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

ID PMID Title PublicationDate abstract
32664175 Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rhe 2020 Jul 10 Cervus and cucumis peptides (Lugua polypeptides, LG) are traditional Chinese medicine, which are active components of polypeptide extracted from Sika deer bone and melon seed, and they contain bone induced polypeptide biological factors. Umbilical cord mesenchymal stem cell, (UC-MSC) have tissue repair multiple effects, anti-inflammatory, and immune regulation function, which become a very promising start in rheumatoid arthritis (RA) treatment. Hence, LG combined UC-MSC can significantly enhance the UC-MSC treatment of rheumatoid arthritis (RA).To explore the clinical curative effect and therapeutic mechanism of LG combined UC-MSC for treating RA.119 patients were divided into control and treatment groups, and both groups were treated with methotrexate tablets, leflunomide, and UC-MSC. But, LG were added to the treatment group. In vitro, the effects of LG on UC-MSC cell secretion of anti-inflammatory factors were also performed.The Health Assessment Questionnaire; the 28 joint disease activity score; C reactive protein; the erythrocyte sedimentation rate; rheumatoid factor; and anti-cyclic citrullinated peptide antibody were significantly reduced in treatment group 1 year after treatment (P < .05). In vitro, compared with the control group, the number of hepatocyte growth factor (HGF), the secretion of prostaglandin E2 (PGE2) and tumor necrosis factor-inducible gene 6 protein (TSG6) increased significantly (P < .05).LG combined UC-MSCs can significantly improve the curative effect of RA patients, while LG may reduce inflammatory cytokines, regulate immunity, improve microcirculation, and are conducive to UC-MSCs migration and the repair of damaged tissue.
33009599 Chronological effects of non-steroidal anti-inflammatory drug therapy on oxidative stress 2021 May INTRODUCTION/OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing pain and inflammation in rheumatoid arthritis and other joint- and muscle-associated diseases. However, the extensive, long-term, and over the counter administration of NSAIDs may cause various side effects in the patients. In the present study, the chronological effect of NSAIDs on oxidative stress and antioxidant status in patients with rheumatoid arthritis was studied. METHODS: The study included 100 female individuals categorized in four major groups: (1) control group consisting of age- and gender-matched healthy individuals, (2) NRA-NSAID individuals taking NSAIDs without any history of RA, (3) RA individuals with a history of RA but not taking NSAIDs, and (4) RA-NSAID individuals with chronic RA and taking NSAIDs for a long period. The sera of the participants were analyzed for the oxidative stress and antioxidant status. RESULTS: The RA-NSAID group showed the significantly highest oxidative stress, in terms of malondialdehyde content and lipid-reducing ability as determined in thiocyanate and hemoglobin-induced linoleic acid systems. However, the free radical scavenging ability of the RA-NSAID group, against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide, and 2,2-azino-bis-tetrazolium sulfate radicals, was found to be lower than those of the other study groups. The regression analysis of the experimental data showed a significant positive relationship between duration of NSAID intake and malondialdehyde production, lipid-reducing ability, and metal chelating ability in the RA-NSAID patients. The free radical scavenging abilities of the RA-NSAID group were negatively correlated with the duration of NSAID intake. CONCLUSIONS: The prolonged use of NSAIDs significantly increased the oxidative stress and decrease the antioxidant potential of both the RA patients and NRA individuals. The study provides awareness to the public particularly the RA patients regarding the risk of oxidative stress-associated abnormalities caused by the frequent and prolonged use of NSAIDs for temporary relief from pain. Key Points • The study presents the effects of long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) on antioxidant status of patients with rheumatoid arthritis. • The continuous administration of NSAIDs has been found to significantly increase the oxidative stress of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The prolonged NSAID therapy also decreased the antioxidant potential of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The study would be a significant and valuable contribution to the literature for the awareness regarding the use of NSAIDs.
