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ID PMID Title PublicationDate abstract
33387686 Type 1 helper T cells generate CXCL9/10-producing T-bet(+) effector B cells potentially in 2021 Feb Efficacy of B-cell depletion therapy highlights the antibody-independent effector functions of B cells in rheumatoid arthritis (RA). Given type 1 helper T (Th1) cells abundant in synovial fluid (SF) of RA, we have determined whether Th1 cells could generate novel effector B cells. Microarray and qPCR analysis identified CXCL9/10 transcripts as highly expressed genes upon BCR/CD40/IFN-γ stimulation. Activated Th1 cells promoted the generation of CXCL9/10-producing T-bet(+) B cells. Expression of CXCL9/10 was most pronounced in CXCR3(+) switched memory B cells. Compared with peripheral blood, SFRA enriched highly activated Th1 cells that coexisted with abundant CXCL9/10-producing T-bet(+) B cells. Intriguingly, anti-IFN-γ antibody and JAK inhibitors significantly abrogated the generation of CXCL9/10-producing T-bet(+) B cells. B cell derived CXCL9/10 significantly facilitated the migration of CD4(+) T cells. These findings suggest that Th1 cells generate the novel CXCL9/10-producing T-bet(+) effector B cells that could be an ideal pathogenic B cell target for RA therapy.
34016004 Time-of-day effects on the postural control and symptoms in women with rheumatoid arthriti 2021 Sep The present study was designed to assess time-of-day effects on postural balance and symptoms of rheumatoid arthritis (RA) patients. A total of 15 American College of Rheumatology functional class I and II RA patients and 15 healthy controls aged between 45 and 55 (mean age: 50 ± 3) years of age voluntarily participated. We conducted a case-control, repeated-measures in design study. Postural balance, axillary temperature, pain intensity, fatigue, and sleepiness were measured during five test sessions at 06:00, 10:00, 14:00, 18:00, and 22:00 h. Participants were randomized to the order of test sessions, and each session was separated by >36 hours to minimize/eliminate learning effects. Center of pressure area (CoP(area)) (p < .001), pain (p < .01), and sleepiness (p < .05) values were significantly higher at 06:00 and 22:00 h compared to 10:00, 14:00, and 18:00 h in the RA group. Fatigue significantly increased (p < .05) at 22:00 h in comparison to 10:00, 14:00, and 18:00 h in the RA group. Axillary temperature was significantly (p < .001) lower at 06:00 and at 22:00 h compared to 10:00, 14:00, and 18:00 h in the RA group. In the control group, there were no significant time-of-day difference in fatigue, but axillary temperature was significantly lower (p < .01) at 06:00 h compared to 10:00 h, 14:00, 18:00, and 22:00 h, sleepiness values were significantly higher (p < .05) at 06:00 and 22:00 h compared to 10:00, 14:00, and 18:00 h, and revealed CoP(area) values were significantly (p < .05) higher at 06:00 h compared to 14:00 h. Finally, in the RA group, significant correlations were found between values of CoP(area) and pain (r = 0.47; p < .001), sleepiness (r = 0.39; p < .01), fatigue (r = -0.46; p < .001), and also axillary temperature (r = -0.35; p < .001). Multiple linear regression analysis further indicated that in the RA group, time-of-day variation in postural balance was predicted collectively by that in pain and fatigue (30.7%) (R2 = 0.307; F = 11.53; p < .001). Our results first suggest that time-of-day significantly affects postural balance, axillary temperature, pain intensity, fatigue, and sleepiness in RA patients and second that the temporal variation observed in pain, fatigue, and somnolence are concomitant with that observed in postural balance.Abbreviations: RA: Rheumatoid arthritis; H&O questionnaire: Horne and Ostberg questionnaire; PSQI: Pittsburgh sleep quality index; HAQ: Health assessment questionnaire; SF-36: the short form-36; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; CoP: The Center of foot Pressure; CoP(area): The Center of foot Pressure area; VAS: The Visual Analogue Scale; KSS: Karolinska Sleepiness Scale.
