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

ID PMID Title PublicationDate abstract
32324126 Effectiveness and safety of biologic and targeted synthetic disease-modifying anti-rheumat 2021 Mar OBJECTIVES: We aimed to evaluate the clinical outcomes and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and to identify predictors of treatment responses to b/tsDMARDs in elderly patients with rheumatoid arthritis (RA). METHODS: Data from the nationwide cohort of elderly (≥ 65 years) patients enrolled in the KOBIO Registry were analysed. Clinical outcomes were assessed, including changes in the Simplified Disease Activity Index, after treatment. Adverse events and reasons for drug discontinuation were assessed. Multivariable logistic regression analyses were performed to determine which baseline variables affected treatment responses and adverse events (AE). RESULTS: Elderly patients treated with b/tsDMARDs (n=355) or conventional synthetic DMARDs (csDMARDs) (n=104) were included. The median age was 70 years and 77% were female. After 1 year, 63% of patients in the b/tsDMARD group and 68% in the csDMARD group achieved remission or low disease activity (LDA). Overall, 27% of patients in the b/tsDMARDs group and 24% in the csDMARDs group experienced AE. A total of 43.4% of patients on b/tsDMARDs discontinued therapy due to lack of effectiveness (27%), AE (34%), or other reasons (35%). The estimated median retention of b/tsDMARDs was 2.5 years. Male sex and non-exposure to tobacco at baseline were independent factors associated with achieving remission or LDA after 1 year. Interstitial lung disease (ILD) was the most prominent comorbidity associated with AE. CONCLUSIONS: Treatment with b/tsDMARDs is effective and well tolerated in elderly patients with RA; nonetheless, ILD is a key comorbidity that should be monitored carefully.
32039944 Impact of Chronic DMARD Therapy in Patients With Rheumatoid Arthritis Undergoing Surgery o 2020 Jul 1 STUDY DESIGN: A multi-centered retrospective review from five institutions. OBJECTIVE: The aim of this study was to determine whether continuing or withholding disease-modifying antirheumatoid drugs (DMARDs) in the perioperative period affect outcomes in rheumatoid arthritis (RA) patients undergoing arthrodesis at the craniovertebral junction SUMMARY OF BACKGROUND DATA.: RA is a chronic systemic inflammatory disease that affects the cervical spine and is treated with DMARDs. Some advocate withholding DMARDs in the perioperative period due to concern for the cytotoxic effects of these medications. However, the impact of DMARDs in the perioperative period is not well understood. METHODS: A multicenter retrospective study from five affiliated institutions was performed. Adult patients with RA on chronic DMARDs undergoing posterior arthrodesis of the craniovertebral junction (occipital-cervical or atlanto-axial arthrodesis) were identified. Patients were stratified based on whether DMARD therapy was continued (C group) or discontinued (DC group) in the perioperative period. The primary outcome was the need for reoperation and reason for reoperation. RESULTS: Thirty-nine patients met inclusion criteria, 19 in C group and 20 in DC group. Average follow-up time was 42 months. Four patients (three in DC group and one in C group) required reoperation. Two patients from the DC group required readmission secondary to RA flare-up. CONCLUSION: Our cohort of RA patients who underwent occipital-cervical and C1/C2 posterior arthrodesis showed no significant differences in surgical complications when DMARD therapy was continued or discontinued in the perioperative period. The decision to continue or discontinue DMARD therapy in the perioperative period is at the discretion of the treating physician, but we encourage physicians to counsel patients regarding this theoretical risk and their tolerance of the medications as well as the risk of RA flare-up. Factors such as overall health, disease burden, nutrition, bone quality, smoking status, and other comorbid conditions are likely to have a larger influence on perioperative complications. LEVEL OF EVIDENCE: 3.
