly worse skin manifestation and pain, while obese RA patients had significantly higher erythrocyte sedimentation rate and tender joint counts, as well as lower seropositive prevalence. To conclude, obese PsA and RA patients presented worse disease activity and poorer QoL than those with normal weight.
35126146 Tumor Necrosis Factor Alpha -308G/A Gene Polymorphisms Combined with Neutrophil-to-Lymphoc 2021 Background: TNF-α has been reported to be closely associated with autoimmune inflammatory diseases. This study aims to investigate the role of TNF-α -308(rs1800629) G/A gene polymorphisms as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of TNF inhibitors (TNFi) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriasis arthritis (PsA). Methods: A total of 515 subjects (181 AS, 144 RA, 48 PsA, 10 hyperbilirubinemia, 10 hyperlipidemia and 122 healthy control) were recruited in this study. The accuracy of RT-PCR methods for identifying individual TNF-α -308 genotypes was assessed using sequencing as the gold standard. Baseline NLR and PLR of patients with AS, RA and PsA and healthy controls (HC) were calculated and compared. Meanwhile, differences between responders and non-responders to TNFi treatment as well as between individuals with and without adverse effects (AE) among responders were compared. Results: The RT-PCR method is stable and reliable for TNF-α -308G/A gene polymorphism analysis, independent of sample status. The GG genotype was overwhelmingly represented, with relatively few GA genotype, whilst the AA genotype was not detected in this study. There was no observed association between TNF-α-308G/A polymorphism and susceptibility in AS, RA or PsA patients. Patients with AS, RA, and PsA had a higher NLR, compared to the HC group. Apart from PsA patients, AS and RA patients had a higher PLR, compared to the HC group. NLR was positively correlated with PLR. Furthermore, a lack of response was more frequently observed in AS and RA patients that carrying the GA genotype than the GG genotype. AS and RA patients with AE had higher NLR and PLR, compared with the non-AE group. Conclusion: Our study preliminarily shown that combining TNF-α -308G/A polymorphisms with NLR and PLR can predict the responsiveness and safety of anti-TNF therapy in patients with AS or RA.
32866681 Human dendritic cell-derived osteoclasts with high bone resorption capacity and T cell sti 2021 Jan Osteoclasts are typically differentiated from monocytes (Mo-OC). A subset of osteoclasts (DC-OC) that are differentiated from dendritic cells (DC) has been reported in the arthritic mice model. However, little information is available on DC-OC in humans. The present study applied both in vitro and in vivo experiments to determine the function and pathological significance of DC-OC. DC-OC were differentiated from human monocyte-derived DC and their bone resorption and antigen-presenting functions were investigated. Synovial tissue samples from patients with rheumatoid arthritis were examined for the presence and characteristics of DC-OC. DC-OC differentiated from DC in the presence of M-CSF and RANKL in vitro were demonstrated to be cathepsin K-positive and TRAP-positive multinucleated giant cells. The DC-OC showed stronger bone resorption ability than monocyte-derived osteoclast (Mo-OC) as observed with the pit formation assay. The DC-OC retained CD11c positivity and expressed costimulatory molecules, unlike Mo-OC. T-cells proliferated when co-cultured with DC-OC, but not with Mo-OC. The addition of abatacept to the cocultures reduced T-cell stimulating activity of DC-OC. Abatacept inhibited the differentiation of monocytes into Mo-OC but did not suppress the differentiation of DC into DC-OC. TRAP-positive and CD86-positive DC-OC were detected in the synovial membranes of rheumatoid arthritis patients but not in patients with osteoarthritis. Human DC-OC demonstrated T-cell stimulating activity in addition to osteolytic activity. We further observed this subset of osteoclasts in the inflammatory synovial membrane of patients with rheumatoid arthritis. Such deviations from normal bone metabolism contribute to the inflammation and bone destruction in chronic inflammatory diseases such as rheumatoid arthritis.