34050440 Advanced glycation end products, advanced oxidation protein products, and ferric reducing 2021 Oct BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory disorder causing functional disabilities. Oxidative stress can cause inflammation and can also be induced by inflammation. Measuring oxidative stress markers could help better understand the pathophysiology of RA and may be used to define the disease severity. MATERIAL AND METHOD: In this case-control study, 75 RA patients were selected among those referred to the rheumatology clinic. Patients were further categorized into two groups, with active and inactive disease according to the Disease Activity Score (DAS) 28. Forty healthy volunteered persons were selected as the control group. Blood samples were obtained, and advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), and ferric reducing ability of plasma (FRAP) were measured. The results were compared via student t-test and Chi-square. RESULTS: Mean ± SD values for AGEs, AOPP, and FRAP in cases and controls were 53.29 ± 6.82 vs. 44.43 ± 7.13 (p = 0.001), 146.08 ± 19.56 vs. 135.79 ± 14.23 (p = 0.004), and 967.13 ± 226.66 vs. 1012.87 ± 215.94 (p = 0.2), respectively. Mean ± SD values for AGEs, AOPP, and FRAP in patients with active disease and inactive disease were 53.32 ± 7.2 vs. 53.26 ± 6.48 (p = 0.9), 146.97 ± 17.56 vs. 145.06 ± 21.84 (p = 0.6), and 953.17 ± 217.09 vs. 983.09 ± 239.31 (p = 0.5), respectively. CONCLUSION: AGEs and AOPP but not FRAP were significantly increased in RA patients compared to healthy controls. There was no significant difference between AGEs, AOPP, and FRAP in RA patients with active and inactive disease. Key points • AGEs and AOPP but not FRAP were significantly increased in RA patients compared to healthy controls. • There was no significant difference between AGEs, AOPP, and FRAP in RA patients with active and inactive disease.
34504225 Association between 9-month isoniazid prophylaxis of latent tuberculosis and severe hepati 2021 Sep 9 To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan's National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1-28, 29-56, 57-84, 85-168, 169-252, and 253-280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients' baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57-16.55), especially 57-84 days (IRR: 17.29, 95% CI: 3.11-96.25) and 85-168 days (IRR:10.55, 95% CI: 1.90-58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57-168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.
33860755 Comparison of the efficacy and safety of tofacitinib and mavrilimumab in patients with act 2021 Aug OBJECTIVES: The relative efficacy and safety of tofacitinib and mavrilimumab were assessed in patients with rheumatoid arthritis (RA) presenting an inadequate response to disease-modifying antirheumatic drugs (DMARDs). MATERIALS AND METHODS: We performed a Bayesian network meta-analysis combining direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and mavrilimumab combined with DMARDs in patients with an inadequate response to DMARDs. RESULTS: In total, 8 RCTs with 2,965 patients met inclusion criteria. 21 pairwise comparisons were performed, including 12 direct comparisons of 7 interventions. In patients with active RA and an inadequate DMARD response, mavrilimumab 150 mg+methotrexate (MTX) and mavrilimumab 100 mg+MTX were the most effective treatments. Compared with placebo+MTX, all tofacitinib and mavrilimumab doses, except mavrilimumab 50 mg+MTX, achieved significant ACR20 responses. The ranking probability based on the surface under the cumulative ranking curve indicated that mavrilimumab 150 mg+MTX had the highest probability for best treatment outcome in terms of the ACR20 response rate, followed by mavrilimumab 100 mg+MTX, tofacitinib 10 mg+MTX, tofacitinib 5 mg+MTX, mavrilimumab 30 mg+MTX, mavrilimumab 50 mg+MTX, and placebo+MTX. No significant differences were noted in the incidence of serious adverse events (SAEs) after tofacitinib+MTX, mavrilimumab+MTX, or placebo+MTX. CONCLUSION: In patients with RA showing inadequate DMARD response, mavrilimumab 150 mg+MTX and mavrilimumab 100 mg+MTX, followed by tofacitinib 10 mg+MTX and tofacitinib 5 mg+MTX, were the most efficacious interventions and were not associated with a significant risk of SAEs.