32815692 Red puffy hand syndrome mistaken for inflammatory arthritis. 2020 Jun 15 Red puffy hand syndrome is an uncommon clinical manifestation of intravenous drug abuse, which presents with bilateral, painless and non-pitting erythema and edema of the dorsal hands. The pathophysiology is believed to primarily be the result of lymphatic blockage from either direct toxicity of the injected drug, drainage of impurities, or infection complications. A woman in her 40's with remote intravenous drug use presented with over a decade of fixed, painless erythema and swelling of bilateral dorsal hands. Owing to an elevated rheumatoid factor, which would later be attributed to patient's untreated hepatitis C, these findings were mistaken for rheumatoid arthritis and unnecessarily treated with methotrexate and prednisone. Upon proper recognition of her underlying Red puffy hand syndrome, systemic medications were discontinued and appropriate care was initiated with lymphedema decongestion and occupational therapy. Red puffy hand syndrome, albeit rare, is an important manifestation of intravenous drug abuse; its recognition will spare patients from unnecessary systemic treatments.
33274243 The Role of Yersinia enterocolitica O:3 Lipopolysaccharide in Collagen-Induced Arthritis. 2020 Yersinia enterocolitica O:3 is mentioned among the most common arthritogenic pathogens. Bacterial components (including lipopolysaccharide (LPS)) may persist in the joint after eradication of infection. Having an adjuvant activity, LPS may enhance production of anticollagen antibodies, involved in the pathogenesis of rheumatoid arthritis. Furthermore, its ability to activate complement contributes to the inflammation. The aim of this work was to investigate whether Yersinia LPS (coinjected with collagen) is associated with arthritis progression or other pathological effects and to elucidate the mechanism of this association. It was demonstrated that murine mannose-binding lectin C (MBL-C) recognizes the inner core heptoses of the Rd1 chemotype LPS of Yersinia. In addition, the Rd1 LPS activates the MBL-associated serine protease 1 (MASP-1) stronger than the S and Ra chemotype LPS and comparable to Klebsiella pneumoniae O:3 LPS. However, in contrast to the latter, Yersinia Rd1 LPS was associated neither with the adjuvancity nor with the enhancement of pathological changes in animal paws/impairment of motility. On the other hand, it seemed to be more hepatotoxic when compared with the other tested endotoxins, while the enlargement of inguinal lymph nodes and drop in hepatic MBL-C expression (at the mRNA level) were independent of LPS chemotype. Our data did not suggest no greater impact Y. enterocolitica O:3 on the development or severity of arthropathy related to anticollagen antibody-induced arthritis in mice, although its interaction with MBL-C and subsequent complement activation may contribute to some adverse effects.
32807591 Reweighting to address nonparticipation and missing data bias in a longitudinal electronic 2020 Oct PURPOSE: We examined whether weighting techniques could account for longitudinal differences in disease activity by race/ethnicity between research participants and nonparticipants with rheumatoid arthritis (RA). METHODS: We included 377 patients with RA from a public hospital in San Francisco, CA. We estimated the probability of not enrolling in a research study by constructing weights using inverse probability weighting. Disease activity over time by race/ethnicity was analyzed across the entire patient population and among research participants only using multivariable mixed-effects models. RESULTS: There were no differences in RA disease activity scores between research participants and nonparticipants at baseline; however, longitudinal differences in disease activity between research participants and nonparticipants were found by race/ethnicity. Weighting research participants in accordance with sociodemographic and clinical characteristics of the nonparticipant population did not result in any meaningful changes in disease activity by race/ethnicity over time. CONCLUSIONS: In our study of patients with RA, inverse probability weighting using select sociodemographic and clinical variables was not sufficient to account for longitudinal disease activity differences by race/ethnicity between research participants and nonparticipants.