32167241 Association of anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes 2020 May INTRODUCTION: The most common genetic risk factor for rheumatoid arthritis (RA) is human leucocyte antigen DRB1 (HLA-DRB1) shared epitope (SE). AIM: To investigate the relationship between anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), immunoglobulin (Ig)G, IgM and IgA and HLA-DRB1 SE among Egyptian patients with RA. METHODS: Serum levels of anti-CCP antibodies and RFIgG, RFIgM, RFIgA were assayed using enzyme-linked immunosorbent assay for 157 Egyptian RA patients and 150 healthy controls attending the outpatient clinics of National Research Center and Kasr El Aini Hospital. HLA-DRB1 genotyping was performed by the DynalAllSetTM polymerase chain reaction (PCR) single specific primer low-resolution typing kits. Amplified PCR product was checked using 3% agarose gel. RESULTS: HLA-DRB1-SE was found among 129 (82.2%) RA patients and 67 (44.7%) controls (odds ratio [OR] 5.7, CI 3.4-9.6, P < .0001). The risk of RA development was higher with the presence of SE two alleles (OR 11.6, P < .0001), while the OR for 1 copy SE allele was 4.4 (P < .0001). HLA-DRB1-SE was significantly associated with positive as well as negative anti-CCP and RF isotypes. The stronger association was with anti-CCP positivity with OR 11 (5.1-23.6), P < .0001. Furthermore, the risk of development of positive anti-CCP and RF isotypes was higher with the presence of 2 copies of SE alleles than with 1 copy. CONCLUSION: The prevalence of HLA-DRB1-SE is high in Egyptian RA patients. The role of SE in RA patients is most probably related to the development of anti-CCP positive RA rather than the development of anti-CCP positivity.
32500745 Using pharmacogenetics to predict methotrexate response in rheumatoid arthritis patients. 2020 Jul INTRODUCTION: Methotrexate (MTX) is a folate antagonist and a first-line drug for the treatment of rheumatoid arthritis (RA). However, in up to 30% of cases, MTX monotherapy is insufficient, while a further 30% of patients suffer with severe adverse effects. Despite extensive clinical evidence, it is not currently possible to predict therapy outcomes and drug toxicity for MTX. Therefore, to establish biomarkers of toxicity and successful disease remission, pharmacogenomic approaches are rapidly becoming more popular. AREAS: This review summarizes recent pharmacogenomic studies evaluating MTX efficacy and toxicity. In recent years, multiple genetic alterations associated with MTX therapy outcomes and toxicity have been identified in genes associated with MTX metabolism and effector pathways. However, the data are inconsistent and require further validation. EXPERT OPINION: To date, several single nucleotide polymorphisms (SNPs) have been linked with MTX efficacy. However, thanks to equivocal data, pharmacogenomic testing in routine clinical practice remains a distant prospect. Genome-wide association studies (GWAS) could facilitate the evaluation of current SNPs, and support searches for new genetic variations Once achieved, only then will it be possible to introduce more personalized and individualized therapies for RA patients.
32356018 The Use of Collagen-Induced Arthritis Animal Model on Studying Bone Metabolism. 2020 Aug CIA is a well-studied animal model of autoimmune arthritis. It resembles rheumatoid arthritis as far as histopathological changes and molecular pathogenesis are concerned. CIA is induced by immunization with collagen type II in susceptible strains. The purpose of this review is to assess the use of CIA animal model on bone metabolism and the potential therapeutic agents that could reverse this effect. A database search from their inception to 2019 was conducted to identify experimental animal studies pertinent to CIA model and bone examination. Studies including ovariectomy or without a direct comparison between control and CIA groups were excluded. Forty-eight articles were considered suitable for inclusion. Imaging techniques, biomechanical analysis, histopathological studies, and molecular biology techniques were employed. A decrease in bone mineral density in CII arthritic animals was established. Bone loss was either periarticular, generalized or both. Although trabecular bone loss was clear, the effect on cortical bone is yet to be determined. The proposed mechanism is an imbalance between bone formation and resorption as a result of osteoclast activation. The signal pathways implicated appear to be the RANKL/RANK/OPG and the Wnt pathway. Many therapeutic targets were investigated with promising results.