32947399 Descemet Stripping Endothelial Keratoplasty Outcomes in Patients With Rheumatoid Arthritis 2021 Aug 1 PURPOSE: To review the graft and visual outcomes in a series of patients with rheumatoid arthritis (RA) who underwent Descemet stripping endothelial keratoplasty (DSEK). METHODS: In this case series, the electronic medical records at Wills Eye Hospital were queried for cases of patients with RA who underwent DSEK between January 1, 2009 and September 1, 2018. Charts were reviewed to obtain demographic data, medical history, ocular history, surgical variables, graft survival, and visual acuity outcomes. RESULTS: During the study period, 22 transplants performed in 18 eyes of 15 patients with RA were eligible for inclusion. The mean age at the time of initial DSEK was 70.5 ± 11.1 years (range 46-87). The mean follow-up time for the included eyes was 4.89 ± 2.71 years (range 1.95-10.39). The overall estimated graft survival was 8.26 ± 0.81 years with a 5-year survival rate of 88.9%. A significant improvement from preoperative best corrected visual acuity (logarithm of the minimum angle of resolution 0.84, approximately 20/140) to the most recent follow-up (logarithm of the minimum angle of resolution 0.29, approximately 20/40) was noted (P < 0.001). CONCLUSIONS: In our case series, patients with a history of RA underwent successful DSEK with excellent graft survival rates and visual acuity outcomes. Well-controlled RA should therefore not be considered a deterrent to performing DSEK.
32452354 The mRNA levels of TGF-β Type II receptor splice variants in monocytes are associated wit 2021 Mar OBJECTIVES: In rheumatoid arthritis (RA) patients, TGF-β exerts a singular effect on lymphocytes, macrophages, and polymorphonuclear leukocytes. Moreover, evidences indicate that TGF-β1 stimulation affects the expression levels of TGF-β receptors. Therefore, we analysed in different leukocyte subpopulations, whether the mRNA abundance of TGFBR2 splice variants might be related to RA. METHODS: We isolated different leukocyte subpopulations from peripheral blood from 9 healthy control volunteers and 9 RA patients, matched by gender and age (cohort 1), and 8 additional RA patients (cohort 2). Then we quantified, by RT-qPCR, the mRNA relative abundance of TGFBR2 splice variants (namely TGFBR2A and TGFBR2B) in PMNs, and PBMCs (monocytes and non-monocytes). We first checked whether the TGFBR2-splice variant mRNA profile could be associated with any particular blood cell type both, in healthy control volunteers and in RA patients. In addition, PBMC and PMN mRNA levels were correlated, using Spearman's rank-order correlation test, with clinical and biochemical determinations of RA patients. RESULTS: We have shown that TGFBR2 exhibits an alternative splicing pattern in different subpopulations of human leucocytes from healthy controls, and the lack of it in the same cell type from RA samples. Furthermore, our study yields initial evidence that TGFBR2 mRNA expression levels in monocytes might mirror RA disease activity. CONCLUSIONS: mRNA abundance of TGFBR2 splice variants in monocytes shows changes linked to RA disease activity.
32591174 Anterior placement of the talar component in total ankle arthroplasty: A risk factor for t 2021 Apr BACKGROUND: Component subsidence is considered as a cause of revision surgery. The talar component subsidence may be a risk factor for revision surgery; however, there are no reports regarding talar component placement and subsidence amount following total ankle arthroplasty (TAA). We therefore investigated the relationship between talar component placement and subsidence amount. METHODS: Fifty-two ankles from 49 patients (age: 71 years [range 62-83], 13 male/ 36 female), who underwent TAA with mean follow-up of 36 months (range 12-83), were included. The subjects were divided into two groups based on talar component placement: anterior placement (n = 20, group A) and posterior placement (n = 32, group P) using weight-bearing lateral plain radiographs. The amount of the talar component subsidence and clinical outcomes, which included the Japanese Society for Surgery of the Foot (JSSF) scale, range of the motion (ROM) and the revision rate, were compared between the groups. RESULTS: Talar component subsidence was significantly higher in group A (2.1 ± 2.0 mm) than in group P (0.6 ± 1.4 mm, P = .017). There was no significant difference in the JSSF scale and ROM between group A and group P. The revision rate was 10.0% in group A and 6.3% in group P, albeit not statistically significant. CONCLUSION: Greater talar component subsidence was observed when the talar component was placed more anteriorly, suggesting that anterior placement of the talar component may need to be avoided during the surgery in order to minimize the postoperative talar component subsidence.
