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ID PMID Title PublicationDate abstract
34767108 Machine learning to identify immune-related biomarkers of rheumatoid arthritis based on WG 2022 Apr OBJECTIVES: This study was designed to identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and to explore the potential pathological relevance of immune cell infiltration in this disease. METHODS: Three previously published datasets containing gene expression data from 35 RA patients and 29 controls (GSE55235, GSE55457, and GSE12021) were downloaded from the GEO database, after which a weighted correlation network analysis (WGCNA) approach was utilized to clarify differentially abundant genes. Candidate biomarkers of RA were then identified via the use of a LASSO regression model and support vector machine recursive feature elimination (SVM-RFE) analyses. Data were validated based upon the area under the receiver operating characteristic curve (AUC) values, with hub genes being identified as those with an AUC > 85% and a P value < 0.05. Lastly, the CIBERSORT algorithm was used to assess immune cell infiltration of RA tissues, and correlations between immune cell infiltration and disease-related diagnostic biomarkers were assessed. RESULTS: The green-yellow module containing 87 genes was found to be highly correlated with RA positivity. FADD, CXCL2, and CXCL8 were identified as potential RA diagnostic biomarkers (AUC > 0.85), and these results were validated using the GSE77298 dataset. Immune cell infiltration analyses revealed the expression of hub genes to be correlated with mast cells, monocytes, activated NK cells, CD8 T cells, resting dendritic cells, and plasma cells. CONCLUSION: These data indicate that FADD, CXCL2, and CXCL8 are valuable diagnostic biomarkers of RA, offering new insight that can guide future studies of RA incidence and progression.
33738615 Effects of laser acupuncture tele-therapy for rheumatoid arthritis elderly patients. 2022 Feb Rheumatoid arthritis (RA) is a progressive common autoimmune disorder and is one of the most functional limiting diseases in elderly. Until recently, its treatment is mainly based on physical locations and meetings while being face to face. However, laser acupuncture tele-therapy approaches can significantly provide the patient with safety during the COVID-19 pandemic as well as changing the disorder's prognosis. Sixty patients were assigned randomly into 2 groups with 1:1 ratio. Patients in group A are treated remotely by laser acupuncture in addition to methotrexate and a tele-rehabilitation program in the form of aerobic exercise training. Patients in group B are treated by methotrexate and a tele-rehabilitation program in the form of aerobic exercise. There was a statistically significant difference in health assessment questionnaire (HAQ) pre- and post-treatment in group A (p < 0.05). The C-reactive protein (CRP) and interleukin-6 (IL-6) inflammatory markers as well as the malondialdehyde (MDA) oxidative marker showed a significant reduction pre- and post-treatment in group A (p < 0.05). Additionally, there was a significant increase in the adenosine tri-phosphate (ATP) antioxidant marker pre- and post-treatment in group A (p < 0.05). The comparison between groups A and B showed a statistically significant post-treatment difference in RAQoL, CRP, IL-6, ATP, and MDA in group A than group B. Considering the significant improvement that was found in the laser acupuncture group, it can be concluded that the use of laser acupuncture as adjunctive was effective in the treatment of elderly patients with RA. ClinicalTrials.gov Identifier: NCT04758689.
33276135 Response to interleukin-6 receptor antagonists in patients with rheumatoid arthritis is in 2021 Jan OBJECTIVE: To investigate whether early response to tocilizumab (TCZ) and sarilumab (SAR) therapy in patients with active rheumatoid arthritis (RA) is influenced by previous use of biologic agents. METHODS: We performed a systematic literature review and a meta-analysis of original studies that analyzed the effectiveness of TCZ or SRL in subgroups of RA patients, including biologic-naïve patients versus those with inadequate response to at least one biologic DMARD (bDMARD), and patients with failure to 1 versus≥2 bDMARDs. RESULTS: The study selection process finally included 17 articles corresponding to 14 studies, including 7 randomized controlled trials (RCTs). Although the existing literature that compared the response in biologic-naïve patients versus those with inadequate response to at least one bDMARD showed conflicting results, meta-analysis of 6 published studies revealed a significantly higher likelihood of remission (RR=1.3; 95% CI: 1.2-1.5) and low activity disease (RR=1.3; 95% CI: 1.2-1.4) in the biologic-naïve group at week 24. However, differences between groups were not clinically meaningful in all studies and not always maintained after 6 to 12months of treatment. In addition, data from RCT RADIATE and TARGET suggest that the response to IL-6 pathway inhibitors seems to be similar, regardless of the number of tumor necrosis factor inhibitors (TNFis) previously tested. CONCLUSION: Disease activity was more rapidly reduced in the early stages of treatment in biologic-naïve patients. However, near similar efficacy can be expected in patients who experienced a failure of at least one bDMARD (mainly TNFis) beyond the first 6 to 12months of treatment, suggesting that the response occurs independently of the number of prior TNFis.