31758423 Iguratimod dose dependently inhibits the expression of citrullinated proteins and peptidyl 2020 Mar INTRODUCTION: Anti-citrullinated protein antibodies (ACPAs) play an important role in rheumatoid arthritis (RA). Citrullinated proteins (CPs), which are produced by post-translational modification via peptidylarginine deiminase (PAD), are the target antigen of ACPAs and promote the generation thereof. Herein, we investigated whether iguratimod (IGU) affects the generation of CPs via PAD. METHODS: Neutrophils and peripheral blood mononuclear cells (PBMCs) were isolated from three patients diagnosed with RA and treated with various concentrations of IGU, methotrexate (MTX), or dexamethasone (DXM) or without any drugs as a control for 8 h. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in culture supernatants were tested by ELISA. CPs were measured by western blot, and the expression of PAD2 and PAD4 in cells was detected by qRT-PCR and western blot. RESULTS: PAD2 and PAD4 expressions in neutrophils but not in PBMCs were decreased by IGU at both the protein and mRNA levels (P < 0.05). CP expression in neutrophils but not in PBMCs was also inhibited by IGU. The inhibitory effect of IGU was dose-dependent. IGU, MTX, and DXM dose dependently decreased the secretion of TNF-α, IL-1β, IL-6, and IL-8 in neutrophils and PBMCs (P < 0.05); the inhibitory effect of IGU was not significantly different from that of MTX and DXM. CONCLUSIONS: IGU inhibited the expression of CPs by downregulating PADs in neutrophils from RA patients, and the effect was comparable to that of MTX and DXM at appropriate concentrations. These findings may provide guidance for more appropriate treatment of RA.Key Points• Iguratimod inhibited citrullinated protein expression in neutrophils from rheumatoid arthritis patients similarly to methotrexate and dexamethasone at appropriate concentrations.• The inhibitory effect was mediated by downregulation of peptidylarginine deiminases, providing insight into the mechanism of iguratimod as a treatment for rheumatoid arthritis.• This study may guide rheumatoid arthritis treatment and facilitate identification of other therapeutic targets.
32722921 Golimumab improves patient-reported outcomes in daily practice of inflammatory rheumatic d 2020 Aug Aim: To analyze the quality of life (QoL), work productivity and activity impairment (WPAI) and healthcare resource utilization (HCRU) in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients receiving golimumab under routine clinical settings in Germany. Materials & methods: Prospective observational study, GO-ART, analyzed changes in WPAI, QoL and HCRU during 24 months of golimumab therapy. Results: Seven hundred and forty-eight patients (RA = 250, PsA = 249 and AS = 249) were enrolled. Substantial improvements in WPAI scores presenteeism, activity impairment and total work productivity impairment and QoL were observed at month three and were maintained through month 24. Fewer patients had disease-related hospitalizations and consulted physician at month 24 than at the baseline. Conclusion: Golimumab induces sustained improvements in WPAI and QoL and reduces healthcare resource utilization in RA, PsA and AS.
32237325 [Differences in intestinal absorption characteristics of Laportea bulbifera extract in nor 2020 Jan This work aimed to investigate the intestinal absorption characteristics of Laportea bulbifera extract in normal and rheumatoid arthritis model rats. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, kaempferol-3-O-rutinoside, galuteolin, quercetin and isoquercetin in intestinal absorption solution samples were detected by UPLC-MS/MS with 5.0 g·L~(-1) as the absorption concentration. The cumulative absorption(Q) and absorption rate constant(K_a) were calculated, and the absorption characteristics of different components of L. bulbifera in intestinal absorption solution of normal rats and rheumatoid arthritis rats were compared. The results showed that all the eight index components in the extract of L. bulbifera could be absorbed into the intestinal capsule, the cumulative absorption-time curve of each component showed an upward trend without saturation, and the correlation regression coefficient(R~2) was greater than 0.92, which is consistent with the zero-order absorption rate process. It was speculated that the possible absorption mode of each component was passive diffusion. In normal condition, the absorption of ileum was the best(except chlorogenic acid), and in pathological condition, duodenum was the best. The total absorption of 8 components in each intestinal segment of RA rats was better than that of normal rats, which speculated that rheumatoid arthritis may change the specific site of drug absorption. The experimental results showed that rheumatoid arthritis could change the intestinal absorption of the extract of L. bulbifera, and its mechanism needs further study.