31961487 Elevated Anti-Citrullinated Protein Antibodies Prior to Rheumatoid Arthritis Diagnosis and 2021 Apr OBJECTIVE: To investigate elevation of anti-citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma. METHODS: We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors. Pre-RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (HRs) for incident COPD or asthma (in separate analyses) associated with pre-RA, pre-RA ACPA+, or pre-RA ACPA- phenotypes each compared to their matched non-RA controls. RESULTS: We analyzed 283 women who were pre-RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years before RA diagnosis. Fifty-nine women (20.8%) were pre-RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person-years of follow-up. Pre-RA ACPA+ was associated with increased COPD risk (HR 3.04 [95% confidence interval (95% CI) 1.33-7.00]) after adjusting for covariates including smoking pack-years. Pre-RA ACPA+ had an HR for asthma of 1.74 (multivariable 95% CI 0.72-4.24), similar to the risk of asthma for pre-RA ACPA- (HR 1.65 [95% CI 1.11-2.46]). CONCLUSION: Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma than controls, regardless of pre-RA ACPA status.
34877355 Cost-Effectiveness Analysis of Biopharmaceuticals for Treating Rheumatoid Arthritis: Infli 2021 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease that causes joint destruction. The condition imposes a significant economic burden on patients and societies. The present study is aimed at evaluating the cost-effectiveness of Infliximab, Adalimumab, and Etanercept in treating rheumatoid arthritis in Iran. METHODS: This is a cost-effectiveness study of economic evaluation in which the Markov model was used. The study was carried out on 154 patients with rheumatoid arthritis in Fars province taking Infliximab, Adalimumab, and Etanercept. The patients were selected through sampling. In this study, the cost data were collected from a community perspective, and the outcomes were the mean reductions in DAS-28 and QALY. The cost data collection form and the EQ-5D questionnaire were also used to collect the required data. The results were presented in the form of an incremental cost-effectiveness ratio, and the sensitivity analysis was used to measure the robustness of the study results. The TreeAge Pro and Excel softwares were used to analyze the collected data. RESULTS: The results showed that the mean costs and the QALY rates in the Infliximab, Adalimumab, and Etanercept arms were $ 79,518.33 and 12.34, $ 91,695.59 and 13.25, and $ 87,440.92 and 11.79, respectively. The one-way sensitivity analysis confirmed the robustness of the results. In addition, the results of the probabilistic sensitivity analysis (PSA) indicated that on the cost-effectiveness acceptability curve, Infliximab was in the acceptance area and below the threshold in 77% of simulations. The scatter plot was in the mentioned area in 81% and 91% of simulations compared with Adalimumab and Etanercept, respectively, implying lower costs and higher effectiveness than the other two alternatives. Therefore, the strategy was more cost-effective. CONCLUSION: According to the results of this study, Infliximab was more cost-effective than the other two medications. Therefore, it is recommended that physicians use this medication as the priority in treating rheumatoid arthritis. It is also suggested that health policymakers consider the present study results in preparing treatment guidelines for RA.
33544235 The role of extracellular vesicles in rheumatoid arthritis: a systematic review. 2021 Sep Rheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not been completely elucidated yet. Extracellular vesicles (EVs) are membrane-contained vesicles released by cells playing a role in cell-to-cell communication and they could be involved in different diseases. Evidence on the involvement of EVs in RA is currently inconclusive. Therefore, a systematic review on the role of EVs in RA was performed in order to explore this relationship. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research was conducted on PubMed, Scopus, and Embase up to March 5, 2020: 41 studies were analyzed out of 674 screened. The total plasmatic and synovial fluid (SF) EV number seems increased in RA as compared with healthy controls. Both RA plasma and SF contained EVs subpopulations of heterogenous origin, especially derived from platelets and immune system cells. No univocal evidence emerged on miRNA expression and EV content profile within RA patients. EVs showed to enhance pro-inflammatory pathways, such as cytokines and chemokine release and TNF blockade seemed to revert this effect. Our work highlights the requirement to standardize study methodologies in order to make results comparable and draw conclusions that remain, at present, unclear.