33658830 Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns 2021 INTRODUCTION: N6-methyladenosine (m6A) is the most frequent internal modification in eukaryotic mRNAs and is closely related to the occurrence and development of many diseases, especially tumors. However, the relationship between m6A methylation and rheumatoid arthritis (RA) is still a mystery. METHODS: Two high-throughput sequencing methods, namely, m6A modified RNA immunoprecipitation sequence (m6A-seq) and RNA sequence (RNA-seq) were performed to identify the differentially expressed m6A methylation in human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A after stimulation with TNF-α. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to obtain enriched GO terms and significant KEGG pathways. Then, four candidate genes, Wilms tumor 1-associating protein (WTAP), receptor-interacting serine/threonine protein kinase 2 (RIPK2), Janus kinase 3 (JAK3) and tumor necrosis factor receptor SF10A (TNFRSF10A) were selected to further validate the m6A methylation, mRNA and protein expression levels in MH7A cells and synovial tissues of adjuvant arthritis (AA) rats by RT-qPCR and Western blot. RESULTS: Using m6A-seq, we identified a total of 206 genes with differentially expressed m6A methylation, of which 118 were significantly upregulated and 88 genes were significantly downregulated. Likewise, 1207 differentially mRNA expressed mRNAs were obtained by RNA-seq, of which 793 were upregulated and 414 downregulated. Further joint analysis showed that the m6A methylation and mRNA expression levels of 88 genes changed significantly, of which 30 genes displayed increased m6A methylation and decreased mRNA expression, 57 genes displayed decreased m6A methylation and increased mRNA expression increased, and 1 gene displayed increased m6A methylation and increased mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in inflammation-related pathways, cell proliferation and apoptosis. In addition, the validations of WTAP, RIPK2, JAK3 and TNFRSF10A were in accordance with the m6A and RNA sequencing results. CONCLUSION: This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and RA related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent.
34285602 The Importance of Outcome Measures in the Management of Inflammatory Rheumatic Diseases. 2021 Rheumatic inflammatory diseases include a diverse and heterogeneous group of multifaceted disorders in which clinical history and physical examination are essential to make treatment choices and for optimizing outcomes. Composite outcome measures have become very relevant in rheumatology to evaluate disease activity as they capture the most important dimensions of the disease into one single measure. Most outcome measures may include disease manifestations, laboratory data, physician examination as well as the patient perspective as different outcome dimensions of the disease into a simple index. These outcome measures have proved their utility for guiding treatment in treat-to- target strategies and personalized medicine, with remission being the ultimate goal. In this narrative review, we go over the most commonly used outcome measures in rheumatoid arthritis, spondyloarthropathies, including psoriatic arthritis, and systemic lupus erythematosus to provide a practical summary for clinicians for everyday routine care.
34026055 Allicin regulates Treg/Th17 balance in mice with collagen-induced arthritis by increasing 2021 May To study the role of Allicin in regulating Treg/Th17 ratio in splenic lymphocyte by increasing the expression of MEKK2 protein in MAPK signaling pathway, and to explore the mechanism of immune response in mice with collagen-induced arthritis (CIA). Mouse CIA model was induced by chicken collagen type II, and experimental mice were randomly divided into NC group, Model group, and Allicin group. HE staining was used to compare the degree of joint pathological damage in mice of each group, and Masson staining to observe the proliferation of collagen tissue in each group. Flow cytometry detected Treg/Th17 ratio in splenic lymphocytes. Furthermore, RT-PCR and WB were used to detect the mRNA and protein expression of related transcription factors and inflammatory factors Foxp3, ROR-γt, and IL-17A, as well as MEK2 protein expression in splenic lymphocytes. The results showed that Allicin treatment could reduce the severity of arthritis and the proliferation of collagen fibers on the surface of cartilage and bone joints in CIA mice. Compared with NC group, Treg decreased and Th17 increased in spleen lymphocyte of Model group (p < .01); after Allicin treatment, Treg increased while Th17 decreased significantly (p < .01). Meanwhile, MEKK2 protein expression in spleen lymphocyte of Model group decreased compared to that in NC group (p < .01), and MEK2 protein expression increased significantly after Allicin treatment (p < .01). To sum up, the present study suggests that MEKK2 protein plays an important role in the pathogenesis of CIA model. In terms of mechanism, Allicin may play a therapeutic role in rheumatoid arthritis (RA) by increasing the expression of MEKK2 protein and affecting Treg/Th17 ratio.