32024651 Testing different thresholds for patient global assessment in defining remission for rheum 2020 Apr OBJECTIVES: This study aimed to evaluate different patient global assessment (PGA) cut-offs required in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission definition for their utility in rheumatoid arthritis (RA). METHODS: We used data from six randomised controlled trials in early and established RA. We increased the threshold for the 0-10 score for PGA gradually from 1 to 3 in steps of 0.5 (Boolean1.5 to Boolean3.0) and omitted PGA completely (BooleanX) at 6 and 12 months. Agreement with the index-based (Simplified Disease Activity Index (SDAI)) remission definition was analysed using kappa, recursive partitioning (classification and regression tree (CART)) and receiver operating characteristics. The impact of achieving each definition on functional and radiographic outcomes after 1 year was explored. RESULTS: Data from 1680 patients with early RA and 920 patients with established RA were included. The proportion of patients achieving Boolean remission increased with higher thresholds for PGA from 12.4% to 19.7% in early and 5.9% to 12.3% in established RA at 6 months. Best agreement with SDAI remission occurred at PGA cut-offs of 1.5 and 2.0, while agreement decreased with higher PGA (CART: optimal agreement at PGA≤1.6 cm; sensitivity of PGA≤1.5 95%). Changing PGA thresholds at 6 months did not affect radiographic progression at 12 months (mean ꙙsmTSS for Boolean, 1.5, 2.0, 2.5, 3.0, BooleanX: 0.35±5.4, 0.38±5.14, 0.41±5.1, 0.37±4.9, 0.34±4.9, 0.27±4.7). However, the proportion attaining HAQ≤0.5 was 90.2%, 87.9%, 85.2%, 81.1%, 80.7% and 73.1% for the respective Boolean definitions. CONCLUSION: Increasing the PGA cut-off to 1.5 cm would provide high consistency between Boolean with the index-based remission; the integer cut-off of 2.0 cm performed similarly.
31857078 Expression and methylation levels of suppressor of cytokine signaling 3 in rheumatic arthr 2020 Apr BACKGROUND: In the present study, we aimed to understand the expression and methylation levels of the suppressor of cytokine signaling 3 (SOCS3) in rheumatoid arthritis (RA) synovial fibroblasts. METHOD: The RA model was established using Freund's complete adjuvant, and then the synovial fibroblasts were isolated and cultured. Next, RNA extraction and reverse transcription were performed. The SOCS3 transcription level was detected using qPCR, and SOCS3 protein expression was detected using western blotting (WB). Lastly, methylation-specific PCR (MSP) was performed. RESULTS: The RA model was successfully demonstrated. SOCS3 gene (p < .01) and protein expression levels were significantly increased in the RA rat group compared to in the wild type (WT) group. However, no significant difference was observed in the MSP products between the RA and WT groups. CONCLUSION: The increased expression of the SOCS3 can be correlated with the development of RA.
32150095 A case report of immune-mediated arthritis in a patient with cutaneous melanoma receiving 2020 Mar INTRODUCTION: Immune checkpoint inhibitors (ICIs) represent an important advance in the treatment of melanoma. ICIs may induce autoimmune phenomena caused by concurrent activation of the immune system against normal cells. During the last years, cases of musculoskeletal side effects, especially immune-mediated arthritis (IA), have been increasingly reported. PATIENT CONCERNS: We present a 59-year-old woman, who was treated with pembrolizumab for a relapsed BRAF V600E mutated cutaneous malignant melanoma. The patient presented with right knee arthritis on week 30. DIAGNOSIS: The erythrocyte sedimentation rate and serum C-reactive protein levels were elevated, while rheumatoid factor and anti-cyclic citrullinated peptide antibodies were negative. Imaging confirmed the presence of fluid mainly in the suprapatellar bursa. Synovial fluid analysis revealed an inflammatory effusion, while other etiologies of inflammatory arthritis were excluded. INTERVENTIONS: Arthritis improved with an intra-articular injection of 8 mg dexamethasone. Twelve days later the arthritis relapsed in both knees, and although it was resistant to nonsteroidal anti-inflammatory treatment, it improved with systemic steroids. Tapering of methylprednisolone dose was feasible with the coadministration of leflunomide and subsequently hydroxychloroquine. OUTCOMES: Arthritis resolved and the patient is free of complications and disease activity 20 months after the initiation of the second line systemic treatment. CONCLUSIONS: We present an unusual case of IA associated with pembrolizumab treatment. The originality of the current report is based on the late occurrence, the monoarticular initial distribution, and uncommon location of IA at the knee.
31932747 Immunological adaptations in pregnancy that modulate rheumatoid arthritis disease activity 2020 Feb During pregnancy, the fetus that grows within the maternal uterus is not rejected by the maternal immune system. To enable both tolerance towards the fetus and defence against pathogens, modifications of the maternal immune system occur during gestation. These modifications are able to bring about a natural improvement in disease activity of some autoimmune diseases, such as rheumatoid arthritis (RA). Various mechanisms of the immune system contribute to the phenomenon of pregnancy-related improvement of RA, and the cessation of these immunomodulatory mechanisms after delivery correlates with postpartum disease flare. HLA disparity between mother and fetus, glycosylation of IgG, immunoregulatory pathways, and alterations in innate and adaptive immune cells and their cytokines have important roles in pregnancy and in pregnancy-related amelioration of RA.