34960085 Assessment of Intramuscular Fat and Correlation with Body Composition in Patients with Rhe 2021 Dec 17 Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are associated with changes in body composition. Ectopic intramuscular fat (IMAT) may alter muscle function and contribute to cardiometabolic disorders. In a pilot study, we analyzed IMAT in the calf with peripheral quantitative computed tomography (pQCT) and examined correlations between IMAT quantity and body composition parameters. In 20 patients with active RA and 23 with active SpA, IMAT was correlated with visceral fat (VAT; r = 0.5143 and 0.6314, respectively; p < 0.05) and total lean mass (r = 0.5414 and 0.8132, respectively; p < 0.05), but not with whole body fat mass. Total lean mass mediated 16% and 33% of the effects of VAT on IMAT in RA and SpA, respectively. In both RA and SpA, calf muscle area was correlated with total lean mass (r = 0.5940 and r = 0.8597, respectively; p < 0.05) and fat area was correlated with total body fat (r = 0.6767 and 0.5089, respectively; p < 0.05) and subcutaneous fat (r = 0.6526 and 0.5524, respectively; p < 0.05). Fat area was inversely correlated with handgrip and walking tests, and it was associated with disease activity and disability. We showed that ectopic IMAT, measured with pQCT, was correlated with VAT, but not with total body fat, in RA and SpA. This result suggests that metabolically active fat was specifically associated with IMAT.
34180145 CIITA gene polymorphism (rs3087456) in systemic lupus erythematosus and rheumatoid arthrit 2021 Oct Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co-activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (-168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations.
33707573 Red meat intake is associated with early onset of rheumatoid arthritis: a cross-sectional 2021 Mar 11 Accumulating evidence has implicated dietary factors as important risks for rheumatoid arthritis (RA) development, but analyses of the effects of red meat consumption on RA have yielded diverging results. The aim of this study was to explore the association between red meat and RA in a large-scale, cross-sectional study. From June to December 2016, a total of 733 patients were investigated, from which 707 participants were included in the analysis. These patients were divided into two groups according to their consumption of red meat (< 100 g/day; ≥ 100 g/day). The intake of red meat was assessed via physician-administered questionnaire. Generalized linear models were used to analyze relationships between the red meat intake and RA, adjusting for potential confounders including demographic, clinical, laboratory, and other dietary factors. Compared with low-intake red meat RA patients, high-intake red meat patients had an earlier onset age (p = 0.02) and had higher BMI (p = 0.003). The age at disease onset for the high-intake patients was 6.46 years earlier than for low-intake patients, after adjustment for demographic and other possible confounders (β = - 6.46, 95% CI - 9.77, - 3.15; p = 0.0001). Further, stratified analyses showed that this inverse association of red meat intake with RA onset age was especially evident in smokers and overweight patients (BMI ≥ 24 kg/m(2)). In conclusion, high-intake red meat is associated with early onset of RA, especially in smokers or overweight patients. The findings indicate that eating less red meat could be a recommendation given to patients at risk for RA development.
32573414 The effect of methotrexate on neutrophil reactive oxygen species and CD177 expression in r 2021 May OBJECTIVES: Neutrophils are found in abundance in the synovial fluid of patients with rheumatoid arthritis (RA), where they are activated and show high reactive oxygen species (ROS) production. However, there is limited data on circulating neutrophils in peripheral blood of patients with RA in terms of ROS production, expression of activation markers and the effect of treatment with methotrexate (MTX) on ROS. METHODS: This single-centre prospective study recruited patients of RA classified as per the 2010 ACR/EULAR criteria. In the cross-sectional arm, we included three groups, treatment-naïve RA (naïve-RA), MTX-treated RA (MTX-RA) and healthy controls, and compared ROS production and surface markers of neutrophil activation. In the longitudinal arm, we studied the change in neutrophil ROS production after 8 weeks of MTX treatment in naïve-RA patients. Neutrophil ROS production was measured by flow cytometry using dihydrorhodamine-123 (DHR) and by chemiluminescence using luminol. Surface expression of CD177, CD11b and CD64 was measured by flow cytometry. RESULTS: This study included 103 patients (50 naïve-RA, 53 MTX-RA) and 20 controls. Both naïve-RA and MTX-RA patients showed higher ROS production than healthy controls in unstimulated neutrophils in the DHR assay (p<0.001 and p=0.004). MTX-RA patients showed significantly lower ROS production than naive-RA, in both unstimulated (p=0.004) and PMA-stimulated neutrophils in the DHR assay (p=0.03). On longitudinal follow-up of 24 naïve-RA patients, there was a significant reduction of neutrophil ROS production (by 55% from baseline) (p<0.001) after 8 weeks of MTX. Neutrophil CD177 expression was higher in both naïve-RA and MTX-RA (trend) than controls (p=0.001 and p=0.09). MTX-RA neutrophils showed lower expression of CD177 than naïve-RA (p=0.01). CD11b expression was higher in MTX-RA compared to controls (p=0.01). CONCLUSIONS: Circulating neutrophils in RA showed higher ROS production and higher expression of CD177 and CD11b compared to controls. MTX treatment was associated with a reduction in ROS production and CD177 expression, which may be one of the mechanisms by which MTX works in RA.