34972837 Biased TCR gene usage in citrullinated Tenascin C specific T-cells in rheumatoid arthritis 2021 Dec 31 We aimed to search for common features in the autoreactive T cell receptor (TCR) repertoire in patients with rheumatoid arthritis (RA), focusing on the newly identified candidate antigen citrullinated Tenascin C (cit-TNC). Mononuclear cells from peripheral blood or synovial fluid of eight RA-patients positive for the RA-associated HLA-DRB1*04:01 allele were in-vitro cultured with recently identified citrullinated peptides from Tenascin C. Antigen-specific T cells were isolated using peptide-HLA tetramer staining and subsequently single-cell sequenced for paired alpha/beta TCR analyses by bioinformatic tools. TCRs were re-expressed for further studies of antigen-specificity and T cell responses. Autoreactive T cell lines could be grown out from both peripheral blood and synovial fluid. We demonstrate the feasibility of retrieving true autoreactive TCR sequences by validating antigen-specificity in T cell lines with re-expressed TCRs. One of the Tenascin C peptides, cit-TNC22, gave the most robust T cell responses including biased TCR gene usage patterns. The shared TCR-beta chain signature among the cit-TNC22-specific TCRs was evident in blood and synovial fluid of different patients. The identification of common elements in the autoreactive TCR repertoire gives promise to the possibility of both immune monitoring of the autoimmune components in RA and of future antigen- or TCR-targeted specific intervention in subsets of patients.
34982446 Pain as a mediator in the temperament-alexithymia relationship in individuals suffering fr 2021 Dec OBJECTIVE: The study aims to establish a relationship between temperament traits, symptoms of alexithymia, and pain intensity in rheumatoid arthritis. Despite the significant progress seen in the area of RA treatment, pain, often life-long, remains the predominant symptom. This constant pain and progressing disability, as well as dependence upon other people cause RA patients to experience psychological stress that can be modified by individual patient traits. Recently, several authors have underlined the need to relate personality and temperament constructs to neurobiological processes that may underlie individual differences. It seems then that patient characteristics may play a significant role in the course of the disease. PATIENTS AND METHODS: The study was performed on a group of patients (N=317) with rheumatoid arthritis diagnosed according to the current criteria of the American-European Consensus of 2010. All patients expressed voluntary consent to participate, and the study protocol was approved by the Local Ethics Committee. This was a survey-based study. It involved the application of the adult version of the Buss and Plomin EAS Temperament Questionnaire (EAS-D), which tests 3 main temperament domains: sociability, activity, and emotionality. The pain was measured on the Visual Analogue Scale (VAS). VAS is used to measure pain intensity. The level of alexithymia was tested using the Toronto Alexithymia Scale-20. The scale consists of 20 statements and includes 3 subscales that measure difficulty in describing feelings/emotions, difficulty in identifying feelings/emotions, and operational externally oriented thinking. RESULTS: The analysis revealed that alexithymia is positively correlated only with one dimension of temperament, i.e., emotionality, and with pain intensity. Moreover, high emotionality was positively correlated with pain. A simple mediation analysis revealed that pain intensity functioned as a mediator in the emotionality-alexithymia relationship. CONCLUSIONS: The observed correlations indicate that RA patients with a high level of emotionality exhibit high alexithymia as they perceive pain related to the disease symptoms more intensely. The observed mediation is partial, meaning that there are also other mediating factors in this relationship.