33221885 Proinflammatory and bone protective role of calcitonin gene-related peptide alpha in colla 2021 Apr 6 OBJECTIVES: Calcitonin gene-related peptide alpha (αCGRP) represents an immunomodulatory neuropeptide implicated in pain perception. αCGRP also functions as a critical regulator of bone formation and is overexpressed in patients with rheumatoid arthritis (RA). In the present study, we investigated the role of αCGRP in experimental RA regarding joint inflammation and bone remodelling. METHODS: Collagen II-antibody-induced arthritis (CAIA) was induced in wild type (WT) and αCGRP-deficient (αCGRP-/-) mice. Animals were monitored over 10 and 48 days with daily assessments of the semiquantitative arthritis score and grip strength test. Joint inflammation, cartilage degradation and bone erosions were assessed by histology, gene expression analysis and µCT. RESULTS: CAIA was accompanied by an overexpression of αCGRP in WT joints. αCGRP-/- mice displayed reduced arthritic inflammation and cartilage degradation. Congruently, the expression of TNF-α, IL-1β, CD80 and MMP13 was induced in WT, but not αCGRP-/- animals. WT mice displayed an increased bone turnover during the acute inflammatory phase, which was not the case in αCGRP-/- mice. Interestingly, WT mice displayed a full recovery from the inflammatory bone disease, whereas αCGRP-/- mice exhibited substantial bone loss over time. CONCLUSION: This study demonstrates a proinflammatory and bone protective role of αCGRP in CAIA. Our data indicate that αCGRP not only enhances joint inflammation, but also controls bone remodelling as part of arthritis resolution. As novel αCGRP inhibitors are currently introduced clinically for the treatment of migraine, their potential impact on RA progression warrants further clinical investigation.
34873553 Are There Any Ethnic Differences in the Response to Baricitinib for the Treatment of Rheum 2021 Nov Introduction Baricitinib is an oral synthetic Janus Kinase inhibitor that inhibits JAK1 and JAK2, and the new kid on the block in the treatment of rheumatoid arthritis (RA). To date, there are no studies comparing the clinical benefit of baricitinib in RA between different ethnicities. Ethnicity plays a role in the effectiveness of therapeutic agents. Given the large multi-ethnic population of Leicestershire in the United Kingdom and the range of new therapeutics in RA, we reviewed our cohort of patients with RA to see whether there is any difference in baricitinib Disease Activity Score 28 (DAS28) response between the Asian and White cohorts. Methods This was a retrospective study. The patients included were those under the care of rheumatology at University Hospitals of Leicester (UHL) with a diagnosis of RA and either receiving baricitinib or had received it in the past. Data was collected using the UHL information technology systems, clinic letters and pharmacy records. In addition to ethnicity, we reviewed patient age, gender, concurrent disease-modifying anti-rheumatic drugs (DMARDs) used, previous biologics used, baseline and post-treatment DAS28, dropout from therapy, baseline biochemical assays (anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) status) and radiographic findings. An independent t-test was used to compare continuous data, and Pearson's chi-squared test was used to compare categorical data. Results A total of 120 patients were included in the analysis, and data were analysed with Portable Format for Analytics (PFA). There was no statistically significant difference in the mean DAS28 at baseline (Asian: 5.17 versus White: 4.65; p-value = 0.107) and post-treatment (Asian: 2.8 versus White: 3.3; p-value = 0.404). Comparing both ethnicities, there was no statistically significant difference in previous biologics used, anti-CCP and RF titres, and radiographic findings of erosions. Conclusion This is the first study of its kind, and it found no significant difference in baricitinib response between the Asian and White cohorts. Our study had certain limitations, and future studies will be needed to evaluate this subject further. Such data is important as it can contribute to a body of evidence that may in the future help inform clinical decision-making.
34447101 Oral Health and Rheumatoid Arthritis: A Case Control Study. 2021 Jun INTRODUCTION: Association between oral health and rheumatoid arthritis is well established. Oral health-related quality of life was determined in patients diagnosed with rheumatoid arthritis (RA). MATERIALS AND METHODS: This study was conducted among 45 patients (males 25 and female 20) (Group I) of RA and 45 healthy participants as control (Group II). Disease activity score 28 test, health assessment questionnaire (HAQ), and general oral health assessment index (GOHAI) questionnaire were applied. RESULTS: The mean HAQ score in Group I was 1.14 and in Group II was 0.36. The mean GOHAI score in Group I was 36.4 and in Group II was 52.8. The mean HAQ in males was 0.94 and in females was 34.6. The mean GOHAI in males was 12.6 and in females was 38.2. In Group I, there were 15 patients with HAQ level 1 and 30 with HAQ level 2 and in Group II was 40 with HAQ levels 1 and 5 with HAQ level 2. In Group I, 42 had Dt GOHAI = 0 and 3 had Dt GOHAI = 1 and in Group II, 10 had Dt GOHAI = 0 and 35 had Dt GOHAI = 1. The difference was statistically significant (P < 0.05). There was a statistically significant difference in the mean value of HAQ and GOHAI in degree of disease activity (P < 0.05). There was an increase in HAQ and decreases GOHAI scores with the deterioration of disease. There was a correlation between age and involved joints with HAQ and inverse relationship between age and involved joints with GOHAI. CONCLUSION: Authors found that RA patients had poor oral health quality of life. It was found that aging and with the deterioration of disease, GOHAI, and the oral health quality of life of patients decreased.