34201546 Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Ration 2021 Jun 23 Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are two cytokines involved in the perpetuation of the chronic inflammation state characterizing rheumatoid arthritis (RA). Significant advances in the treatment of this pathology have been made over the past ten years, partially through the development of anti-TNF and anti-IL-1 therapies. However, major side effects still persist and new alternative therapies should be considered. The formulation of the micro-immunotherapy medicine (MIM) 2LARTH(®) uses ultra-low doses (ULD) of TNF-α, IL-1β, and IL-2, in association with other immune factors, to gently restore the body's homeostasis. The first part of this review aims at delineating the pivotal roles played by IL-1β and TNF-α in RA physiopathology, leading to the development of anti-TNF and anti-IL-1 therapeutic agents. In a second part, an emphasis will be made on explaining the rationale of using multiple therapeutic targets, including both IL-1β and TNF-α in 2LARTH(®) medicine. Particular attention will be paid to the ULD of those two main pro-inflammatory factors in order to counteract their overexpression through the lens of their molecular implication in RA pathogenesis.
32985955 Immunoglobulin D-kappa multiple myeloma in a patient with rheumatoid arthritis: a case rep 2021 Jan A 77-year-old Japanese woman with a 21-year history of seropositive, erosive rheumatoid arthritis (RA) and a 10-year history of methotrexate (MTX) therapy was admitted with malaise and mild consciousness disturbance. Laboratory data showed hypercalcemia, acute kidney injury, normocytic anaemia, and thrombocytopenia. As we first assumed drug-induced toxicity by MTX and eldecalcitol, both were discontinued and leucovorin rescue therapy and calcitonin were administered. However, her condition continued to worsen. Serum protein electrophoresis showed only a small M-peak, immunoelectrophoresis of both the serum and urine demonstrated Bence-Jones kappa (κ) type monoclonal protein without immunoglobulin heavy chain, and bone marrow examination revealed proliferation of plasma cells. We diagnosed her with Bence-Jones κ type multiple myeloma (MM) and transferred her to the department of haematology of a higher order medical institution. Conclusively, the diagnosis of immunoglobulin (Ig) D-κ type MM, a rare variant of this disorder, was determined in accordance with serum immunofixation. Several previous studies have suggested that pre-existing RA is a risk factor for MM. Although IgD MM is characterised by its clinical severity and poor prognosis compared to other subtypes, it is often misdiagnosed or mistaken as light chain type MM, as in the present case, because of the low level of IgD M-protein, resulting in delayed diagnosis. Physicians must take MM into consideration as a differential diagnosis when inactive RA patients present with inexplicable elevated calcium, renal failure, anaemia, and bone lesion symptoms and should be aware of IgD MM to establish the correct diagnosis promptly.
