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ID PMID Title PublicationDate abstract
34450118 The role for JAK inhibitors in the treatment of immune-mediated rheumatic and related cond 2021 Oct JAK inhibitors (JAKIs) are a new class of targeted therapy that have entered clinical practice for the treatment of immune-mediated rheumatic conditions. JAKIs can block the signaling activity of a variety of proinflammatory cytokines and therefore have the potential to mediate therapeutic benefits across a wide range of immune-mediated conditions. Several JAKIs are licensed, and many more are undergoing clinical trials. Here we provide a narrative review of the current and upcoming JAKIs for adult immune-mediated rheumatic and related conditions, with a specific focus on efficacy in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, psoriasis, and inflammatory bowel disease. The overall safety profile of JAKIs appears largely comparable to that of existing biologic cytokine-targeting agents, particularly, TNF inhibitors, apart from risk of herpes zoster, which is increased for JAKIs. Importantly however, unresolved safety concerns remain, particularly relating to increased venous thromboembolism.
33664742 Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumat 2021 Rheumatoid arthritis (RA) is an autoimmune disease. Fibroblast-like synoviocytes (FLS) serve a major role in synovial hyperplasia and inflammation in RA. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, shows promising therapeutic effects for RA and is now in phase II clinical trials in China. However, the underlying mechanism of LLDT-8 is still not fully understood. Here, we found that LLDT-8 inhibited proliferation and invasion of RA FLS, as well as the production of cytokines. Microarray data demonstrated that LLDT-8 upregulated the expression of long non-coding RNA (lncRNA) WAKMAR2, which was negatively associated with proliferation and invasion of RA FLS, as well as the production of pro-inflammatory cytokines. Knockdown of WAKMAR2 abolished the inhibitory effects of LLDT-8 on RA FLS. Mechanistically, WAKMAR2 sponged miR-4478, which targeted E2F1 and downstreamed p53 signaling. Rescue experiments indicated that the inhibitory effects of LLDT-8 on RA FLS were dependent on WAKMAR2/miR-4478/E2F1/p53 axis.
34132890 Tele-health interventions to support self-management in adults with rheumatoid arthritis: 2021 Aug Rheumatoid arthritis (RA), a long-term auto-immune condition is a challenging condition for patients to manage. Goals of treatment include reducing pain, decreasing inflammation, and improving an individual's overall function. Increasingly technology is being utilised to support patients to self-manage their condition. The aim of this systematic narrative review was to synthesise and critically appraise published evidence concerning the effectiveness of tele-health interventions to support self-management in RA. Bibliographic databases searched from 2014 to March 2020 included MedLINE, Embase, Cochrane Library. Search strategy combined the following concepts: (1) rheumatoid arthritis, (2) tele-health interventions, and (3) self-management. Only randomised controlled trials (RCTs) involving adults with RA were included. Titles, abstracts, full-text articles were screened, any discrepancies were checked by a second reviewer. Risk of bias was assessed using Cochrane risk of bias tool and data were extracted utilising the Cochrane data collection form for RCT interventions along with the TiDier checklist. Due to high heterogeneity, results were not meta-analysed and instead data were synthesised narratively. The search identified 98 articles, seven were included. The completed RCTs varied in the nature of the interventions, duration/severity of RA, outcomes measured and effectiveness of the interventions. The completed RCTs included a total of 791 participants Disease duration was largely between 4 and 10 years and disease severity on average was moderate. There was extensive variation in intervention components, theories underpinning theories and outcomes measured. Five RCTs reported a positive effect on factors such as disease activity, medication adherence, physical activity and self-efficacy levels. This study suggests that tele-health interventions that are well-designed, tailored and multi-faceted can help to achieve positive self-management outcomes in RA. None of the studies showed evidence of harm.
33864158 High disease relapse after bDMARD spacing in psoriatic arthritis compared to rheumatoid ar 2021 Sep The objective is to evaluate the effectiveness of a spacing strategy of bDMARDs in a cohort of selected patients in disease remission or low-disease activity (LDA) without glucocorticoids affected with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). This was a single-centre study carried out on patients prospectively enrolled in the biologic Apulian registry. Patients whose disease was in remission or LDA without taking glucocorticoids during the previous 6 months and who had agreed to increase the time interval between bDMARD doses were included in this study. Demographic and clinical characteristics were recorded at baseline and at 3, 6 and 12 months of follow-up. Endpoint of the study was the survival of spacing doses in the time lag of the study. Failure of spacing was defined as the first flare of disease. Thirty-seven RA, 28 PsA and 20 axSpA patients underwent bDMARD spacing according to a local strategy. During the follow-up, 5 RA, 6 PsA and 4 axSpA patients had a joint flare, but further 5 PsA patients manifested a skin relapse. Global persistence was 86.5% for RA (MST = 41 (95% CI: 37-45) months) and 80% for axSpA patients (MST = 36 (95% CI: 31-42) months). PsA patients showed a lower persistence, being of 60.7% (MST = 30 (95% CI: 23-36) months) (log-rank test, p = 0.03). Dose reduction by spacing bDMARD doses may be a feasible approach in patients with persistent remission/LDA activity. However, PsA patients might have greater odds of spacing failure because of skin psoriasis relapse. Key Points • Spacing of bDMARDs may be a feasible strategy for some patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis who achieve the target and withdrawn glucocorticoids. • Psoriatic arthritis patients showed lower persistence because of both articular and skin relapses.
33568191 Which patient-reported outcomes do rheumatology patients find important to track digitally 2021 Feb 10 BACKGROUND: Patient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management. METHODS: Adult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure. RESULTS: Among pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1-3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient's preferences regarding the importance of these PROs were stable over time. CONCLUSION: The symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.
33333232 An updated advance of autoantibodies in autoimmune diseases. 2021 Feb Autoantibodies are abnormal antibodies which are generated by pathogenic B cells when targeting an individual's own tissue. Autoantibodies have been identified as a symbol of autoimmune disorders and are frequently considered a clinical marker of these disorders. Autoimmune diseases, including system lupus erythematosus and rheumatoid arthritis, consist of a series of disorders that share some similarities and differences. They are characterized by chronic, systemic, excessive immune activation and inflammation and involve in almost all body tissues. Autoimmune diseases occur more frequently in women than men due to hormonal impacts. In this review we systemically introduce and summarize the latest advances of various autoantibodies in multiple autoimmune diseases.
34768991 Methotrexate Alters the Expression of microRNA in Fibroblast-like Synovial Cells in Rheuma 2021 Oct 26 We aimed to investigate the effect of methotrexate (MTX) on microRNA modulation in rheumatoid arthritis fibroblast-like synovial cells (RA-FLS). RA-FLS were treated with MTX for 48 h. We then performed miRNA array analysis to investigate differentially expressed miRNAs. Transfection with miR-877-3p precursor and inhibitor were used to investigate the functional role of miR-877-3p in RA-FLS. Gene ontology analysis was used to investigate the cellular processes involving miR-877-3p. The production of cytokines/chemokines was screened by multiplex cytokine/chemokine bead assay and confirmed by ELISA and quantitative real-time PCR. The migratory and proliferative activities of RA-FLS were analyzed by wound healing assay and MKI-67 expression. MTX treatment altered the expression of 13 miRNAs (seven were upregulated and six were downregulated). Among them, quantitative real-time PCR confirmed that miR-877-3p was upregulated in response to MTX (1.79 ± 0.46-fold, p < 0.05). The possible target genes of miR-877-3p in RA-FLS revealed by the microarray analysis were correlated with biological processes. The overexpression of miR-877-3p decreased the production of GM-CSF and CCL3, and the overexpression of miR-877-3p inhibited migratory and proliferative activity. MTX altered the miR-877-3p expression on RA-FLS, and this alteration of miR-877-3p attenuated the abundant production of cytokines/chemokines and proliferative property of RA-FLS.
33773523 Effects of the COVID-19 pandemic on psychology and disease activity in patients with ankyl 2021 Aug 30 BACKGROUND/AIM: The COVID-19 outbreak is known to increase stress levels of most patients with chronic diseases. Patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are highly susceptible to environmental stress. In the current study, we aimed to determine how the COVID-19 pandemic psychologically affected patients with chronic progressive diseases such as AS and RA and the effects of these psychological factors on disease activity. MATERIALS AND METHODS: Age and sex-matched patients with AS (n = 80), RA (n = 80), and healthy controls (n = 80) were included in the study. All participants were evaluated with the “Perceived COVID-19 Threat Form (PCTF)”, “Suicide-Ideation Scale (SIS)”, “Hospital Anxiety and Depression Scale (HADS)”, “The Ability to Cope with Trauma (PACT)”, and “Psychological General Well-Being Index (PGWB)” scales. BASDAI was used in patients with AS, and DAS28 was used in patients with RA to assess disease severity. RESULTS: Compared to healthy individuals, patients with RA and AS had lower PGWB scores and higher HADS depression and anxiety subscale scores. Almost all psychometric assessment test scores were worse in AS patients with high-disease activity compared to those in low-disease activity. PACT scores were higher in patients with moderate RA compared to patients with mild RA (p = 0.006). While a positive correlation was identified between BASDAI and most of the psychometric assessment test scores (r = 0 .36 for PCTF, r = 0.53 for depressive scores, r = 0.54 for anxiety scores, r = 0.57 for suicidal ideation), DAS28 scores were found to be associated only with PACT total and PACT perceived forward-focused subscale scores (r = –.26 and r = .33, respectively). CONCLUSION: Psychologically, AS and RA patients were found to be worse off compared to healthy controls. The perceived COVID threat and psychological status were associated with disease activity in AS, but not RA patients. Patients with chronic illnesses may be more vulnerable to the psychological effects of the pandemic, which can worsen disease activity.
33689246 [Connective tissue disease-related interstitial lung disease]. 2021 Mar 10 The connectivitides are autoimmune diseases that affect many organs. All of them can cause interstitial lung disease, the most frequent forms being the NSIP (nonspecific interstitial pneumonia) and the UIP (usual interstitial pneumonia). The best screening method is the high-resolution chest CT. The treatment of ILD includes glucocorticoids, immunosuppressive and antifibrotic agents, as well as non-pharmacological therapies. We present the screening and treatment algorithm for the ILD in systemic sclerosis, which is very well established. We also discuss the management of the ILD in rheumatoid arthritis, a very prevalent disease, and though of large public interest.
35462089 The Structural Index Score and its relation to foot function, disability and physical perf 2022 May OBJECTIVES: To evaluate the Structural Index Score (SIS) - a clinical foot deformity assessment index developed for RA, and to compare its results with foot function, disability and physical performance tests. METHODS: In this cross-sectional study, 104 patients with foot pain were evaluated according to SIS score, subscales (Forefoot SIS and Rearfoot SIS) and items. Results were compared with the Foot Function Index (FFI), the Health Assessment Questionnaire Disability Index (using lower limbs items: LL-HAQ), and physical performance tests: Berg Balance Scale (BBS), the Timed Up and Go test (TUG) and the 5-Time Sit down-to-Stand up Test (SST5). RESULTS: There was a weak correlation of SIS score with FFI and LL-HAQ. Rearfoot SIS was correlated with FFI, LL-HAQ and worse performance in BBS, TUG and SST5. Regarding Rearfoot SIS items, the ankle ROM was correlated to all studied outcomes, the calcaneus varus/valgus was correlated with FFI (total, pain and disability subscales) and the planus/cavus deformity with FFI-pain, HAQ-DI and LL-HAQ. Forefoot SIS did not correlate with any outcome measures. In relation to Forefoot SIS items, hallux valgus was associated with foot function (FFI-total, pain and disability subscales), the MTPs joints subluxation was correlated with FFI-disability subscale, and the 5th MTP exostosis was associated with FFI-pain. CONCLUSION: SIS score was correlated to impaired foot function (FFI) and disability (LL-HAQ). Rearfoot SIS was correlated to worse performance on FFI, LL-HAQ, BBS, TUG and SST5. SIS score index can be a useful tool to evaluate the rheumatoid foot deformities, but a better graduation of foot deformities should add sensitivity to this method.
34607227 The monomer derivative of paeoniflorin inhibits macrophage pyroptosis via regulating TLR4/ 2021 Dec OBJECTIVE: This study was aimed to investigate the effect of monomer derivative of paeoniflorin (MDP) on macrophage pyroptosis mediated by TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis (AA) rats. METHOD: Wistar rats were divided into normal group, AA model group, MDP (50 mg/kg) group and MTX (0.5 mg/kg) group. The expression of TLR4, NLRP3 and GSDMD in macrophage were detected by immunofluorescence assay. The expression of TLR4 and the ratio of macrophage pyroptosis were analyzed by flow cytometry. Cell morphology was observed by scanning electron microscopy. The cytokine levels of IL-18 and IL-1β were detected by ELISA. The expressions of proteins related to macrophage pyroptosis were detected by western blot. RESULTS: MDP has a therapeutic effect on rats AA by reducing the secondary inflammation and improving pathological changes. The results of X-ray imaging and ultrasound images showed that MDP could inhibit bone erosion, soft tissue swelling, and joint space narrowing. Macrophage pyroptosis was found in secondary inflammation of AA rats. The expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in macrophage were increased, the levels of IL-18 and IL-1β were enhanced, and the morphology of pyroptosis could be observed. MDP could inhibit macrophage polarization and macrophage pyroptosis, and down-regulated the cytokine levels of IL-18 and IL-1β in AA rats. MDP could regulate the M1/M2 ratio, decreased the ratio of macrophage pyroptosis and down-regulated the expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in vivo and in vitro. CONCLUSION: Abnormal activation of TLR4/NLRP3/GSDMD signaling pathway may be involved in macrophage pyroptosis in AA rats. The therapeutic effect of MDP on AA rats is related to the inhibition of macrophage pyroptosis by regulating the TLR4/NLRP3/GSDMD signaling pathway.
33386901 The feasibility of an exercise intervention to improve sleep (time, quality and disturbanc 2021 Feb Current rheumatology guidelines recommend exercise as a key component in the management of people with RA, however, what is lacking is evidence on its impact on sleep. Objective is to assess the feasibility of a walking-based intervention on TST, sleep quality, and sleep disturbance and to generate potential effect size estimates for a main trial. Participants were recruited at weekly rheumatology clinics and through social media. Patients with RA were randomized to a walking-based intervention consisting of 28 sessions, spread over 8 weeks (2-5 times/week), with 1 per week being supervised by a physiotherapist, or to a control group who received verbal and written advice on the benefits of exercise. Primary outcomes were recruitment, retention, protocol adherence and participant experience. The study protocol was published and registered in ClinicalTrials.gov NCT03140995. One hundred and one (101) people were identified through clinics, 36 through social media. Of these, 24 met the eligibility criteria, with 20 randomized (18% recruitment; 100% female; mean age 57 (SD 7.3 years). Ten intervention participants (100%) and eight control participants (80%) completed final assessments, with both groups equivalent for all variables at baseline. Participants in the intervention group completed 87.5% of supervised sessions and 93% of unsupervised sessions. No serious adverse events were related to the intervention. Pittsburgh Sleep Quality Index global score showed a significant mean improvement between the exercise group-6.6 (SD 3.3) compared to the control group-0.25 (SD 1.1) (p = 0.012); Intervention was feasible, safe and highly acceptable to study participants, with those participants in the exercise group reporting improvements in sleep duration and sleep quality compared to the control group. Based on these findings, a fully powered randomized trial is recommended. Trial registration number: ClinicalTrials.gov Identifier: NCT03140995 (April 25th, 2017).
31758663 Treat-to-Target Approach in Rheumatoid Arthritis: A Quality Improvement Trial. 2021 Feb OBJECTIVE: Using a quality improvement approach, our objective was to integrate a treat-to-target approach for rheumatoid arthritis (RA) through routine electronic collection of patient-reported disease activity scores and a multidisciplinary learning collaborative for rheumatologists. METHODS: RA patients completed a patient-reported outcome measure, the Routine Assessment of Patient Index Data 3 (RAPID3), at check-in. Nine rheumatologists and their patients were allocated to a learning collaborative intervention group focused on a treat-to-target approach and 13 were allocated to a control group. The primary outcome was documentation of a treat-to-target implementation score: disease activity score, disease activity score used in the medication change decision, the presence of a treatment target, and an indication of shared decision-making. A primary analysis of patient visits with medication changes was conducted using an interrupted time-series analysis. RESULTS: We studied 554 individual rheumatology patients with 709 patient visits. Treat-to-target implementation scores among intervention rheumatologists (mean ± SD 44.6% ± 1.63%) were 12.4% higher than in the control group (mean ± SD 32.2% ± 1.50%; P < 0.0001). We observed differences in treat-to-target implementation score components, comparing intervention group to control group rheumatologists: disease activity score present, 77.2% versus 68.0% (P = 0.02); disease activity score used in the medication change decision, 45.2% versus 30.0% (P < 0.01); treatment target, 9.0% versus 0.4% (P < 0.01); and shared decision-making, 46.9% versus 30.0% (P < 0.01). Secondary analysis of patient visits with high RAPID3 scores found that medication changes were 54% less likely in the intervention versus control group (odds ratio 0.46 [95% confidence interval 0.27-0.79], P = 0.005). CONCLUSION: This nonrandomized, interrupted time-series trial demonstrated a modest but significant impact of a learning collaborative intervention on rheumatologist documentation of a treat-to-target approach in RA.
34299006 Disease Differentiation and Monitoring of Anti-TNF Treatment in Rheumatoid Arthritis and S 2021 Jul 9 Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are comprehensive immunological disorders. The treatment of these disorders is limited to ameliorating the symptoms and improving the quality of life of patients. In this study, serum samples from RA, AS, and PsA patients were analyzed with metabolomic tools employing the 1H NMR method in combination with univariate and multivariate analyses. The results obtained in this study showed that the changes in metabolites were the highest for AS > RA > PsA. The study demonstrated that the time until remission or until low disease activity is achieved is shortest (approximately three months) for AS, longer for RA and longest for PsA. The statistically common metabolite that was found to be negatively correlated with the healing processes of these disorders is ethanol, which may indicate the involvement of the gut microflora and/or the breakdown of malondialdehyde as a cell membrane lipid peroxide product.
33057973 Untying the correlation between apolipoproteins and rheumatoid arthritis. 2021 Jan AIM AND OBJECTIVE: The concentration of lipoproteins and apolipoprotein are extremely low in the synovial fluid of any healthy person as compared to the concentrations in plasma. However, in the synovial fluid of any diseased patient the amount of cholesterol and lipids is sharply increased. The current review defines the role of various apolipoproteins and lipoproteins and their constituent subfractions in the synovial fluid embarking its principal role in rheumatoid arthritis. It also explains the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins in synovial fluid. MATERIALS AND METHODS: Various research and review articles highlighting the role of apolipoproteins and lipoproteins were procured from medical websites mainly Pubmed, Medline, Science Direct, etc., and studied for the writing of the review paper. CONCLUSION: Mainly apolipoproteins A-1, B and E are prominently increased in chronic inflammatory joint disorders. Several theories have been proposed to understand the source of increase of lipids and apolipoproteins in synovial fluid of the diseased patients compared to healthy individuals, yet the precise mechanism is still not lucid. Lipoproteins are believed to play both functional role and pathological role in the synovial fluid. The activated T-lymphocytes in patients of RA lead to activation of inflammatory cytokines such as tumor necrosis factor and interleukins which embark to be the principal mechanism for induction of the disease. It can be thus concluded that the apolipoproteins prevent the activation of monocytes by blocking their contact of activation and thus play critical role in management of RA by inhibiting the production of proinflammatory cytokines.
33507129 The clinical value of serum sirtuin-1 in the diagnosis of rheumatoid arthritis: a pilot st 2021 Oct Introduction: Cell biology studies, animal models and other data suggest a role for sirtuin-1 in the pathogenesis of rheumatoid arthritis (RA). We hypothesized the clinical significance of serum sirtuin-1 in this disease.Methods: Serum was obtained from 141 RA patients, 144 non-RA patients and 88 healthy controls. Sirtuin-1, anti-mutant citrulline vimentin antibody (anti-MCV), anti-cyclic citrulline polypeptide antibody (anti-CCP), rheumatoid factor and C-reactive protein were measured by immunological methods, and erythrocyte sedimentation rate was determined by the Westergren method.Results: All markers were higher in the RA group than in the non-RA group and the healthy control group (P < 0.01). The specificity of sirtuin-1 for the diagnosis of RA was 97% (the highest among all markers), sensitivity was 71%. In ROC curve analysis, the AUCs (95% CI) of sirtuin-1, anti-CCP and anti-MCV were 0.87 (0.82-0.91), 0.91 (0.88-0.94) and 0.92 (0.89-0.95) respectively (all p < 0.01). The combination of sirtuin-1and anti-MCV gave the highest Youden index of 0.79, whilst Cox regression showed sirtuin-1 and rheumatoid factor were the strongest independent predictors of RA.Conclusions: Serum sirtuin-1 is increased in RA, and may have a place is the diagnosis of this disease when combined with other markers.
34718869 Temperature might increase the hospital admission risk for rheumatoid arthritis patients i 2022 Jan Temperature has been studied in relation to many health outcomes. However, few studies have explored its effect on the risk of hospital admission for rheumatoid arthritis (RA). A distributed lag non-linear model (DLNM) was used to analyze associations between mean temperature, diurnal temperature range (DTR), temperature change between neighboring days (TCN), and daily admissions for RA from 2015 to 2019 in Anqing, China. Subgroup analyses based on age, gender, rheumatoid factors, and admission route were performed. In total, 1456 patients with RA were hospitalized. Regarding the cumulative-lag effects of extreme cold temperature (5th percentile = 3℃), the risks of admissions for RA were increased and highest at lag 0-11 (RR = 2.68, 95% CI: 1.23-5.86). Exposing to low (5th percentile = 1.9℃) and high (95th percentile = 14.2℃) DTRs both had increased risks of RA admission, with highest RRs of 1.40 (95% CI: 1.03-1.91) and 1.24 (95% CI: 1.0-1.53) at lag 0 day, respectively. As for TCN, the marginal risk of admission in RA patients was found when exposed to high TCN (95th percentile = 2.9℃) with the largest single-day effect at lag 10 (RR = 1.11, 95% CI: 1.01-1.23). In subgroup analyses, females were more susceptible to extreme cold temperature, low and high DTRs, and high TCN. In regard to extreme cold temperature, significant risk of hospital admission in females only appeared at lag 2 (RR = 1.48, 95% CI: 1.02-2.15) and lag 0-2 (RR = 2.35, 95% CI: 1.11-4.95). It is clear that RA patients exposed to changing temperature may increase risks of admission.
33461591 Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum 2021 Jan 18 BACKGROUND: To evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles. METHODS: Twelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2. RESULTS: Nine of the women with RA experienced a flare postpartum (RA(Flare)), while three had low disease activity or were in remission (RA(NoFlare)) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RA(Flare) and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RA(Flare) women, and not among the RA(NoFlare) women. Some of these genes were among those whose "normal" expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RA(Flare) compared to both healthy and RA(NoFlare) women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RA(Flare) women. CONCLUSIONS: The large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.
32789440 Influence of proton pump inhibitor or rebamipide use on gut microbiota of rheumatoid arthr 2021 Feb 1 OBJECTIVE: Patients with RA commonly use gastrointestinal (GI) protective drugs for treatment and prevention of drug-associated GI injuries. However, how these drugs affect the gut microbiota in RA patients remains unknown. The objective of this study was to examine the gut microbiota of RA patients according to use of GI protective drugs such as proton pump inhibitors (PPIs), histamine 2-receptor antagonists and rebamipide. METHODS: Faecal samples were obtained from 15 healthy controls and 32 RA patients who were receiving PPI, histamine 2-receptor antagonist or rebamipide. Bacterial DNA was extracted from the faecal samples and 16S rRNA sequencing was performed. Microbial composition and function were analysed using Quantitative Insights Into Microbial Ecology and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. RESULTS: RA patients exhibited reduced diversity and altered composition of the gut microbiota compared with healthy controls. The gut microbiota of RA patients receiving acid-suppressing drugs, particularly PPIs, was distinct from that of RA patients receiving rebamipide (PPI vs rebamipide, P = 0.005). Streptococcus was enriched in RA patients receiving PPI, while Clostridium bolteae was enriched in RA patients receiving rebamipide. The gut microbiota of PPI users was abundant with microbial functional pathway involved in the production of virulence factors. This featured microbial function was positively correlated with relative abundance of Streptococcus, the differentially abundant taxa of PPI users. CONCLUSION: The gut microbiota of RA patients receiving PPIs was distinguishable from that of those receiving rebamipide. The enriched virulent function in the gut microbiota of PPI users suggests that inappropriate PPI use may be harmful in RA patients.
35063223 Validity of bioimpedance for assessment of fat-free mass in women with Rheumatoid Arthriti 2022 Feb BACKGROUND & AIMS: The aim was to assess the validity of bioimpedance in the assessment of fat free mass (FFM) among women and to study if the validity differs between women with and without Rheumatoid Arthritis (RA). METHODS: 38 women with RA and 24 non-rheumatic controls were included. FFM was measured in the non-fasting state using DXA (Lunar Prodigy), multi-frequency bioelectrical impedance analysis (BIA) (MF-BIA [Tanita MC-180 MA]), single-frequency BIA (SF-BIA) and bioelectrical impedance spectroscopy (BIS) (both Impedimed SFB7). BIS raw data were also used to calculate FFM from equations by Matthie, Jaffrin and Moissl. Results were compared using correlation, Bland Altman analysis, Mann Whitney U test and Wilcoxon Signed Ranks Test. RESULTS: Women with RA had different body water distribution compared to women without RA (p < 0.05). Median bias in FFM assessed by bioimpedance was 0.62-7.87 kg with wide limits of agreement for all methods. Median FFM differed significantly from DXA by all bioimpedance methods except for BIS by Jaffrin. Women with RA had significantly smaller biases compared to non-rheumatic controls using BIS equations by Matthie (p = 0.012) and Moissl (p = 0.025). Correlations between FFM measured by DXA and bioimpedance (r = 0.73-0.85, all p < 0.001) did not differ between groups. The sensitivity of bioimpedance to detect low fat free mass index (FFMI) was 0-47%. CONCLUSION: The results of this study show that bioimpedance has similar validity in women with RA compared to non-rheumatic controls, despite differences in body water distribution. Agreement with DXA improved when applying specific equations, but the clinical utility of bioimpedance is questionable as all methods failed to identify low FFMI with acceptable precision. TRIAL REGISTER: Clinicaltrials.org, NCT04247009.