34373933 Sequences of biological treatments for patients with moderate-to-severe rheumatoid arthrit 2022 Jan BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) are recommended to be added in sequentially in the treatment of moderate-to-severe rheumatoid arthritis (RA). All these drugs, however, are substantially more expensive than conventional synthetic DMARDs throughout the world, including in China. The objective of this study is to evaluate the cost-effectiveness of treatment sequences of bDMARDs for patients with moderate-to-severe rheumatoid arthritis from the Chinese healthcare system perspective. METHODS: An individual patient simulation model was used to track the course of patients from first treatment through switches to further lines in a sequence. The comparator treatment sequence commenced with methotrexate, followed by non-biologic therapy. The intervention sequences were assumed to be the combinations of bDMARDs available, followed by non-biologic therapy. Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated. Univariable and probabilistic sensitivity analyses and scenario analyses were performed to evaluate the model uncertainty. RESULTS: Compared with the comparator treatment sequence, bDMARDs sequences were associated with more life years, QALYs, and cost. These produced ICERs ranged from $27,441.36/QALY to $40,149.2/QALY, above the willingness-to-pay threshold of $10,378 per QALY. The uncertainty analyses and the scenario analyses confirmed the result of the base case analysis. CONCLUSIONS: From the perspective of the Chinese healthcare system, bDMARDs sequences are estimated not to be cost-effective compared with conventional synthetic disease-modifying antirheumatic drug strategy for patients with moderate-to-severe RA at a WTP threshold of $10,378 per QALY. Price reductions are warranted to make bDMARDs cost-effective and affordable.
33689803 Neutrophil Extracellular Traps in Inflammatory Bowel Disease: Pathogenic Mechanisms and Cl 2021 The Inflammatory Bowel Diseases (IBD), Ulcerative Colitis (UC) and Crohn's Disease (CD) are characterised by chronic non-resolving gut mucosal inflammation involving innate and adaptive immune responses. Neutrophils, usually regarded as first responders in inflammation, are a key presence in the gut mucosal inflammatory milieu in IBD. Here, we review the role of neutrophil extracellular trap (NET) formation as a potential effector disease mechanism. NETs are extracellular webs of chromatin, microbicidal proteins and oxidative enzymes that are released by neutrophils to contain pathogens. NETs contribute to the pathogenesis of several immune-mediated diseases such as systemic lupus erythematosus and rheumatoid arthritis; and recently, as a major tissue damaging process involved in the host response to severe acute respiratory syndrome coronavirus 2 infection. NETs are pertinent as a defence mechanism at the gut mucosal interphase exposed to high levels of bacteria, viruses and fungi. On the other hand, NETs can also potentiate and perpetuate gut inflammation. In this review, we discuss the broad protective vs. pathogenic roles of NETs, explanatory factors that could lead to an increase in NET formation in IBD and how NETs may contribute to gut inflammation and IBD-related complications. Finally, we summarise therapeutic opportunities to target NETs in IBD.
34704882 Bioactive compounds and therapeutic role of Brassica oleracea L. seeds in rheumatoid arthr 2021 Dec CONTEXT: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and systematic polyarthritis. OBJECTIVE: The present study aimed to isolate and identify the phenolic constituents in Brassica oleracea L. (Brassicaceae) seeds methanolic extract and evaluates its effect against rheumatoid arthritis in rats referring to the new therapy; interleukin-1 receptor antagonist (IL-1RA). MATERIALS AND METHODS: The GC/MS profiling of the plant was determined. Arthritis induction was done using complete Freund's adjuvant. Arthritis severity was assessed by percentage of edema and arthritis index. IL-1 receptor type I gene expression, interleukin-1β (IL-1β), oxidative stress markers, protein content, inflammatory mediators, prostaglandin-E2 (PGE2), genetic abnormalities and the histopathological features of ankle joint were evaluated. RESULTS: For the first time twelve phenolic compounds had been isolated from the seeds extract. Treatment with extract and IL-1RA improved the tested parameters by variable degrees. CONCLUSIONS: RA is an irreversible disease, where its severity increases with the time of induction. Brassica oleracea L. seeds extract is considered as a promising anti-arthritis agent. IL-1 RA may be considered as an unusual therapeutic agent for RA disease. More studies are needed to consider the seeds extract as a nutraceutical agent and to recommend IL-1RA as a new RA drug.
34582480 Platelet mitochondrial respiration and coenzyme Q10 could be used as new diagnostic strate 2021 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimunne disorder affecting both small and large synovial joints, leading to their destruction. Platelet biomarkers are involved in inflammation in RA patients. Increased circulating platelet counts in RA patients may contribute to platelet hyperactivity and thrombosis. In this pilot study we evaluated platelet mitochondrial bioenergy function, CoQ10 levels and oxidative stress in RA patients. METHODS: Twenty-one RA patients and 19 healthy volunteers participated in the study. High resolution respirometry (HRR) was used for analysis of platelet mitochondrial bioenergetics. CoQ10 was determined by HPLC method; TBARS were detected spectrophotometrically. RESULTS: Slight dysfunction in platelet mitochondrial respiration and reduced platelet CoQ10 levels were observed in RA patients compared with normal controls. CONCLUSIONS: The observed decrease in platelet CoQ10 levels may lead to platelet mitochondrial dysfunction in RA diseases. Determination of platelet mitochondrial function and platelet CoQ10 levels could be used as new diagnostic strategies for mitochondrial bioenergetics in rheumatoid diseases.
34659230 Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease v 2021 Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The adipokine apelin (APLN) plays critical roles in several cellular functions, including angiogenesis. We report that APLN treatment of RA synovial fibroblasts (RASFs) increased angiopoietin-1 (Ang1) expression. Ang1 antibody abolished endothelial progenitor cell (EPC) tube formation and migration in conditioned medium from APLN-treated RASFs. We also found significantly higher levels of APLN and Ang1 expression in synovial fluid from RA patients compared with those with osteoarthritis. APLN facilitated Ang1-dependent EPC angiogenesis by inhibiting miR-525-5p synthesis via phospholipase C gamma (PLCγ) and protein kinase C alpha (PKCα) signaling. Importantly, infection with APLN shRNA mitigated EPC angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with collagen-induced arthritis. APLN is therefore a novel therapeutic target for RA.
34147123 Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid 2021 Jun 19 BACKGROUND: A substantial proportion of rheumatoid arthritis (RA) patients discontinues treatment with tumour necrosis factor inhibitors (TNFi) due to inefficacy or intolerance. After the failure of treatment with a TNFi, treatment can be switched to another TNFi or a bDMARD with a different mode of action (non-TNFi). Measurement of serum drug concentrations and/or anti-drug antibodies (therapeutic drug monitoring (TDM)) may help to inform the choice for the next step. However, the clinical utility of TDM to guide switching has not been investigated in a randomised test-treatment study. METHODS: ADDORA-switch is a 24-week, multi-centre, triple-blinded, superiority test-treatment randomised controlled trial. A total of 84 RA patients failing adalimumab treatment (treatment failure defined as DAS28-CRP > 2.9) will be randomised in a 1:1 ratio to a switching strategy to either TNFi or non-TNFi based on adalimumab serum trough level (intervention group) or random allocation (control group). The primary outcome is the between-group difference in mean time-weighted DAS28 over 24 weeks. DISCUSSION: The trial design differs in many aspects from previously published and ongoing TDM studies and is considered the first blinded test-treatment trial using TDM in RA. Several choices in the design of this trial are described, and overarching principles regarding test-treatment trials and clinical utility of TDM are discussed in further detail. TRIAL REGISTRATION: Dutch Trial Register NL8210 . Registered on 3 December 2019 (CMO NL69841.091.19).
34164737 Can treating rheumatoid arthritis with disease-modifying anti-rheumatic drugs at the windo 2021 Nov OBJECTIVE: The aim of this retrospective study is to compare the results of starting rheumatoid arthritis (RA) treatment with tight control strategy in the window of opportunity and later phases of the disease in real-world clinical practice. METHODS: In this cohort, 609 RA patients were divided into three groups: (i) very early treatment (VET): ≤ 3 months; (ii) early treatment (ET): 3-12 months; and (iii) late treatment (LT) > 12 months after the onset of the disease. Four levels of remission were defined: (i) sustained remission on treatment, (ii) sustained glucocorticoids free remission, (iii) sustained disease-modifying anti-rheumatic drugs (DMARDs) free remission, and (iv) long-term remission. Outcome was assessed based on the number of patients in sustained or long-term remission and patients with poor joint outcome and systemic involvement. RESULTS: There were no significant differences in the remission rate between the groups. Time to sustained remission in VET group was shorter than ET and LT groups. There were no significant differences in the rate and duration of prednisolone discontinuation in the studied groups. DMARDs were discontinued in VET, ET, and LT groups in 8.7%, 10.2%, and 7% of the patients, respectively. Poor joint outcome occurred in 33.2%, 50.5%, and 59.4% of the patients in the VET, ET, and LT groups, respectively. Remission induction in the first year of the treatment was associated with long-term remission in the VET, ET, and LT groups. CONCLUSIONS: Medications free remission in RA is rare, and although treatment with DMARDs within 3 months of the onset of the disease can prevent joint damage, it cannot lead to long-term remission and discontinuation of medications. KEY POINTS: • Medications free remission in rheumatoid arthritis is rare. • Treatment with DMARDs within 3 months of the onset of the disease can prevent joint damage, but it cannot lead to long-term remission and discontinuation of medications.
34404786 Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive an 2021 Aug 17 The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45(+) hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.
33713557 Diagnostic value of anti-citrullinated α-enolase peptide 1 antibody in patients with rheu 2021 May AIM: To evaluate the diagnostic value of anti-citrullinated α-enolase peptide 1 (anti-CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic review and meta-analysis. METHODS: The PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases were searched for relevant studies published until September 23, 2020. A bivariate mixed-effects model was used to calculate the diagnostic indices from primary data of eligible studies. We performed meta-regression and subgroup analysis to explore the sources of heterogeneity. RESULTS: Twenty-four articles, with a total of 17 380 patients with RA and 7505 control participants, met the criteria for inclusion in the meta-analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios for the anti-CEP 1 antibody were 44% (95% CI: 38%-51%), 97% (95% CI: 96%-98%), and 14.81 (95% CI: 10.66-20.57) and 0.57 (95% CI: 0.52-0.64), respectively. The pooled positive and negative predictive values were 0.96 (95% CI: 0.95-0.97) and 0.53 (95% CI: 0.43-0.63), respectively. The area under the summary receiver operating characteristic curve was 0.86. Meta-regression indicated that the anti-CEP 1 antibody detection method may be a source of heterogeneity. The subgroup analysis of the group in which the anti-CEP 1 antibody was detected by using a commercial enzyme-linked immunosorbent assay (ELISA) kit had a sensitivity of 59% (95% CI: 50%-68%) and a specificity of 93% (95% CI: 85%-97%). CONCLUSIONS: The anti-CEP 1 antibody had moderate RA diagnostic value with relatively low sensitivity and high specificity. An ELISA may increase the RA diagnostic sensitivity.
34968861 A deep-learning framework for metacarpal-head cartilage-thickness estimation in ultrasound 2022 Feb OBJECTIVE: Rheumatoid arthritis (RA) is a chronic disease characterized by erosive symmetrical polyarthritis. Bone and cartilage are the main joint targets of this disease. Cartilage damage is one of the most relevant determinants of physical disability in RA patients. Cartilage damage is nowadays assessed by clinicians, which manually measure cartilage thickness in ultrasound (US) imaging. This poses issues relevant to intra-and inter-observer variability. Relying on the acquisition of metacarpal-head US images from 38 subjects, this work addresses the problem of automatic cartilage-thickness measurement by designing a new deep-learning (DL) framework. METHODS: The framework consists of a Convolutional Neural Network (CNN), responsible for regressing cartilage-interface distance fields, followed by a post-processing step to delineate the two cartilage interfaces from the predicted distance fields and compute the cartilage thickness. RESULTS: Our framework achieved encouraging results with a mean absolute difference (ADF) of 0.032 (±0.026) mm against manual thickness annotation by an expert clinician. When evaluating the intra-observer variability, we obtained an ADF = 0.036 (±0.028) mm. CONCLUSION: The proposed framework achieved an ADF against manual annotation that was comparable to the intra-observer variability, proving the potential of DL in the field. SIGNIFICANCE: This work is the first to address the problem of automatic cartilage-thickness estimation in US rheumatological images with DL, paving the way for future research in the field. From a clinical perspective, the proposed framework proved to be a valuable tool to support the clinical routine increasing the reproducibility of cartilage thickness measurements.
34407926 EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. 2022 Jan OBJECTIVE: To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. RESULTS: Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). CONCLUSIONS: These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research.