32896702 Definition of B cell helper T cells in rheumatoid arthritis and their behavior during trea 2020 Oct BACKGROUND: Immunopathogenesis of rheumatoid arthritis (RA) is not yet clearly defined. Besides known B-cell involvement, RA development and evolution involves CD4(+) T helper cell homeostasis dysregulation. Imbalance between Th17 cells and regulatory T cells have been reported and may contribute to sustained inflammation. Since the last decade, increasing reports focused on a newly described CD4(+) T helper cell subset, called T follicular helper (Tfh) cells, functionally distinct from other subsets due to their own property to provide help to B cells by enhancing their survival and differentiation into long-lasting antibody secreting cells. More recently, another B cell helper subset, named T peripheral helper (Tph) cells, has been specifically described in synovial tissues and blood of RA patients. METHODS: We conducted an exhaustive and careful literature search focusing our interest on T cells specialized on B cell help, Tfh cells and Tph cells, in RA pathogenesis and focused on their modulation during treatments. RESULTS: Tfh cells and in higher proportions Tph cells were described in synovial tissue and liquid of RA patients. In blood of RA patients, despite the use of diverse Tfh cell definitions, a vast majority of reports revealed an increase of circulating Tph and Tfh cell frequency, compared to healthy controls. However, discordant correlations between disease activity score and either effector or activated circulating Tfh cell subsets were highlighted, probably due to heterogeneity of cohort design in term of definition of disease activity, cohort size and use of different treatments. Indeed, frequencies of circulating Tfh and Tph cells are modulated depending on the nature and duration of RA treatment. Interestingly, it has been demonstrated that the proportion of ICOS-expressing blood Tfh cells before abatacept initiation was an independent and significant predictor of DAS28-ESR improvement at week 24. This report may encourage to conduct further investigations based on T-cell subsets as predictive biomarkers of response to biotherapies. CONCLUSION: Mounting evidences hypothesize that circulating Tfh and Tph cells may be involved in RA pathogenesis and response to treatment.
32303781 Inhibition of glycolysis ameliorate arthritis in adjuvant arthritis rats by inhibiting syn 2020 Jun OBJECTIVE: This study aimed to evaluate glycolysis inhibitor which can effectively ameliorate arthritis by inhibiting synoviocyte activation through AMPK/NF-кB pathway in AA rats. METHODS: Adjuvant arthritis (AA) rats were treated with 2-deoxyglucose (2-DG), glycolysis inhibitor. HE staining and radiological Examination were used for histopathology analysis and evaluation of joint destruction. HKII expression was quantified by immunostaining. Proliferation and migration of synoviocytes were assessed by synovicyte scores of joint, CCK8 and transwell assay. Inflammatory factors and levels of AMPK, p65 and IκBα were quantified by ELISA analysis and WB. RESULTS: We observed that HKII expression was positively correlated with synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction, and glycolysis inhibitor reduces the joint swelling degree, alleviates bone destruction, inhibits the proliferation and migration of synoviocyte, and reduces secretory function of synoviocytes in AA rats. In addition, we investigated that glycolysis inhibitor may inhibit activation of the NF-κB signaling pathway by activating the AMPK pathway. CONCLUSION: This study suggests the involvement of energy metabolism in the pathological inflammation process in RA joints. Glycolysis inhibitors might, therefore, provide an opportunity for therapeutic intervention.
33039536 A review on the wide range applications of hyaluronic acid as a promising rejuvenating bio 2020 Dec 15 Hyaluronic acid (HA) is a multifunctional high molecular weight polysaccharide produced by synoviocytes, fibroblasts, and chondrocytes, and is naturally found in many tissues and fluids, and more abundantly in articular cartilage and synovial fluid. Naturally occurring HA is thought to participate in many biological processes, such as regulation of cell adhesion and cell motility, manipulation of cell differentiation and proliferation, and providing mechanical properties to tissues (Girish and Kemparaju, 2007). Due to its excellent physicochemical properties such as high viscosity, elasticity, biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity, HA based formulations have a wide range of applications and serves as a promising rejuvenating biomacromolecule in biomedical applications. In recent decades, HA is currently a popular topic, and has been widely used in bone related diseases for its remarkable efficacy in articular cartilage lubrication, analgesia, anti-inflammation, immunomodulatory, chondroprotection, anti-cancer and etc. Moreover, the safety and tolerability of HA based formulations have also been well-documented for treatment of various types of bone related diseases (Chen et al., 2018). This review gives a deep understanding on the special benefits and provides a mechanism-based rationale for the use of HA in bone related diseases conditions with special reference to osteoarthritis (OA), rheumatoid arthritis (RA), bone metastatic cancers.
32242805 Lower frequency of anti-citrullinated protein antibodies among early arthritis patients wi 2020 Nov OBJECTIVES: To investigate the role of body mass index (BMI) in the phenotypic and genotypic characteristics of early arthritis patients. METHODS: We analysed the clinical and laboratory parameters from the baseline visit of patients (670 patients [78.51% women]) included in the PEARL study. The WHO definition for low weight, normal weight, overweight and obesity (BMI <18.5, 18.5-25, 25-30 or ≥30 kg/m2, respectively) was applied. Anticitrullinated protein antibodies (ACPA) were studied by ELISA and HLA-DRB1* were genotyped by sequence speci c oligonucleotide probes. The relationship between BMI classification and other variables was analysed using Kruskall-Wallis, Anova and Chi-Square tests. Then multivariate logistic regression was performed to establish the role of BMI in ACPA positivity and ordered logistic regression to establish its relationship with ACPA level. RESULTS: Among the patients studied, 255 (38.06%) were considered overweight and 136 (20.3%) obese. High BMI patients had significantly more pain perception and disability than normal weight patients, whereas no clear differences in disease activity were observed between high BMI and normal weight patients. ACPA positivity was significantly less frequent in overweight and obese patients compared to normal BMI patients. This information was confirmed by adjusting for smoking habit and the presence of shared epitope. CONCLUSIONS: Our data support the theory that high BMI patients suffer more frequently from ACPA-negative RA. Nevertheless, although no disease activity differences were observed, these patients showed higher pain and disability scores since the beginning of disease.
33379028 Microdevice immunoassay with conjugated magnetic nanoparticles for rapid anti-cyclic citru 2021 Mar 1 Anti-cyclic citrullinated peptide IgG antibodies (anti-CCP) are produced as an immune response in the presence of post-translational modified peptides known as cyclic citrullinated peptides (CCP). Anti-CCP have been considered as specific biomarkers for the diagnosis of rheumatoid arthritis (RA), and due to their high specificity, it is possible to make a differential diagnosis of other rheumatic diseases. These autoantibodies can be detected in the early stages of RA and even up to 10 years before presenting the first symptoms of the disease opening a window of opportunity for timely treatment. In this work, a simple straight channel microdevice and CCP conjugated magnetic nanoparticles (MNPs-CCP) as solid support was developed for quantifying anti-CCP. An additional microdevice with an optical flow Z cell design coupled with optical fibers was used to perform the spectrophotometric detection. The dynamic range of concentrations was determined between 0.70 and 2000 U mL(-1) with a limit of detection of 0.70 U mL(-1). The developed microdevice immunoassay was probed using a positive control and a negative control of plasma employing only 6 μL of both samples and reagents. The results showed that the proposed microdevice was almost nine times faster than using a commercial anti-CCP ELISA kit obtaining equivalent results and being 16 times more sensitive. The microdevice immunoassay, with conjugated MNPs-CCP is a simple method for anti-CCP quantification being cheaper, faster, and more sensitive than the ELISA kit.