35096912 Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis. 2021 Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.
33842513 Palindromic Rheumatism: Just a Pre-rheumatoid Stage or Something Else? 2021 Palindromic rheumatism (PR), a unique clinical entity, has a characteristic clinical presentation with a relapsing/remitting course. It is established that most patients with PR evolve to chronic disease, of which rheumatoid arthritis (RA) is by far the most common. The relationship between PR and RA is unclear, with similarities and differences between the two, and not all patients evolve to RA in the long-term. Therefore, PR is clearly a pre-RA stage for most, but not all, patients. Autoimmunity plays a substantial role in PR, with the same characteristic autoantibody profile observed in RA, although with some differences in the immune response repertoire. Autoinflammation may also be relevant in some cases of PR. Prognostic factors for RA progression are identified but their exact predictive value is not clear. There are several unmet needs in PR, such as the diagnostic criteria and clinical case definition, the pathogenic mechanisms involved in the unusual clinical course, and the evolution to RA, and our understanding of the therapeutic strategy that could best avoid progression to persistent and potentially destructive arthritis.
33673675 Comprehensive Management of Rheumatic Diseases Affecting the Temporomandibular Joint. 2021 Feb 27 The temporomandibular joint (TMJ) is a synovial joint and thus is vulnerable to the afflictions that may affect other joints in the fields of rheumatology and orthopedics. Too often temporomandibular complaints are seen strictly as dental or orofacial concerns. Similarly, patients with known rheumatic disease may not have their TMJs included in routine screening and monitoring protocols. The purpose of this review is to highlight the rheumatic conditions likely to affect the TMJ and outline medical and surgical management in these patients with a focus on the need for continued patient reassessment and monitoring.
33407952 Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory res 2021 Jan 6 BACKGROUND: Circ_0000396 was found to be down-regulated in the rheumatoid arthritis (RA) patients and had a high diagnostic value. However, the function and mechanisms underlying circ_0000396 in RA progression remain unclear. METHODS: The expression of circ_0000396, microRNA (miR)-203 and HMG-box transcription factor 1 (HBP1) was detected using qRT-PCR and western blot. The proliferative and apoptotic capabilities of rheumatoid arthritis synovial fibroblasts (RASFs) were measured by colony formation, CCK-8, flow cytometry and western blot assays, respectively. The levels of interleukins (IL)-6, IL-1β, IL-8 and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA). The target correlations between miR-203 and circ_0000396 or HBP1 were validated using pull-down and dual-luciferase reporter assay. RESULTS: Circ_0000396 was decreased in RA synovial tissues and RASFs, and overexpression of circ_0000396 suppressed cell proliferation, induced cell apoptosis and reduced the release of inflammatory cytokine IL-6, IL-1β, IL-8 and TNF-α in RASFs, while circ_0000396 deletion functioned oppositely. MiR-203 was confirmed to be a target of circ_0000396, and miR-203 reversed the protective effects of circ_0000396 on the dysfunction and inflammation of RASFs. HBP1 was a target of miR-203, and silencing miR-203 inhibited RASFs malignant changes by regulating HBP1. In addition, circ_0000396 could regulate HBP1 by sponging miR-203, and HBP1 decrease attenuated the effects of circ_0000396 on RASF growth and inflammation. CONCLUSION: Circ_0000396 inhibited the growth and inflammation in RASFs by regulating miR-203/HBP1 axis, providing a potential therapeutic target for RA.
34747452 Assessing Predictors of Rheumatoid Arthritis Associated Interstitial Lung Disease using Qu 2021 Nov 8 OBJECTIVE: To assess predictors of subclinical rheumatoid arthritis-associated interstitial lung disease (RA-ILD) using quantitative lung densitometry (qLD). METHODS: RA patients underwent multi-detector row computed tomography scanning at baseline and after an average of 39 months. Scans were analyzed with qLD for the percentage of lung parenchyma with high attenuation areas (%HAA: the percentage of voxels of -600 to -250 Hounsfield units). Additionally, a pulmonary radiologist calculated an Expert Read Score (ERS) for RA-ILD features. Generalized linear models were used to identify indicators of baseline %HAA and predictors of %HAA change. RESULTS: Baseline %HAA was assessed in 193 RA patients and 106 had repeat qLD assessment. %HAA was correlated with ERS (Spearman's rho = 0.261; p< 0.001). Significant indicators of high baseline %HAA (>10% of lung parenchyma with high attenuation) included female sex, higher pack-years of smoking, higher body mass index, and anti-CCP ≥ 200 units, collectively contributing an area under the receiver operator curve (AUROC)=0.88 (95% CI 0.81-0.95). Predictors of %HAA increase, occurring in 49% with repeat qLD, included higher baseline %HAA, presence of MUC5B minor allele, and absence of HLA-DRB1 shared epitope (AUC-ROC = 0.69; 95% CI 0.58-0.79). The association of the MUC5B minor allele with %HAA change was higher among men and those with higher cumulative smoking. Within the group with increased %HAA, anti-CCP level was significantly associated with a greater increase in %HAA. CONCLUSIONS: %HAA, assessed with qLD, was linked to several known risk factors for RA-ILD and may represent a more quantitative method to identify RA-ILD and track progression than expert radiologist interpretation.
34322942 Association between allergic or autoimmune diseases and incidence of endometriosis: A nest 2021 Nov PROBLEM: Immune responses were reported to be associated with the pathogenesis of endometriosis. However, previous studies of an association between allergic or autoimmune diseases and endometriosis have reported inconsistent results. We investigated the association between allergic or autoimmune diseases and the incidence of endometriosis. METHOD OF STUDY: Using a large-scale health insurance claims database in Japan, we identified patients with endometriosis diagnosed between April 2011 and August 2018. For each case, we identified up to four controls with the same age and registration month. Conditional logistic regression analyses were conducted to evaluate the incidence rate ratio (IRR) of endometriosis in women with allergic diseases (asthma, allergic rhinitis, urticaria, atopic dermatitis, allergic conjunctivitis, and type 1 allergies combined), systemic lupus erythematosus, and rheumatoid arthritis compared with women without these diseases. RESULTS: We identified 30 516 cases with endometriosis and 120 976 control participants. Mean age at registration was 30 years. There were significant positive associations between type 1 allergy and endometriosis (IRR, 1.10; 95% confidence interval, 1.06-1.13) and between rheumatoid arthritis and endometriosis (IRR, 1.31; 95% confidence interval, 1.05-1.64). Diagnosis of systemic lupus erythematosus was not associated with increased incidence of endometriosis. Among the different allergic diseases, allergic rhinitis, urticaria, and allergic conjunctivitis were associated with the increased incidence. CONCLUSION: Several allergic diseases were associated with an increased incidence of endometriosis. A higher incidence was also observed in patients with rheumatoid arthritis. Further studies are warranted to elucidate the influence of immune responses on the development of endometriosis.
33915820 Humoral Immunity to Varicella Zoster Virus in Patients with Systemic Lupus Erythematosus a 2021 Apr 1 BACKGROUND: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). METHODS: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. RESULTS: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. CONCLUSIONS: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases.
32533534 Intestinal microbiota and juvenile idiopathic arthritis: current understanding and future 2021 Feb BACKGROUND: Juvenile idiopathic arthritis (JIA) characterized by arthritis of unknown origin is the most common childhood chronic rheumatic disease, caused by both host genetic factors and environmental triggers. Recent evidence has mounted to focus on the intestinal microbiota, a potentially recognized set of environmental triggers affecting JIA development. Here we offer an overview of recently published animal and human studies that support the impact of intestinal microbiota in JIA. DATA SOURCES: We searched PubMed for animal and human studies publications with the search terms "intestinal microbiota or gut microbiota" and "juvenile idiopathic arthritis or juvenile chronic arthritis or juvenile rheumatoid arthritis or childhood rheumatoid arthritis or pediatric rheumatoid arthritis". RESULTS: Several comparative studies have demonstrated that intestinal microbial alterations might be triggers in disease pathogenesis. Alternatively, a slice of studies has suggested environmental triggers in early life might disrupt intestinal microbial colonization, including cesarean section, formula feeding, and antibiotic exposure. Aberrant intestinal microbiota may influence the development of JIA by mediating host immune programming and by altering mucosal permeability. CONCLUSIONS: Specific microbial factors may contribute to the pathogenesis of JIA. Intensive studies, however, are warranted to investigate the causality between intestinal dysbiosis and JIA and the mechanisms behind these epidemiologic relationships. Studies are also needed to design the best interventional administrations to restore balanced intestinal microbial communities.