33500279 Lifestyle factors associated with incidence of rheumatoid arthritis in US adults: analysis 2021 Jan 26 OBJECTIVE: To quantify rheumatoid arthritis (RA) cases attributable to selected non-genetic risk factors. DESIGN: National Health and Nutrition Examination Survey (NHANES) and meta-analysis. PARTICIPANTS: US adults. DATA SOURCES: The prevalence of exposure was obtained from NHANES. Weighted analysis was performed to account for the complex sampling design in NHANES. PubMed and Web of Science up to 31 March 2019 were searched to identify epidemiological studies reported the association between non-genetic risk factors and RA in US adults. Relative risk (RR) value and the corresponding CI were pooled by meta-analysis to evaluate the associations between modifiable risk factors and RA. Population attributable fraction (PAF) was calculated based on the prevalence and RR data. RESULTS: The weighted percentages of former smokers, current smokers and overweight or obese people were 24.84%, 23.93% and 63.97%, and the average alcohol consumption was 51.34 g/week. In the meta-analysis, we found that former smokers (RR 1.22, 95% CI 1.10 to 1.36) and current smokers (RR 1.47, 95% CI 1.29 to 1.68) had higher risks of RA. Overweight and obese individuals had 1.27-fold (95% CI 1.09 to 1.48) increased risk of RA. Each per 50 g/week increment of alcohol consumption was associated with 8% (95% CI 0% to 16%) reduction in the risk of RA. Therefore, PAF value of smoking was 14.00% (95% CI 8.13% to 23.33%). Excess body mass index (BMI) was found to account for 14.73% (95% CI 5.45% to 23.50%) of RA incidence. The fraction of RA risk attributed by low alcohol intake was 8.21% (95% CI 0.31% to 16.39%). Collectively, we found that 32.69% (95% CI 13.41% to 50.96%) of RA cases were attributable to smoking, overweight or obesity and low alcohol drinking. CONCLUSION: Nearly 33% of RA incidence was attributed to smoking, excess BMI and low alcohol drinking in USA. Our findings could provide a basis for developing guidelines of RA prevention and control in USA.
34909885 Characterization of clinical, laboratory, IL-6 serum levels, and IL-6-174 G/C genetic poly 2021 Nov OBJECTIVE: This study aimed to characterize the clinical (disease activity and exocrine gland function), laboratory, interleukin 6 (IL-6) serum levels, and IL-6-174G/C (rs1800795) genetic polymorphisms among rheumatoid arthritis (RA), RA plus Sjögren's syndrome (RA+SS), and control subjects. METHODS: A case-control study enrolling 137 women (52±11 years old) were divided into three groups as follows: RA (n=70), RA+SS (n=29), and healthy control (C, n=38). Individuals underwent clinical evaluation composed of Schirmer's test, unstimulated salivary flow rate, and evaluation of disease activity and functional capacity (Disease Activity Score [DAS28] and Health Assessment Questionnaire [HAQ]). IL-6 serum levels and IL-6-174G/C polymorphisms were assessed. RESULTS: RA and RA+SS presented higher serum levels of IL-6 than controls (p<0.001). Also, higher IL-6 levels were related to swollen joints (p=0.038), limited functional capacity (p=0.004), and disease activity (p≤0.001). However, neither IL-6-174G/C genetic polymorphism nor its allele frequency was associated with RA or RA+SS. CONCLUSION: IL-6 serum is an important marker of RA activity and functional incapacity, but IL-6-174G/C genetic polymorphism did not differ among healthy controls and cases.
33049484 Association between traffic-related air pollution and hospital readmissions for rheumatoid 2021 Jan 1 Air pollution is an important risk factor for autoimmune diseases, but its association with the recurrence of rheumatoid arthritis (RA) remains unclear so far. This study aimed to investigate the short-term association between traffic-related air pollutants and hospital readmissions for RA in Hefei, China. Data on daily hospital readmissions for RA and traffic-related air pollutants, including particulate matter (PM(2.5) and PM(10)), nitrogen dioxide (NO(2)), and carbon monoxide (CO), from 2014 to 2018 were retrieved. A time-series approach using generalized linear regression model was employed. The analysis was further stratified by sex, age and season. A total of 1153 readmissions for RA were reported during the study period. A significant association between high-concentration PM(2.5) (90th percentile) and RA readmissions was observed on lag1 (relative risk (RR) = 1.09, 95% confidence interval (CI): 1.01-1.19) and lasted until lag3 (RR = 1.06, 95%CI: 1.01-1.12). From lag2 to lag5, high-concentration NO(2) (90th percentile) was associated with increased risk of RA readmissions, with the highest RR observed at lag 4 (1.11, 95%CI: 1.05-1.17). Stratified analyses indicated that females and the elderly appeared to be more vulnerable to high-concentration PM(2.5) and NO(2) exposure. High-concentration PM(2.5) and NO(2) in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM(2.5) and NO(2) was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM(2.5) and NO(2) should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons.