Features Of Rheumatoid Arthritis Research Articles

Rheumatoid arthritis characteristics and classification of heat and cold patterns–an observational study

IntroductionTraditional Chinese medicine (TCM) has been proven to be an effective complementary therapy in treating rheumatoid arthritis (RA). The cold pattern and the heat pattern were the two main TCM patterns for RA, which is crucial for TCM treatment. The cold pattern is characterized by fear of cold and wind, joint pain with a thin white tongue coating which can be relieved by hot herbs. In contrast, heat pattern patients suffer from severe joint pain with a yellow coating, with red swelling of the skin and high skin temperature which can be relieved by cooling herbs. ObjectiveWe aimed to classify the heat and cold patterns in RA patients with cluster analysis and factor analysis. Moreover, we aimed to explore the association of RA characteristics between these two patterns. Methodsand Design: A cross-sectional observational research method was used, and data was collected on 300 RA patients in Hangzhou in China. Signs and symptoms associated with RA were clustered using SPSS 22.0 software. In addition, factor analysis was also used for the classification. After classification of heat and cold patterns, characteristics and treatment of the RA participants between the two patterns were explored. ResultsRA patients in the study were divided into two categories using cluster analysis. Twenty-two symptoms in the first category were included in the heat pattern of RA patients. After factor analysis, nine principal components were extracted to heat pattern. The component with the highest eigenvalue (2.530) were mainly contributed by shortness of breath, palpitation, heavy limbs, chest tightness and yellow greasy tongue with high factor loading values (0.765, 0.703, 0.504, 0.429 and 0.402, respectively). Ten symptoms in the second category were included in the cold pattern of RA patients. Four principal components were extracted to cold pattern. The component with the highest eigenvalue (2.089) were mainly contributed by joint distension and pain, joint stiffness, fatigue and upset with high factor loading values (0.597, 0.590, 0.491 and 0.481, respectively). Although there were no statistical differences between the levels of rheumatoid factor and anti-cyclic peptide containing citrulline (anti-CCP), the levels of C-reactive protein, platelet count and the disease activity score using 28 joint counts were significantly higher in the heat pattern RA patients compared to the ones in cold pattern. Moreover, heat pattern RA patients were more likely to be prescribed two more disease-modifying anti-rheumatic drugs (DMARDS) combined with Methotrexate (MTX) (70.59% versus 49.72%; P = 0.000). ConclusionsIn conclusion, heat and cold patterns in RA patients could be classified well using cluster analysis and factor analysis. Most of RA patients with heat pattern were active and likely to be prescribed two more DMARDs combined with MTX.

Sarsasapogenin, a principal active component absorbed into blood of total saponins of Anemarrhena, attenuates proliferation and invasion in rheumatoid arthritis fibroblast-like synoviocytes through downregulating PKM2 inhibited pathological glycolysis.

Increased glycolytic in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) not only contributes to early-stage disease pathogenesis but leads to sustained proliferation of FLS. Given the importance of PKM2 in glycolysis and apoptosis, PKM2 is considered a potential therapeutic and drug discovery target in RA. Total saponins of anemarrhena (TSA), a class of steroid saponins, originated from Anemarrhena asphodeloides Bge. In this study, we verified that 200 mg/kg TSA could significantly alleviate inflammation and the pathological characteristics of RA and inhibit synovial hyperplasia in AA rats. We confirmed that sarsasapogenin (SA) was the principal active ingredient absorbed into the blood of TSA by the UPLC/Q Exactive MS test. Then we used TNF-α-induced MH7A to get the conclusion that 20 μM SA could effectively inhibit the glycolysis by inhibiting the activity of PKM2 tetramer and glucose uptake. Moreover, 20 μM SA could suppress proliferation, migration, invasion, and cytokine release of FLS, interfere with the growth cycle of FLS, and induce FLS apoptosis by depressing the phosphorylation of PKM2. At last, In-1, a potent inhibitor of the PKM2 was used to reverse verify the above results. Taken together, the key mechanisms of SA on RA treatment through downregulating the activity of PKM2 tetramer and phosphorylation of PKM2 inhibited pathological glycolysis and induced apoptosis to exert inhibition on the proliferation and invasion of RA FLS.

DNA methylation change of HIPK3 in Chinese rheumatoid arthritis and its effect on inflammation.

Homeodomain-interacting protein kinase 3 (HIPK3) plays an important role in cell proliferation, apoptosis, and inflammation. Over-expression of HIPK3 in immune cells in rheumatoid arthritis (RA) has been reported. In this study, we investigated blood methylation levels and clinical characteristics of RA in a Chinese population. A total of 235 patients with RA, 30 with osteoarthritis (OA), and 30 matched healthy controls were recruited. The methylation status of seven CpGs in the differentially methylated region of HIPK3 (cg05501357) was measured using targeted methylation-sequencing technology. The association between methylation haplotypes and the overall methylation status of HIPK3 with clinical characteristics was assessed using generalized linear regression. All seven CpGs showed hypomethylation status in RA blood compared with OA and normal individuals (overall p= 1.143×10-8 and FDR= 2.799×10-7), which is consistent with the previously reported high expression of HIPK3 in RA immune cells. Among all seven CpGs, 33286785 showed the highest predictive power with an area under the curve (AUC) of 0.829; we received a higher AUC=0.864 when we combined HIPK3 with anti-citrullinated protein antibodies (ACPA -) and rheumatoid factor (RF +) in the prediction model, indicating that when a patient's ACPA is negative, HIPK3 can assist RF as a new clinical index for the diagnosis of RA. We also found that HIPK3 methylation levels were negatively correlated with C-reactive protein (CRP; r= -0.16, p= 0.01). Methylation haplotypes were analyzed, and the full methylation haplotype (FMH; r= 0.16, p= 0.01) and full non-methylation haplotype (FNH; r= 0.18, p= 0.0061) were negatively correlated with CRP. Circulating blood methylation levels in the protein region of HIPK3 can be utilized as a supportive diagnostic biomarker and CRP level indicator for RA.

Hypoxia and TNF-α Synergistically Induce Expression of IL-6 and IL-8 in Human Fibroblast-like Synoviocytes via Enhancing TAK1/NF-κB/HIF-1α Signaling.

Hypoxia and increased levels of inflammatory cytokines in the joints are characteristics of rheumatoid arthritis (RA). However, the effects of hypoxia and tumor necrosis factor-α (TNF-α) on interleukin (IL)-6 and IL-8 production on fibroblast-like synoviocytes (FLSs) remain to be clarified. This study aimed to explore how hypoxia and TNF-α affect the expression of IL-6 and IL-8 in human FLSs isolated from RA patients. Hypoxia or TNF-α treatment alone significantly increased the expression and promoter activity of IL-6, IL-8, and hypoxia-inducible factor-1α (HIF-1α). Treatment of hypoxic FLSs with TNF-α further significantly elevated the expression of these cytokines and enhanced promoter activity of HIF-1α, which was abrogated by treatment with the HIF-1α inhibitor YC-1. Similarly, TNF-α alone elevated the phosphorylation and promoter activity of nuclear factor-κBp65 (NF-κBp65) in the FLSs. These effects were further enhanced by the combined treatment of hypoxia and TNFα but were attenuated by the NF-κB inhibitor BAY11-7082. NF-κB-p65 inhibition decreased the effect of TNF-α on HIF-1α upregulation in the FLSs in response to hypoxia. The combination of hypoxia and TNF-α also significantly upregulated transforming growth factor-β-activated kinase 1 (TAK1) expression, and silencing TAK1 dramatically decreased NF-κB-p65, HIF-1α, IL-6, and IL-8 expression under the same conditions. Our results indicate that hypoxia and TNF-α synergistically increase IL-6 and IL-8 expression in human FLSs via enhancing TAK1/NF-κB/HIF-1α signaling.

Identification and Development of Synovial B-Cell-Related Genes Diagnostic Signature for Rheumatoid Arthritis.

The aim of the study was to investigate the landscape of B-cell-related gene expression profiling in rheumatoid arthritis (RA) synovium and explore the biological and clinical significance of these genes in RA. Expression profiling of synovial biopsies from subjects with 152 RA patients, 22 osteoarthritis (OA) patients, and 28 healthy controls was downloaded from the Gene Expression Omnibus database. Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate the abundance of infiltrated immune cells, and the results were validated using immunohistochemical staining. GSEA was employed to decipher differences in B-cell-related biological pathways. B-cell-related differential expression genes (BRDEGs) were screened, and BRDEGs-based model was developed by machine learning algorithms and evaluated by an external validation set and clinical RA cohort, then biological functions were further analyzed. High levels of immune cell infiltration and B-cell-related pathway activation were revealed in RA synovium. BRDEGs were screened, and three key molecular markers consisting of FAS, GPR183, and TFRC were identified. The diagnosis model was established, and these gene markers have good discriminative ability for RA. Molecular pathological evaluation confirmed RA patients with high-risk scores presented higher levels of B-cell activation and RA characteristics. In addition, a competitive endogenous RNA network was established to elucidate the molecular mechanisms of the posttranscriptional network. We described the B-cell-related molecular landscape of RA synovium and constructed a molecular diagnostic model in RA. The three genes FAS, GPR183, and TFRC may be potential targets for clinical diagnosis and immunoregulatory therapy of RA.

Challenges of Rheumatoid Arthritis Management in Sub-Saharan Africa in the 21st Century

In recent decades, several advances have been made in the management of rheumatoid arthritis (RA) both in the diagnostic field and in the therapeutic field. Unfortunately, RA remains poorly studied in black Africa. Epidemiological data are rare and controversial. The estimated prevalence of RA in Africa is about 0% - 2.54%. Risk factors associated with RA must be studied by taking into account special features of black Africa such as the low tobacco consumption in certain regions, the tropical climate and the high frequency of endemic parasitic and viral infections. The initially supposed mildness of RA in black Africa is increasingly challenged. The diagnosis is often made too late because of the scarcity of rheumatologists and ignorance. Diagnostic tools are limited to the clinical data, the erythrocyte sedimentation rate and radiographs as the other tools are poorly available. In addition, there are misconceptions in African communities, responsible for loss of sight during follow-up and treatment discontinuations. This is exacerbated by the shortage of disease-modifying anti-rheumatic drugs (DMARDs) and the inability to afford them. Furthermore, biological agents are very difficult to access. Further studies are essential to better understand the characteristics of RA in black Africa. Thus, collaborations between African and Western research teams seem very important. In order to make available the DMARDs especially biological agents, pharmaceutical companies can contribute through research partnerships. Moreover, governments should provide a better place for chronic inflammatory diseases in the programs against non-communicable diseases. Finally, training must also be promoted to increase the number of specialists and the level of knowledge of other health workers.

Importance of STAT3 Polymorphisms on the Risk and Clinical Characteristics of Rheumatoid Arthritis.

Signal transducer and activator of transcription 3 (STAT3) has been introduced as one of the critical genetic factors in the pathogenesis of rheumatoid arthritis (RA). Single nucleotide polymorphisms (SNPs) in microRNA binding sites, known as miRSNPs, are a class of common variants in the 3' untranslated regions of genes targeted by miRNAs. miRSNPs unbalance gene expression by disrupting the binding regions of microRNAs. In this study, we intended to evaluate the association of two miRSNPs with the risk of RA development and its clinical features. We studied 120 Iranian patients with RA and 125 non-RA subjects as controls. The genotypes and alleles of rs1053005 and rs1053023 in each individual were assessed by the high-resolution melting method. The distribution of STAT3 variants did not differ markedly in RA patients compared to healthy controls. Stratification analysis revealed that rs1053005 was linked with a higher concentration of C-reactive protein and an increased erythrocyte sedimentation rate, two indicators of inflammation and disease activity in RA patients. The rs1053023 variant was correlated with higher levels of creatinine as an indicator of renal involvement. Our data demonstrate an association between STAT3 variants and clinical characteristics of RA, such as disease activity and probably kidney impairment. However, we did not observe a significant relationship between the two targeted variants and a predisposition to RA.

Disease Activity Is More Associated with IL-1 Than with IL-6 in Patients with Rheumatoid Arthritis.

Interleukin-1 receptor antagonist (IL-1ra) concentration reflects and is proportional to IL-1 production. Both IL-1 and IL-6 are involved in the pathogenesis of rheumatoid arthritis (RA). However, the relationship of serum levels of these two cytokines to each other in RA patients is not well-understood. In this study, our objective was to analyze the possible linear correlation between IL-1ra and IL-6 in patients with RA, and how both are related to the inflammatory activity of the disease. IL-6 and IL-1ra levels were measured in 407 patients with RA. Linear regression and partial correlations were conducted to analyze the relationship between both cytokines, and their association with RA characteristics. No correlation was found between serum levels of IL-6 and IL-1ra (Pearson's r 0.031, p = 0.61). However, disease activity and acute phase reactants were positively and significantly associated with both cytokines. Nevertheless, after controlling for covariates, disease activity scores were more strongly associated with IL-1ra compared to IL-6. Circulating IL-6 and IL-1ra do not correlate with each other in RA patients. Although both are associated with disease activity and acute phase reactants, the relationship of disease activity to IL-1ra is greater than that to IL-6.

EXTRAARTICULAR MANIFESTATIONS OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a systemic autoimmune disease. The main characteristic of RA is persistent joint inammation resulting in joint damage and loss of function. Rheumatoid arthritis may lead to a variety of extra articular manifestations. Extra-articular organ involvement in RA is more frequently seen in patients with severe, active disease and is associated with increased mortality. The occurrence of these systemic manifestations is a major predictor of mortality in patients with RA. [1] Our case series attempts to provide a glimpse into the various extra articular manifestations of Rheumatoid arthritis. In total, 3 patients have been included for this case series. All 3 patients were a known case of Rheumatoid arthritis who presented with extra articular manifestations at MGM hospital, Kamothe.

Risk factors for rheumatoid arthritis-associated interstitial lung disease: a retrospective study.

The objective of this study was to assess clinical and imaging features of rheumatoid arthritis (RA) associated with interstitial lung disease (ILD), (RA-ILD) group, in comparison to RA without ILD (RA-C) and to identify the associated factors to ILD. This was a retrospective comparative study (from June 2015 to March 2022) including RA patients aged ≥18 years. The RA-C control group was matched according to age (±2 years), gender, and RA duration (±2 years). General data, RA characteristics, ILD features, and treatment modalities were recorded. Statistical analysis was performed to determine the predictive factors of ILD. A total of 104 patients were included (52 RA-ILD and 52 RA-C); sex ratio was 0.36. Mean age was 66.3±11 years (RA-ILD) versus 65.6±10.8 years (RA-C) (p=0.72). In comparison to RA-C, RA-ILD patients were significantly higher smokers (p=0.01) and physically inactive (p=0.01). Regarding RA features, RA-ILD patients have significantly increased positive anti-citrullinated peptide antibody (ACPA) (p=0.01), ACPA rate (p<0.001), erosive disease (p<0.001), and disease activity score (p<0.001). Mean time to ILD diagnosis was 5.85±7.16 years. Chest high-resolution computed tomography (HRCT) patterns of disease were identified: nonspecific interstitial pneumonia (NSIP) (28.8%), usual interstitial pneumonia (UIP) (17.3%), organizing pneumonia (OP) (25%), acute interstitial pneumonia (13.5%), and respiratory bronchiolitis (3.8%). Multivariate analysis identified smoking, high baseline DAS28 (disease activity score 28) and ACPA positivity as predictive factors of ILD. Our results confirmed the reported associated factors of ILD in RA (smoking, higher disease activity, ACPA positivity). Thus, we need to target the modifiable factors by supporting and educating RA patients to quit smoking and intensify disease modifying anti-rheumatoid drugs (DMARD) to reach remission.

Presence of Activating STAT3 Mutations in the CD8+ T Cells of Rheumatoid Arthritis Patients

Rheumatoid Arthritis (RA) is a systemic autoimmune disorder afflicting around 1% of the global population. It is treated with a variety of immunosuppressants typically progressing from first line therapies such as low dose methotrexate (MTX) or other disease modifying anti-rheumatic drugs (DMARDs) to second line treatments such as tumor necrosis factor (TNF) inhibitors or other biologics designed to target pro-inflammatory cytokines. Several factors are used to anticipate and measure disease severity including Disease Activity Measures (DAM) and positivity of rheumatoid factor (RF), antibodies to cyclic citrullinated protein (CCP), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Presence of anti-CCP antibody is the most specific of these markers of RA, and its presence may be associated with more severe disease. Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy characterized by clonal proliferation of natural killer or CD8+ T cells, somatic activating mutations in the signaling transducer and activator of transcription 3 (STAT3) gene, and clinical features including neutropenia and anemia. Interestingly, LGL leukemia is strongly associated with RA, with as high as 36% of patients exhibiting concomitant RA. There is significant overlap between the diseases. Both RA alone and in combination with LGL leukemia exhibit cytotoxic T cell expansions, HLA-DR4 enrichment, female bias, and RA-associated autoantibodies. The dominant molecular hallmark of LGL leukemia is somatic activating STAT3 mutation. Most patients exhibit increased activation of STAT3 through phosphorylation, and 50% or more patients have a mutation in STAT3, the most common being missense mutations, Y640F and D661Y. Of note, LGL leukemia patients with one or more STAT3 mutations are more likely to suffer from concomitant RA. Based on these observations, we hypothesized that STAT3 mutations would be enriched in RA patients compared to the general population and that the presence of mutations may correlate with specific clinical characteristics of RA. In this study, blood samples and demographic data were simultaneously collected from 96 RA patients at the UVA Rheumatology Clinic. CD8+ cells were isolated from blood samples and DNA was extracted and analyzed via droplet digital PCR to detect Y640F, D661Y, and S614R_G618R STAT3 mutations. Figure A shows that roughly 3% (3/96) of the RA samples had a STAT3 mutation in greater than 5% of the DNA analyzed. Additionally, an even larger proportion of RA patients had either Y640F or D661Y mutations at a rate of between 1:100 and 1:1000 cells (10/96 Y640F, 14/96 D661Y). These samples were classified as mutated for the purposes of statistical analysis. Of the 9 healthy control samples analyzed, only one exhibited a mutation of this size (1/9 Y640F, 0/9 D661Y). Correlation with clinical parameters showed similar disease manifestations between WT and STAT3 mutant samples. However, CCP differed between mutational types, with the Y640F group exhibiting higher positivity than the D661Y group (Figure B). Taken together, the increased presence of STAT3 activating mutations in CD8+ cells isolated from RA blood samples as well as the difference in CCP positivity between D661Y and Y640F mutational groups merits further investigation of these pathways in RA. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical characteristics of rheumatoid arthritis patients complicated with pulmonary nontuberculous mycobacterial disease: A cross-sectional case series study.

Pulmonary nontuberculous mycobacterial disease (pNTM) is a common pulmonary complication of rheumatoid arthritis (RA), but their association has rarely been researched. We aimed to reveal the clinical characteristics of RA with pNTM. Among all the RA patients who visited Tenri hospital from April 2017 to March 2018, we enrolled those fulfilling the 2007 ATS/IDSA diagnostic criteria of pNTM, and sex- and age- matched control group at a ratio of 1:5. Demographic characteristics were compared between the two groups. Among 865 RA patients, 35 (4.0%) patients were complicated with pNTM. RA patients with pNTM had significantly lower BMI and higher rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity. Bronchiectasis was the most frequent lesion, followed by clusters of small nodules, patchy consolidation and cavity. Multivariable logistic regression analysis revealed bronchiectasis as a strong independent associated factor of pNTM. Treatment for pNTM was needed in 14 of the 35 (40%) RA patients with pNTM and sputum negative conversion was accomplished in 11 of the 14 cases (78.6%). RA patients with lower BMI, RF/ACPA positivity, and bronchiectasis were associated with pNTM. Treatment for pNTM may attain sputum negative conversion and radiological improvement in patients with RA.

The Inhibitory Effect of CBD on Proinflammatory Cytokine, IL-6, in LPS-Mediated Inflamed THP-1 Differentiated Macrophage Cells

About 1.5 million Americans suffer from Rheumatoid Arthritis (RA), an autoimmune, chronic inflammatory disease with no cure. This is a condition in which the immune system mistakenly attacks healthy cells, leaving the body in a constant state of inflammation. A major characteristic of RA is unresolved inflammation specifically in the joints of the hands, wrists, and knees. People who have RA suffer from a lot of pain, experience bone, and joint deformity, and have a loss of function in the targeted areas. In patients with RA, the immune system is not working properly, and the immune responses are unregulated. Due to being an autoimmune disorder, our B cells are presenting healthy cells with autoantigens that trigger multiple signaling pathways that lead to the release of cytokines. A primary cytokine, IL-6, plays a role in the pathogenesis of RA due to its pro-inflammatory effects. IL-6 causes the release of acute phase proteins which cause fevers, iron deficiency, fatigue, fat and muscle loss, anorexia, and weakness. One way to treat RA is to target the inflammation directly by interrupting cytokine release. In this work, the effect of CBD was evaluated to determine if its application has the potential to decrease IL-6 expression/release by inflamed cells. Macrophages derived from THP-1 Cells cultured with PMA were treated with LPS to model inflammation in vitro and the expression of IL-6 was determined by ELISA to correlate in a dose-dependent manner to LPS.

Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. Microbial infection is considered a crucial inducer of RA. Alterations in the composition of intestinal bacteria in individuals with preclinical and established RA suggest a vital role of the gut microbiota in immune dysfunction characteristic of RA. However, the mechanisms by which gut dysbiosis contributes to RA are not fully understood. Furthermore, multiple therapies commonly used to treat RA may alter gut microbiota diversity, suggesting that modulating the gut microbiota may help prevent or treat RA. Hence, a better understanding of the changes in the gut microbiota that accompany RA should aid the development of novel therapeutic approaches. This mini-review discusses the impact of gut dysbiosis in the pathogenesis of RA, the selection of gut microbiota-related biomarkers for diagnosing RA, and provides examples of cross-modulation between the gut microbiota and some drugs commonly used to treat RA. Some suggestions and outlooks are also raised, which may help guide future research efforts.

Is the Calcium Score Useful for Rheumatoid Arthritis Patients at Low or Intermediate Cardiovascular Risk?

Cardiovascular disease, particularly myocardial infarction, is the leading cause of death of rheumatoid arthritis (RA) patients. The usefulness of the coronary artery calcification score (CACS), determined using cardiac computed-tomography (CT)-scan images, was assessed as a part of a cardiovascular work-up of RA patients at low or intermediate cardiovascular disease risk. This descriptive, cross-sectional, single-center study was conducted on patients with stable RA or that which is in remission. Each patient’s work-up included a collection of cardiovascular risk factors, laboratory analyses, an electrocardiogram, a supra-aortic trunks (SATs) echo-Doppler test and a cardiac CT scan. The primary endpoint was to determine the frequency of patients with a CACS > 100, indicating notable atherosclerosis. Fifty patients were analyzed: mean ± standard deviation age was 53.7 ± 7.5 years, 82% women. The CACS exceeded 100 in 12 (24%) patients (11 were at intermediate risk) and 2 of them underwent angioplasty for silent myocardial ischemia. Cardiovascular risk was reclassified from intermediate to high for 5 patients. Age according to sex and smoking status were significantly associated with that increase; no association was found with RA characteristics or treatments.

Syndecan-4 is correlated with disease activity and serological characteristic of rheumatoid arthritis

ObjectivesTo describe the feature of expression of syndecan-4 in serum, synovial fluid (SF) and synovium in rheumatoid arthritis (RA) patients, and to analyze the correlation of syndecan-4 with disease activity and serological characteristic of RA.MethodsSyndecan-4 in sera of 60 RA patients, 20 osteoarthritis (OA) patients, 20 healthy controls, and in SF of 25 RA patients and 25 OA patients were tested by enzyme linked immunosorbant assay. The expressions of syndecan-4 in synovium of RA and OA patients were detected by immunohistochemistry. The expression of syndecan-4 on synovial fibroblasts from RA and OA patients were detected by immunofluorescence. The correlation between serum syndecan-4 concentration and disease activity were analyzed in RA patients.ResultsThe serum syndedcan-4 concentration was significantly higher in RA patients than in OA patients and healthy controls, and was higher in rheumatoid factor (RF)-positive RA patients than in RF-negative ones. Syndecan-4 concentration in SF of RA patients was comparable with OA patients. Syndecan-4 expression in synovial tissue was similar between RA and OA patients. The syndecan-4 concentration was significantly lower in SF than in serum of RA and OA patients. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients.ConclusionThe serum syndecan-4 concentration was higher in RA patients than in OA patients, and significantly higher in RF-positive RA patients than in RF-negative ones. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients.

AB1161 COVID-19 IN MY RA CLINIC: DATA FROM QUESTIONNAIRE, VACCINATION, INFECTION AND FLARES FROM THE RA LOUVAIN BRUSSELS COHORT

BackgroundOver 5 million deaths from the COVID-19 disease have been reported in the world. Patients (pts) living with rheumatoid arthritis (RA) affecting the immune system or under immunosuppressive agent are considered as a high risk population for a SARS-CoV-2 infection. Since no antiviral treatment is available, the vaccination is a major option.ObjectivesThe aim of this study is to evaluate in our RA cohort a questionnaire about the COVID-19 vaccination willingness, to analyse the vaccination rate, the number of COVID infection, the RA flares and the side effects.MethodsWe included pts with RA from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 classification criteria. A simple and standard questionnaire about the vaccine willingness was distributed in 2020 before the vaccination. From January to December 21, the rate of vaccination was calculated. The number of Covid infections, RA flares, therapy switches and side effects were also collected. All patient and RA characteristics were analyzed.Results605 eligible RA pts were included. The average age of the population is 58.21 years. 72% of the patients are women. 21% are smokers and 65% are positive for anti-citrullinated protein antibody (ACPA) with a mean DAS28-CRP of 2.39 and a mean HAQ of 0.821. In 2020, 460 pts filled the questionnaire and 61% indicated they would receive the vaccine as soon as it is available. For the 179 pts (39%) who decline, the reasons for not having vaccine were no trust in the vaccine at this time (53%), fear of side effects (28%), opposition to vaccine (4%), previous SARS-CoV-2 infection (2%) and unknown (5%). Pts under the age of 50, women, low education grade, smokers, presence of RF/ACPA and treatment with a bioDMARD were less willing to receive the vaccine.In 2021, 538 pts were vaccinated and only 67 pts (11.1%) not. The majority received a mRNA vaccine (81.8%). 72 and 21 pts developed a SARS-CoV-2 infection before and after the vaccination, respectively. Among them, 5 were admitted to intensive care unit leading to 4 deaths. Only, 7 RA flares were observed and 17 pts switched the therapy. 101 adverse events were reported. All of them were mild and transient except 2 cases with pulmonary embolism and one case with Herpes Zooster infection.ConclusionThe SARS-COV-2 global pandemic is responsible of many medical dramas. In our RA cohort, we observed first hesitation followed by a high rate of vaccination. The safety was reassuring with a minimal number of RA flares and serious adverse events including only 4 deaths.AcknowledgementsThis work was supported by CAP48/RTBF.Disclosure of InterestsNone declared