32576051 The Association between the Plasma Sugar and Lipid Profile with the Gene Expression of the 2021 Aug BACKGROUND: Rheumatoid arthritis (RA) is an autoinflammatory and self-perpetuating disease with both articular and extra-articular manifestations, such as cardiovascular complications, which are the leading cause of mortality and morbidity in RA patients. Impaired sugar and lipid metabolism are considered as the critical risk factors for cardiovascular disease (CVD). Regarding the regulatory function of Raptor in the immunometabolism, in this study, we evaluated the association between plasma sugar and lipid profiles with the gene expression of Raptor and the cytokine tumor necrosis factor-α (TNF-α), as an inflammatory mediator, in peripheral blood leukocyte of RA patients. MATERIAL AND METHODS: Thirty-five RA patients who received combinational disease modified anti-rheumatoid drugs (DMARD) regimen and thirty healthy subjects enrolled in this study. The gene expression of Raptor was assessed by the real-time PCR method, and the Plasma levels of glucose and lipids, as well as TNF-α, were obtained using Hitachi device and enzyme-linked immunosorbent assay (ELISA) technique, respectively. RESULTS: The gene expression of Raptor was reduced significantly in RA patients compared to the healthy subjects (p = .001). The plasma level of HDL was significantly higher in RA patients than the control group (p = .001), while the plasma level of LDL was reduced significantly in these patients (p = .001). CONCLUSION: In our study, the reduced gene expression of Raptor may contribute to the impaired immunometabolism in RA patients, which is independent of plasma sugar and lipid profile.
32825978 Responsiveness of the Persian health assessment questionnaire measures in differentiating 2020 Jul OBJECTIVES: Evidence suggests that inflammation has a harmful effect on muscle strength as well as on functional disability. The purpose of the present study was to examine the association of objectively measured disease activity levels and functional disability among Iranian patients with Rheumatoid Arthritis (RA), and to analyse whether a Persian version of the health assessment questionnaire-disability index (PHAQ-DI) can distinguish between RA patients at different stages of the disease progression. MATERIALS & METHODS: 198 RA patients were requested to complete the PHAQ-DI. The disease activity score for each patient was evaluated using the disease activity score (DAS-28). The association analysis between the PHAQ-DI scores and the four levels of disease activity was measured using a Spearman correlation coefficient. A Kruskal-Wallis analysis was utilized to determine differences in PHAQ-DI scores among the levels of disease activity. The Receiver operating characteristic (ROC) curve was also utilized to determine the PHAQ-DI total score cut-off for predicting the level of disease activity. RESULTS: Spearman's correlation coefficients between the PHAQ-DI and the disease activity level ranged between 0.59 and 0.75. There were significant differences in the PHAQ-DI total score among known groups with various disease activity levels (P = 0.001); However, HAQ-DI total score could not differentiate the remission phase from low disease activity levels in patients with RA (p = 0.37). The PHAQ-DI total score cut-off for distinguishing remission-low disease activity from moderate-high disease activity was 1.19, with a specificity of 0.91 and a sensitivity of 0.615. CONCLUSION: The present findings provide evidence for the degree to which the PHAQ-DI measures identify and distinguish disease activity levels in patients with rheumatoid arthritis. The PHAQ-DI questionnaire, as a patient-administered, non-invasive, fast, inexpensive and available tool, can be used in the rheumatologist's office as a substitute for determining disease activity in patients with active RA.
32815001 Polymorphisms within the RANK and RANKL Encoding Genes in Patients with Rheumatoid Arthrit 2020 Aug 19 Inconsistency of the results regarding the genetic variability within genes coding for receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) in rheumatoid arthritis (RA) prompted us to study the RANK and RANKL polymorphisms as potential biomarkers associated with disease predisposition and response to anti-TNF treatment in a group of Polish patients with RA. This study enrolled 318 RA patients and 163 controls. RANK (rs8086340, C > G; rs1805034, C > T) and RANKL (rs7325635, G > A; rs7988338 G > A) alleles were determined by real-time PCR with melting curve analysis and related with clinical parameters. In addition, RANKL serum levels were measured by ELISA. The RANK rs8086340-G allele was overrepresented among patients as compared to controls (OD = 1.777, p = 0.038). C-reactive protein (CRP) levels were significantly (p < 0.05) associated with RANK rs8086340 polymorphism and were higher in the CC-homozygotes at the baseline while lower in the GG-carriers at the 12th week of the treatment. At the latter time point RANKL rs7325635-GG-positive patients also showed significantly lower CRP concentrations. Higher alkaline phosphatase levels before induction of anti-TNF therapy were observed in RANK rs8086340 and RANK rs1805034 CC homozygotes (p = 0.057 and p = 0.035, respectively). The GG homozygosity of both RANKL single nucleotide polymorphisms was significantly associated with the number of swollen joints (rs7988338 and rs7325635, before and at the 12th week of therapy, respectively, p < 0.05 in both cases). These results imply that polymorphisms within the RANK and RANKL genes affect RA susceptibility and anti-TNF treatment outcome.