31950339 Therapeutic Potential of Mesenchymal Stromal Stem Cells in Rheumatoid Arthritis: a Systema 2020 Apr Standard treatment options for rheumatoid arthritis (RA) often fail to deliver a long-term therapeutic outcome and in many cases cause intractable adverse events leading to treatment discontinuation or readjustment. Treatment with mesenchymal stem cells (MSCs) has been recently studied in RA due to its immunomodulatory and anti-inflammatory capacities. Thus, this study aims at systematically search and review the literature for randomized or non-randomized clinical trials comparing interventions of MSCs with placebo in RA patients. Electronic searches were conducted on PubMed, SCOPUS, Cochrane-CENTRAL, registries of clinical trials and grey literature. Selected studies were estimated for risk of bias with the Cochrane RoB tool 2 or the ROBINS-I tool. Four trials met the eligibility criteria and entered the review process. Identified MSCs treatments varied from allogeneic to autologous or umbilical cord-derived cells. Enrolled patients had an active RA and had poor responses to previous standard medications. In general, the safety evaluation revealed that treatment with MSCs was safe and well tolerated. Regarding the efficacy measurements, modest improvements were found in RA symptoms and RA-related indices. Significant decreases were found in inflammatory molecules such as C-reactive protein, tumor necrosis factor alpha and interleukin 6. However, clinical response criteria related to RA were achieved by a low-to-moderate percentage of patients. In conclusion, treatment of RA with MSCs appears to have a short-term therapeutic effect. Better-designed randomized trials with sufficient follow-up periods are needed so that the long-term safety and efficacy interventions with MSCs would be elucidated.
32356228 Anti-cyclic citrullinated peptide antibody in the cerebrospinal fluid in patients with rhe 2020 Aug Central nervous system (CNS) involvement, including encephalopathy, encephalitis, leptomeningitis, and pachymeningitis, in rheumatoid arthritis (RA) is rather rare. We report the case of a 61-year-old female with a history of RA in remission for 7 years, who presented with numbness, weakness of the left upper limb, dysarthria, and headache. Magnetic resonance imaging (MRI) of the brain showed meningeal enhancement in the frontal, parietal, and temporal lobes. Cerebrospinal fluid (CSF) examination detected high levels of both rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA), with a high ACPA-immunoglobulin G index (> 2.0). She was diagnosed with rheumatoid meningitis. Following combined therapy with oral prednisolone and intravenous infusion of cyclophosphamide, her symptoms promptly improved. After treatment, RF and ACPA levels in the CSF were reduced, and MRI showed improvement of the meningeal structures. This case, along with existing literature, suggests that the ACPA level in the CSF may serve as a useful marker for diagnosing of CNS involvement in RA, as well as an index of effectiveness of the associated treatment.
33338002 Good pain, bad pain: illness perception and physician attitudes towards rheumatoid arthrit 2021 May OBJECTIVES: Rheumatoid arthritis (RA) and fibromyalgia syndrome (FM) are common diagnoses encountered in rheumatology practice, but do not enjoy the same status. We aimed to examine physician's illness perceptions regarding these two rheumatologic disorders and to evaluate how they correlate with their relationship with these patients. METHODS: Forty-five rheumatologists were enrolled in the study. Demographic data were registered. Measures collected included the Brief Illness Perception Questionnaire (BIPQ) and the Difficult Doctor- Patient Relation Questionnaire (DDPRQ-10). Both were recorded twice, related to FM and RA. Empathy and burnout were also assessed. RESULTS: Of 45 physicians included in the study, only 53% were willing to accept FM patients. FM was considered a more severe disease than RA (FM-BIPQ mean score 54, SD 5.5 versus RA-BIPQ mean 45.6 SD 6.5, p<0.00) in terms of treatment control, understanding and emotional response generated by the disease. Doctor-patient relationship was perceived more difficult with FM patients compared to RA patients (FM-DDPRQ mean score 35.1, SD 9.2 versus RA-DDPRQ mean 19.6, SD 7.1, p<0.00), and was significantly correlated to the patient's concern about the illness (p<0.034) and patient's emotional response (p<0.036). Resistance to accept FM patients was largely influenced by difficult doctor-patient relationship. Higher levels of empathy were found in physicians experiencing less difficulty with FM patients. CONCLUSIONS: FM patients were perceived as more difficult than RA patients, with a high level of concern and emotional response. A high proportion of physicians were reluctant to accept them because they feel emotional/psychological difficulties meeting and coping with these patients.
31665481 What do we measure with 28-joint DAS in elderly patients? An explorative analysis in the N 2020 Jul 1 OBJECTIVE: Insight into the influence of ageing on disease outcomes is limited. The objective of this study was to examine the potential effect of age on disease activity using the 28-joint DAS (DAS28) and its components in patients with RA. METHODS: Baseline data of DMARD-naïve patients with RA from the Norwegian Register of DMARDs were used. Linear regression explored the strength of the association between age (<45, 45-65 and >65 years) and each DAS28 component while accounting for education and gender. Adjusted predicted scores for DAS28 components and total DAS28 score were calculated for each age category. RESULTS: Baseline data from 2037 patients [mean age 55.2 years (s.d. 14.0), 68% females] were available. Regression models had to be stratified for gender (P for interaction <0.001); education was a significant covariate. Males >65 years of age with an intermediate level of education have a 56% higher ESR and 25% higher 28-joint swollen joint count as compared with their younger counterparts (<45 years). For females, corresponding differences were 51% and 27%, respectively. The age effect on the 28-joint tender joint count and patient global assessment was negligible. In patients with an intermediate education level, DAS28 was 5.0 vs 5.5 (10% increase) in the youngest vs oldest age groups, independent of gender. CONCLUSION: The age-related increase in ESR and 28-joint swollen joint count scores without a relevant corresponding increase in 28-joint tender joint count and patient global assessment might imply that age-related processes (e.g. soft tissue changes, physiological ESR increase) contribute to a higher DAS28 in elderly patients.
32690328 Subclinical inflammation in the preclinical phase of rheumatoid arthritis might contribute 2020 Dec The first degree relatives of rheumatoid arthritis (RA) patients have a higher risk of developing RA, which is related to the expression of autoantibodies against citrullinated proteins (ACPA). Remarkably, prior to the onset of RA, cartilage damage is already initiated, whereas ACPA autoantibodies are already expressed. Here we show that both TNF-α and IL-6 are also increased prior to the onset of RA. Furthermore, when the levels of DKK1 and Sclerostin were evaluated in first degree relatives of RA patients, we found that the serum levels of TNF- α correlate with the expression levels of both DKK1 and Sclerostin. Interestingly, when the disease is already established, the correlation of TNF- α with DKK1 is lost in RA patients, whereas the correlation of Sclerostin with both TNF- α and IL-6 is further increased. Our data suggest a subclinical inflammation in patients at high risk of developing RA, which might lead to an increase in the levels of both DKK1 and Sclerostin, contributing to joint damage in the preclinical phase of the disease linked to the expression of ACPA autoantibodies.
33127857 Depression and anxiety in an early rheumatoid arthritis inception cohort. associations wit 2020 Oct OBJECTIVE: Depression and anxiety are not uncommon in Rheumatoid arthritis (RA). It is increasingly recognised that they are associated with high disease activity and worse disease outcomes. We aimed to examine the frequency of depression and anxiety in an early RA inception cohort and to explore associations with disease-related measures. METHODS: The Scottish Early Rheumatoid Arthritis inception cohort recruited newly diagnosed RA patients followed-up 6-monthly. Anxiety and depression were assessed using the hospital anxiety and depression scale. Associations with demographic characteristics and disease-related measures were examined at baseline, 6 months and 12 months. RESULTS: 848 RA patients were included. The prevalence of anxiety and depression at baseline was 19.0% and 12.2%, respectively. Depression and anxiety scores correlated with DAS28 at all time-points (all p<0.0001). In multivariable linear regression, anxiety score at baseline was associated with younger age and Health Assessment Questionnaire (HAQ) score. Anxiety scores at 6 months and 12 months were associated with low body mass index (BMI), baseline anxiety score and current patient global score and HAQ. Depression score at baseline was associated with younger age, being single and HAQ, while depression scores at 6 months and 12 months were associated with male gender (only at 6 months), baseline anxiety and depression scores and current patient global score, HAQ and C-reactive protein (CRP) levels. CONCLUSION: Depression and anxiety are associated with disease activity, worse functional status and other variables in early RA. There is a close relationship between CRP and depression but not anxiety.
31722413 An updated matrix to predict rapid radiographic progression of early rheumatoid arthritis 2020 Aug 1 OBJECTIVE: In early RA, some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Matrices predicting this risk have been proposed, lacking precision or inadequately calibrated. We developed a matrix to predict RRP with high precision and adequate calibration. METHODS: Post-hoc analysis by pooling individual data from cohorts (ESPOIR and Leuven cohorts) and clinical trials (ASPIRE, BeSt and SWEFOT trials). Adult DMARD-naïve patients with active early RA for which the first therapeutic strategy after inclusion was to prescribe methotrexate or leflunomide were included. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve. Calibration and discriminatory power of the model were checked. The probabilities of RRP for each combination of levels of baseline characteristics were estimated. RESULTS: 1306 patients were pooled. 20.6% exhibited RRP. Four predictors were retained: rheumatoid factor positivity, presence of at least one RA erosion on X-rays, CRP > 30mg/l, number of swollen joints. The matrix estimates RRP probability for 36 combinations of level of baseline characteristics with a greatly enhanced precision compared with previously published matrices (95% CI: from ± 0.02 minimum to ± 0.08 maximum) and model calibration is excellent (P = 0.79). CONCLUSION: A matrix proposing RRP probability with high precision and excellent calibration in early RA was built. Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice.
33162300 Prevalence, risk factors and proteomic bioprofiles associated with heart failure in rheuma 2021 Mar BACKGROUND: Rheumatoid arthritis (RA) patients have high risk of heart failure (HF). AIMS: Identifying the risk factors and mechanistic pathways associated with HF in patients with RA. METHODS: Cohort study enrolling 355 RA patients. HF was defined according to the ESC criteria. 93 circulating protein-biomarkers (91CVDIIOlink®+troponin-T+c-reactive protein) were measured. Regression modeling (multivariate and multivariable) were built and network analyses were performed - based on the identified relevant protein biomarkers. RESULTS: 115 (32.4%) patients fulfilled the ESC criteria for HF, but only 24 (6.8%) had a prior HF diagnosis. Patients with HF were older (67 vs. 55yr), had a longer RA duration (10 vs. 14yr), had more frequently diabetes, hypertension, obesity, dyslipidemia, atrial fibrillation, and ischemic arterial disease. Several protein-biomarkers remained independently associated with HF, the top (FDR1%) were adrenomedullin, placenta-growth-factor, TNF-receptor-11A, and angiotensin-converting-enzyme-2. The networks underlying the expression of these biomarkers pointed towards congestion, apoptosis, inflammation, immune system signaling and RAAS activation as central determinants of HF in RA. Similar HF-associated biomarker-pathways were externally found in patients without RA. Having RA plus HF increased the risk of cardiovascular events compared to RA patients without RF; adjusted-HR (95%CI)=2.37 (1.07-5.30), p=0.034 CONCLUSION: Age, cardiovascular risk factors, and RA duration increase the HF odds in patients with RA. Few RA patients had a correct prior HF diagnosis, but the presence of HF increased the patients` risk. RA patients with HF largely share the mechanistic pathways of HF patients without RA. Randomized HF trials should include patients with RA. CLINICALTRIALS. GOV ID: NCT03960515.
33074413 Pro-inflammatory cytokine response pre-dominates immuno-genetic pathway in development of 2020 Nov Rheumatoid arthritis (RA) is a crucial inflammatory joint disease characterized by loss of self-tolerance and severe cartilage loss, autoimmune, and subchondral bone erosions. Cytokines are the key regulators of inflammatory responses. Homeostatic imbalances in pro- and anti-inflammatory cytokine activities can result in pathogenic inflammatory reactions. These imbalances could be initiated by environmental factors but the ability to define the threshold of environmental impact relies on the genetic background of the pro- and anti-inflammatory cytokines. To address this a case-control association study was carried out in 429 individuals from Malayalam speaking ethnic population from South India. Functionally relevant SNPs from IL-10, IL-6, IL-1β and IL-1RN were genotyped using PCR -RFLP and sequencing. Meta-analysis was performed for the associated variants of IL-10, IL-1β. Significant association with RA was observed with IL-1β rs1143634, rs1143627, IL-10 rs1800896, IL-6 rs1800796, rs1800797. The associated SNPs are likely to impact transcriptional activity of a gene. Meta-analysis with global populations also provide evidence that IL-10 and IL-1β could be a global marker for RA. The functional significance of associated risk variants of IL-1β and IL-6 indicate increased production of the pro-inflammatory cytokines while IL-10 risk allele suggest reduced production of anti- inflammatory cytokines. The study concludes that increased production of pro-inflammatory cytokines and reduced production of anti- inflammatory cytokines may influence the Th1/Th2 equilibrium resulting in a triggering of Th1 mediated inflammatory responses in development of RA.
32205568 Future use of musculoskeletal ultrasonography and magnetic resonance imaging in rheumatoid 2020 May PURPOSE OF REVIEW: Musculoskeletal ultrasonography (MSUS) and magnetic resonance imaging (MRI) play important roles in diagnosis, monitoring, and prognostication of rheumatoid arthritis. This review highlights recent literature in this field and aims to provide insight into the future use in clinical practice. RECENT FINDINGS: Recent studies concerning the use of MSUS and MRI in clinical practice show how MSUS and MRI can improve diagnosis and monitoring of rheumatoid arthritis and how they can predict both radiographic progression and clinical outcome (e.g., successful tapering of medical treatment). Moreover, novel technical developments of the two imaging modalities, such as 3D ultrasonography, ultrasound image reading with convolutional neural network, image fusion (MSUS and MRI) and whole-body MRI show promising results. Further validation of these novel techniques is required prior to implementation. SUMMARY: MSUS and MRI will be important parts of the future management of rheumatoid arthritis patients, mostly because of their ability to detect rheumatoid arthritis changes at a very early stage and to predict the course of disease. However, the exact role in routine clinical practice is still to be defined.
31475852 A large observational cohort study of rheumatoid arthritis, IORRA: Providing context for t 2020 Jan Real-world evidence, based on real-world data from routine clinical treatment, is becoming increasingly important for providing high-quality medical care. Large-scale cohort studies can provide useful access to some of this real-world evidence, as shown by the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) cohort in Japan. This large cohort study of patients with rheumatoid arthritis (RA) has been surveying enrolled participants since its inception in 2000. In the last 19 years, it has served as a database for a wide range of research in areas including transitions in medical care at the clinical level, changes in therapeutic drugs, approaches to comorbidities, developments in pharmacoeconomics, and the effects of genomic information on treatment options. This research has resulted in the publication of 133 articles in English to date. IORRA monitors changes in the management of RA, and has quantified over time the daily experience of clinicians who provide routine medical care. Such observational databases, which reflect the reality of daily clinical practice, will become increasingly important and may provide a model for similar research in other disease areas.