POS0519 RELATIONSHIP BETWEEN DISEASE ACTIVITY AND MAJOR ADVERSE EVENTS IN PATIENTS WITH RHEUMATOID ARTHRITIS ON TOFACITINIB OR TNF INHIBITORS: A POST HOC ANALYSIS OF ORAL SURVEILLANCE

BackgroundUncontrolled rheumatoid arthritis (RA) activity and acute disease flares are associated with higher risk of adverse outcomes such as cardiovascular (CV) disease, venous thromboembolism (VTE), malignancy and infection.1-4ObjectivesTo evaluate associations of acute and cumulative Clinical Disease Activity Index (CDAI) measurements with major CV, malignancy, or infectious adverse events (AEs) of special interest in ORAL Surveillance.MethodsORAL Surveillance (NCT02092467) was a post-authorisation safety study of tofacitinib vs TNF inhibitors (TNFi) in patients (pts) aged ≥50 yrs with active RA despite methotrexate (MTX), and ≥1 additional CV risk factor. Pts were randomised 1:1:1 to tofacitinib 5 or 10 mg twice daily (BID) or subcutaneous TNFi. Two post hoc analyses were performed: (1) a time-varying multivariate Cox model examined risks of major AEs when pts were in CDAI-defined low (&gt;2.8–≤10; LDA), moderate (&gt;10–≤22; MDA) or high (&gt;22; HDA) disease activity vs remission (≤2.8). The Cox model also included pt demographics, medical history, RA characteristics, prior treatments, baseline (BL) medications and treatment arm, pre-selected using backward selection; (2) area under the curve (AUC) per yr for CDAI prior to event or to study end (pts without event) was calculated and compared using an analysis of variance model with treatment arm, event status and interaction (supportive). Nominal p values &lt;0.10 were considered evidence of associations.Results4362 pts were included. Mean RA duration at BL was approximately 10 yrs. All pts were on MTX at BL, and 28% had previously been on one other synthetic disease-modifying antirheumatic drug (DMARD). Overall, 10% of pts had been on one biologic DMARD. Hazard ratios suggested that when pts had LDA, MDA or HDA vs remission, they were potentially at higher risk of developing major adverse CV events (MACE), VTE and non-serious infections (NSIs) excluding herpes zoster (HZ), but not malignancies, serious infections or HZ (Figure 1). Similarly, mean CDAI AUC trended higher for MACE, VTE and NSIs (Table 1).Table 1.Cumulative CDAI (from BL to event) for pts with vs without events (AUC/yr)Major AEPts with eventsPts without eventsLS mean difference in pts with vs without eventsp valueTreatmentnLS mean AUC/yrnLS mean AUC/yrMACETofacitinib 5 mg BID426275.413364607.31668.10.0018*Tofacitinib 10 mg BID505237.413064482.6754.80.1253TNFi365234.513124851.5383.00.5069VTETofacitinib 5 mg BID156546.713634614.41932.30.0293*Tofacitinib 10 mg BID316688.213234458.52229.70.0003*TNFi86423.613394839.41584.10.1907Malignancy excl. NMSCTofacitinib 5 mg BID595249.313194618.9630.40.1655Tofacitinib 10 mg BID554793.713014482.2311.50.5077TNFi395561.413084826.3735.10.1854Serious infectionsTofacitinib 5 mg BID1275710.212424577.51132.70.0004*Tofacitinib 10 mg BID1505425.211974476.4948.80.0013*TNFi1056058.412404807.71250.70.0003*HZTofacitinib 5 mg BID1755184.511994738.1446.40.1101Tofacitinib 10 mg BID1635549.111864481.31067.80.0002*TNFi565667.212914875.5791.80.0930*NSIs excl. HZTofacitinib 5 mg BID7606608.34635122.51485.8&lt;0.0001*Tofacitinib 10 mg BID7506587.84265009.61578.2&lt;0.0001*TNFi7226737.65215217.51520.1&lt;0.0001**p&lt;0.10. Data collected after pts who were randomised to tofacitinib 10 mg BID had their dose reduced to 5 mg BID were included in the tofacitinib 10 mg BID group LS, least squares; n, number of pts in analysis of variance modelConclusionIn ORAL Surveillance, the risk of MACE, VTE and NSIs excluding HZ appeared higher when pts had active disease than when in remission. Greater cumulative RA disease activity was seen in pts who suffered these AEs vs those who did not. Our findings support treat-to-target recommendations for RA.