33921207 Association between Malnutrition and Quality of Life in Elderly Patients with Rheumatoid A 2021 Apr 12 Rheumatoid arthritis (RA) is a progressive articular disease. In addition to damaging the joints, it may cause multiple organ complications, and considerably impair the patient's functioning. Elderly patients with RA report pain, fatigue, mood disorders, sleep disorders and insomnia, accompanied by weakness, poor appetite, and weight loss. All these factors combined have an adverse effect on the patient's perceived quality of life (QoL). Due to the chronic nature of RA and the high risk of malnutrition in this patient group, the present study investigated QoL, activities of daily living, and frailty syndrome severity in relation to MNA (Mini Nutritional Assessment) questionnaire scores among elderly RA patients. The study included 98 patients (aged over 60) diagnosed with RA per the ARA (American Rheumatism Association) criteria. The following standardized instruments were used: WHOQoL-BREF for QoL, the Edmonton Frail Scale for frailty syndrome severity, MNA for nutritional status assessment, and MMSE (Mini-Mental State Examination) to assess any cognitive impairment. Medical data were obtained from hospital records. Patients with a different nutritional status differed significantly in terms of limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL). Higher levels of malnutrition were associated with greater limitations in activity. An adverse impact of lower body weight on cognitive function was also observed (dementia was identified in 33.33% of malnourished patients vs. 1.79% in patients with a normal body weight). Likewise, frailty was more common in malnourished patients (mild frailty syndrome in 33.3%, moderate in 16.67%, and severe in 16.67%). Malnourished patients had significantly lower QoL scores in all WHOQoL-BREF questionnaire domains than those with a normal body weight, and multiple-factor analysis for the impact of selected variables on QoL in each domain demonstrated that frailty was a significant independent determinant of poorer QoL in all domains: perceived quality of life (β = -0.069), perceived health (β = -0.172), physical domain (β = -0.425), psychological domain (β = -0.432), social domain (β = -0.415), environmental domain (β = -0.317). Malnutrition was a significant independent determinant of QoL in the "perceived health" domain (β = -0.08). In addition, regression analysis demonstrated the positive impact of male sex on QoL scores in the psychological (β = 1.414) and environmental domains (β = 1.123). Malnourished patients have a lower QoL than those with a normal body weight. Malnutrition adversely affects daily functioning, cognitive function, and the severity of frailty syndrome. Frailty syndrome is a significant independent determinant of poorer QoL in all WHOQoL BREF domains.
34189672 Serum anti-citrullinated protein antibodies and rheumatoid factor increase the risk of rhe 2021 Nov BACKGROUND: This meta-analysis aims to determine the association between antibodies including anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) and risk of rheumatoid arthritis-related interstitial lung disease (RA-ILD). METHODS: PubMed, Embase, and Cochrane were searched up to September 13, 2020, for studies investigating the risk of RA-ILD in ACPA-positive patients. The statistical meta-analysis and sensitivity analysis were performed using the Review Manager 5.4 and Stata16.0 software, respectively. RESULTS: Total 1 double-blind randomized controlled study and 16 observational studies, including 992 RA-ILD patients and 2223 RA-non ILD patients, met the inclusion criteria of the meta-analysis. Compared with ACPA-negative patients, positive serum ACPA increased the risk of RA-ILD (OR = 2.51; 95% CI: 1.35-4.68; P = 0.004) and serum ACPA titer was significantly correlated with risk of RA-ILD (SMD = 0.39; 95% CI: 0.17-0.62; P = 0.0006). In a region-based subgroup analysis, ACPA titer in Asian, European, and African populations was significantly related to the risk of RA-ILD, while there was no significant correlation in the Americans (SMD =  - 0.03; 95% CI: - 0.89-0.83; P = 0.95), especially in the USA (SMD = 0.37; 95% CI: - 0.26-0.99; P = 0.25). In addition, serum positive RF increased the risk of RA-ILD (OR = 2.85; 95% CI: 2.19-3.71; P < 0.00001) and serum RF titer was significantly correlated with the risk of RA-ILD (SMD = 0.35; 95% CI: 0.23-0.46; P < 0.00001). However, for the analysis of RF dichotomous data, the funnel shape was asymmetric and the p value of egger test was less than 0.05, which indicated potential publication bias. CONCLUSIONS: ACPA and RF positive patients have greater risk of RA-ILD, and RA patients positive for ACPA should be paid more attention. KEY POINTS: • Autoantibodies ACPA and RF increase the risk of RA-ILD. • Regions may be related to RA-ILD.
34735922 MYD88, IRAK3 and Rheumatoid Arthritis pathogenesis: Analysis of differential gene expressi 2021 Nov Rheumatoid arthritis (RA) is a well-known chronic inflammatory disorder. Two molecular players act in the inflammation balance of the disease: MyD88 (Myeloid differentiation primary response 88) is related to TLR (Toll-like receptors) response and promotes the formation of myddosome complex resulting in increased inflammation; IRAK3 (Interleukin-1 receptor associated kinase 3) acts suppressing the myddosome complex thus decreasing inflammation. In this scenario, MYD88 and IRAK3 gene expression profile in RA patients and its correlation with clinical features is still partially known. So, we evaluated the MYD88 and IRAK3 gene expressions in CD14 + monocytes from RA patients and healthy controls and its relation with patients' clinical features and cytokine plasma levels. CD14 + monocytes were isolated using positive selection by magnetic cell separation. The MYD88 and IRAK3 gene expressions were measured through real time relative quantitative PCR with specific primers; relative quantification was normalized to ACTB, GAPDH, 18S and RPLP0 reference genes. Cytokine levels were analyzed by CBA (cytokine beads assays). CD14 + monocytes from RA patients showed lower IRAK3 expression level compared to controls although with a borderline statistical significance (Fold change (FC) = -1.63; p = 0.054). Furthermore, RA patients with high disease activity had lower levels of IRAK3 when compared to patients with low/moderate activity measured by the CDAI index (FC = -1.78; p = 0.030). No significant differences were observed for MYD88 gene expression (FC = 1.20; p = 0.294) between patients and controls analyzed. Additionally, we did not we did not observe correlation between IRAK3 and MYD88 gene expression and TNF-α, IL-6, IL-2 and IL-10 levels. We suggested that IRAK3 gene expression in CD14 + monocytes appears to be relevant to the RA etiology and clinical activity, whereas, in this study, MYD88 does not play a role in RA onset and development.
34625148 Musculoskeletal disorders due to chikungunya virus: A real experience in a rheumatology de 2021 Oct BACKGROUND: Chikungunya (CHIKV), is an endemic RNA virus in some regions of Asia and Africa. In Colombia in 2014, its spread started explosively and quickly. The presentation of CHIKV is a febrile condition, with musculoskeletal symptoms, which can progress to erosive arthropathy and polyarticular deformity. The purpose of this study is to evaluate symptomatic and serological behaviour in patients suffering from CHIKV infection in Neiva, Huila who attend the Rheumatology clinic, and to describe the comorbidities associated with the chronic phase of the disease. METHODS: An observational, longitudinal and retrospective analysis of data collected in 410 patients afflicted with the CHIKV virus, with symptoms lasting more than 3 months, who persisted with musculoskeletal and joint symptoms. The patients were classified according to their commitment in post-viral arthralgias, polyarthritis post viral, Rheumatoid Arthritis (RA) post CHIKV, Spondyloarthritis postCHIKV, and soft tissue rheumatism. The statistical analysis was performed using SPSS software (version 24). A descriptive analysis was carried out to evaluate quantitative variables such as the mean (standard deviation), and categorical variables such as frequency (%). The categorical variables were compared using the Chi-square equation. As a statistical significance, a p less than .05 was considered. RESULTS: Of the 410 patients, 89.23% were women, with polyarticular involvement in 92.26% of the cases. Of the patients, 49.83% had osteoarthritis. At the time of the evaluation in the Rheumatology clinic, 46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination, of which, remarkably, 20.3% met the criteria for rheumatoid arthritis postCHIKV. CONCLUSIONS: The development of musculoskeletal symptoms after CHIKV infection is a very serious public health problem, with persistent complications and long-term morbidity risk in real life. The presence of net postviral arthritis is noteworthy, however the development of postCHIKV rheumatoid arthritis usually requires more advanced pharmacological measures, including, in some cases, transition to biological therapy. The presence of symptoms of venous insufficiency in the lower limbs that developed with CHIKV infection was an incidental finding that requires a more precise study.