31531708 Oral health and orofacial function in patients with rheumatoid arthritis. 2020 Mar The aim of the study was to describe the oral health and orofacial function of Mexican patients with rheumatoid arthritis (RA) and their association with clinical and radiological aspects of the disease. Patients with RA received a complete odontological exam, which also included a clinical and radiographic assessment of the temporomandibular joint (TMJ). The rheumatologic assessment included detailed profiling of the disease and serological and radiographic parameters. The study included 62 RA patients; the median (min-max) age was 51 (18-72) years old and 8.5 (1-39) years of disease duration. The 63.6% of the patients had DAS28 ≥ 3.2, and a median (min-max) of Sharp/van der Heijde score (SvdHS) of 41 (0-214). 98.3% of the patients presented caries, which were severe in 53.3% of the cases. The 73.8% of the patients were missing teeth due to caries, with a median (min-max) of 4 (0-32) teeth missing per patient. Oral hygiene was classified as bad in 49.1% of patients and only 15.3% of them had a healthy periodontium. The TMJ function was abnormal in 98.4% of the patients and 62.9% of them presented moderate or severe TMJ disorder (TMD). The radiographic damage of the TMJ correlated positively with the SvdHS. No correlations were found between disease activity or structural progression and orofacial variables, including periodontitis. There are severe oral and orofacial health problems in RA patients despite having medical attention for their disease. Multidisciplinary management remains an area of opportunity for both the medical specialists and the health system in our country.
31830775 Effect of biologics in the level of cytokines in the synovial fluid of patients with ankyl 2020 Mar BACKGROUND/AIMS: Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. METHODS: Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. RESULTS: The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. CONCLUSION: Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.
32187055 Involvement of long non-coding RNAs in the pathogenesis of rheumatoid arthritis. 2020 Apr 20 Long non-coding RNA (lncRNA) plays a contributory role in rheumatoid arthritis (RA). In this review, we summarized the current findings of lncRNAs in RA, including cellular function and the potential mechanisms. Serum lncRNA levels are associated with serum proinflammatory cytokines and disease activity. LncRNAs regulate proliferation, migration, invasion and apoptosis of RA fibroblast-like synoviocytes (FLSs), modulate the differentiation of T lymphocytes and macrophages, and affect bone formation-destruction balance of chondrocytes. Besides, lncRNAs are involved in inflammation and cell motivation signaling pathways. In-depth research on lncRNAs may help elucidate the pathogenesis of RA and provides clues for novel treatment targets.
30789096 Anti-cyclic citrullinated peptide antibody titers decrease in rheumatoid arthritis patient 2020 Mar Objectives: To analyze the effects of tocilizumab on peripheral B-cell subpopulation and its ability to produce anti-cyclic citrullinated peptide (CCP) antibody in patients with rheumatoid arthritis (RA).Methods: Thirteen consecutive RA patients initiated with tocilizumab were enrolled in our prospective study. Anti-CCP antibody titers and clinical parameters were evaluated during treatment. Peripheral blood B-cell subsets were analyzed using flow cytometry according to the Human Immunology Project.Results: Disease activity was significantly improved and anti-CCP antibody titers significantly decreased at week 24 compared to baseline. The percentages of post-switch memory B cells in CD19+ cells transiently increased at week 12, but there was no significant difference in any of the investigated B-cell subpopulations at week 24 compared to baseline. The ratios of post-switch memory to naïve B cells (post-switch/naïve) correlated negatively with anti-CCP antibody titers regardless of the time-points.Conclusion: Our study indicated that tocilizumab has a potential to reduce anti-CCP antibody production presumably by affecting post-switch/naïve ratio, and that anti-CCP antibody titers reflect B-cell distribution/subpopulation. As anti-CCP antibodies are produced in lymph nodes or ectopic lymphoid structures in synovial tissues, not in circulation, transient increment of post-switch memory B cells after tocilizumab treatment may reflect the altered balance of B-cell distribution between circulation and arthritic joints, resulting in suppressed production of anti-CCP antibody in situ.