AB1346 ULTRASOUND ASSESSMENT OF SUB-CLINICAL HAND JOINT INFLAMMATION: A COMPARATIVE STUDY BETWEEN EARLY RHEUMATOID AND PSORIATIC ARTHRITIS

BackgroundUltrasound (US) detected subclinical inflammation can be present in early psoriatic arthritis (PsA) and rheumatoid arthritis (RA), and also in patients fulfilling clinical remission criteria[1-2]. Numerous evidences support that the persistence of subclinical synovitis detected by US is associated with a high risk of disease progression [2-3].ObjectivesTo evaluate sub-clinical inflammation of PsA and RA at the level of small joints of the hand and wrist by B-mode and Power Doppler US.Methods30 patients of early PsA and 35 patients of early RA (no clinical evidence of hand joint involvement, PsA disease duration &lt;2 years, and RA disease duration &lt;1 year) were recruited. US [grey scale (GS) and power Doppler (PD)] was performed to assess synovitis, tenosynovitis, joint effusion, and bone erosion of bilateral wrists, metacarpophalangeal joints, proximal and distal interphalangeal joints, as well as the flexor tendons and extensor compartments.ResultsA total of 35 patients were included in the RA group, including 10 males and 25 females. A total of 30 patients were included in the PsA group, including 12 males and 18 females. There were no significant differences in gender composition, age, and duration of disease between the two groups (P&gt;0.05) (Table 1). 19 (63.33%) PsA patients and 16 (45.71%) RA patients had sub-clinical hand joint synovitis. At the joint level, wrist joints were most commonly involved (23.08%), followed by MCP3 (15.38%) and DIP3 (13.46%) in PsA group. In RA group, wrist joints were most commonly involved (55.17%), followed by MCP3 (12.41%), and MCP2 (11.03%). Eight (26.67%) PsA patients and 16 (45.71%) RA patients were detected tenosynovitis. Tenosynovitis was most frequently presented at the extensor tendons in RA and at the flexor tendons in PsA patients (p&lt;0.05). The two most commonly affected were the 4th and 1st extensor compartments in RA patients, and the flexor pollicis longus and flexor digitorum profundus in PsA patients. 81 (6.80%) joint recesses in the RA and 75 (7.35%) joint recesses in PsA were detected effusion. Joint effusion was most frequently detected at radiocarpal and midcarpal joints in RA (30.86%, 25.92%, respectively). Effusion in PsA was most commonly presented at the 3rd PIP joints (26.67%), followed by radiocarpal joints (24.00%). Bone erosions were uncommon, totally 2 (6.67%) PsA patients and 3 (8.57%) RA patients were detected bone erosions.Table 1.Demographic characteristics of RA and PsA patientsRA (n=35)PsA (n=30)PFemale, n(%)25 (71.43%)18 (60.00%)0.33Age, years, mean±SD53.20±14.5054.23±13.650.77Disease duration, years, mean±SD0.72±0.370.91±0.530.07ConclusionThere are significant differences in the US findings of sub-clinical inflammation at the hand and wrist joints, such as the joint effusion and tenosynovitis, which may assist the identification between early RA and PsA. Simultaneously, it should be pointed out that there are some similarities in the joint involvement of sub-clinical synovitis between RA and PsA, physicians should take this into account in clinical work.Figure 1.Gray scale ultrasound sagittal view shows synovitis at the wrist joint in an RA patient (A) and at MCP3 in a PsA patient.

Assessment of the association between TNIP1 polymorphism with clinical features and risk of systemic lupus erythematosus.

Over the past decades, TNIP1 has been identified as a strong risk locus in multiple genome-wide association studies (GWAS), spanning multiple populations and various autoimmune diseases. TNIP1 is a polyubiquitin-binding protein that works as a physiological inhibitor of NF-κB and maintains immune homeostasis. Some studies have confirmed that TNIP1 is downregulated in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In the current study, for the first time, we evaluated the possible association between rs6889239 polymorphism in the TNIP1 gene with the risk and clinical characteristics of RA and SLE in the Iranian population. In this case-control study, 115 patients with RA, 115 patients with SLE, and 115 unrelated healthy subjects were enrolled to estimate rs6889239 genotypes with real-time PCR high resolution melting (HRM) method. Our results demonstrated considerable associations between CC genotype and C allele of rs6889239 with augmented risk of SLE (OR for CC genotype= 2.23; 95%CI [1.175-4.307], OR for C allele= 1.84; 95%CI [1.254-2.720]). However, there was an insignificant association between genotypes and allele frequencies of rs6889239 with the occurrence risk of RA in the population under study (p > 0.05). Additionally, stratification analysis specified that the C allele in rs6889239 was linked with the incidence of renal involvement in SLE patients and lower age of onset in the RA group (p < 0.05). These findings propose a significant association between TNIP1 polymorphism and higher risk of SLE and some clinical characteristics of RA and SLE.