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ID PMID Title PublicationDate abstract
32598777 [Assessment of the safety, tolerability and effectiveness of first Russian generic aceclof 2020 Jun 5 AIM: To evaluate the effectiveness and tolerability of the drug in patients with undifferentiated peripheral inflammatory arthritis (UPIA). MATERIALS AND METHODS: We observed 60 patients (39 women and 21 men) met G. Hazlewood et al., UPIA criteria, 2011. Patients were divided into 3 groups: with monoarthritis, oligoarthritis and polyarthritis. They took aceclofenac 100 mg twice day for 3 weeks. RESULTS: We noted significant decreasing in pain level according to visual analogue scale: in patients with monoarthritis by 69.3 mm (p0.001); in oligoarthritis group by 47.5 mm (p0.001), in patients with polyarthritis by 30 mm (p0.001). The life quality by the EQ-5D-5L index was improved too in all groups from 0.616 to 0.829 (p0.001). The satisfaction with the therapy was: in monoarthritis patients (80% of patients and 93% of doctors noted good results), in oligoarthritis group (53% and 39% accordingly) and polyarthritis (74% and 64% respectively). We suppose the difference was due to the fact that mono- and oligoarthritis patients suffered from initial forms of seronegative spondylarthropathy, in which the effectiveness of NSAIDs is traditionally higher; polyarthritis patients probably had debut of rheumatoid arthritis. Adverse events of therapy were mild. We noted gastrointestinal tract symptoms (dyspepsia) and increased ALT in 10 patients and increased blood pressure in 1 patient. The symptoms did not require discontinuation of therapy. Сonclusion. Post-registration observational study of first Russian generic aceclofenac (Alental, Vertex, Russia) was conducted. In UPIA patients aceclofenac therapy was most effective in mono- and oligoarthritis patients. The first Russian generic aceclofenac (Alental, Vertex, Russia) has good efficacy, tolerability and safety and can be recommended for arthritis treatment.
32701988 Development and validation of a questionnaire assessing household work limitations (HOWL-Q 2020 INTRODUCTION: Rheumatoid arthritis (RA) has female preponderance and interferes with the ability to perform job roles. Household work has 2 dimensions, paid and unpaid. There is not a validated instrument that assesses the impact of RA on limitations to perform household work. We report the development and validation of a questionnaire that assesses such limitations, the HOWL-Q. METHODS: The study was performed in 3 steps. Step-1 consisted on HOWL-Q conceptual model construction (literature review and semi-structured interviews to 20 RA outpatients and 20 controls, household workers, who integrated sample (S)-1). Step-2 consisted of instructions selection (by 25 outpatients integrating S-2), items generation and reduction (theory and key informant suggestions, modified natural semantic network technique, and pilot testing in 200 household workers outpatients conforming S-3), items scoring, and questionnaire feasibility (in S-3). Step-3 consisted of construct (exploratory factor analysis) and criterion validity (Spearman correlations), and HOWL-Q reliability (McDonald's Omega and test-retest), in 230 household work outpatients integrating S-4. RESULTS: Patients conforming the 4 samples were representative of typical RA outpatients. The initial conceptual model included 8 dimensions and 76 tasks/activities. The final version included 41 items distributed in 5 dimensions, was found feasible and resulted in 62.46% of the variance explained: McDonald's Omega = 0.959, intraclass-correlation-coefficient = 0.921 (95% CI = 0.851-0.957). Moderate-to-high correlations were found between the HOLW-Q, the HAQ, the Quick-DASH and the Lawton-Brody index. HOWL-Q score ranged from 0 to 10, with increasing scores translate into increase limitations. CONCLUSION: The HOWL-Q showed adequate psychometric properties to evaluate household work limitations in women with RA.
32220060 Lung cancer in patients with and without rheumatoid arthritis: A propensity score-matched 2020 Jun BACKGROUND: Connective tissue disease increases the risk of lung cancer, but whether rheumatoid arthritis (RA) has an effect on the overall survival (OS) rate in this population has not been well studied. METHODS: Patients diagnosed with lung cancer between January 2015 and December 2017 were enrolled in this retrospective analysis. Propensity score matching was performed to balance the baseline of the two groups, whereas the differences between patients with and without RA were compared using survival analysis. Further, the effects of interstitial lung disease (ILD) and qi deficiency on survival in cases of RA with lung cancer were examined. Cox regression analysis was applied to predict the factors that influenced the survival of lung cancer to one year. RESULTS: Overall, 154 lung cancer patients, including 136 (88.3%) without RA and 18 (11.7%) with RA, were included. Two comparison cohorts were matched by 1:2 propensity score matching, which yielded 18 lung cancer patients with RA and 36 lung cancer patients without RA. Ultimately, the survival prognosis of lung cancer and RA was worse than that without RA, that of patients with ILD with RA and lung cancer was worse than that among those without RA, and that of patients with qi deficiency with RA and lung cancer was worse than that among those without RA. CONCLUSIONS: The survival prognosis of lung cancer patients with RA is worse than that of those without RA. ILD and qi deficiency promote reduced survival when found in conjunction with RA in patients with lung cancer.
32289665 LncRNA LINC-PINT increases SOCS1 expression by sponging miR-155-5p to inhibit the activati 2020 Jul Rheumatoid arthritis (RA) is a systemic and chronic autoimmune disease associated with altered gene expression in synovial tissue. Long intergenic non-protein encoding long-chain RNA p53-induced transcript (LncRNA LINC-PINT) has been reported to be involved in multiple physiological and pathological processes. However, the role of lncRNA LINC-PINT in RA is rarely mentioned. To investigate the mechanism of LINC-PINT in RA, we constructed a RA model using TNF-α-induced method to explore the downstream effector and signaling pathway. We found that LINC-PINT was downregulated in RA tissues and TNF-α stimulated RA cells. And overexpression of LINC-PINT could inhibit cell proliferation and invasion induced by TNF-α through downregulating the levels of IL-1β and MMPs and inhibiting the activation of ERK pathway. Using bioinformatics analysis and RNA Binding Protein Immunoprecipitation (RIP) assay, we verified that LINC-PINT directly interacted with miR-155-5p, and miR-155-5p could regulate the expression of SOCS1. Whereas, downregulation of miR-155-5p inhibited cell growth and invasion. Overexpression of miR-155-5p could reverse the inhibitory effect of LINC-PINT induced by TNF-α. Furthermore, silencing SOCS1 promoted cell proliferation and invasion, upregulated the expression of IL-1β and MMPs, and activated ERK pathway, while overexpression of LINC-PINT could reverse the control of knocking down SOCS1. In conclusion, we revealed that LINC-PINT suppressed TNF-α induced cell proliferation and invasion which might be induced through downregulating miR-155-5p, influencing the expression of SOCS1, IL-1β and MMPs and inactivating ERK signaling pathway.
34756317 «Living with rheumatoid arthritis» in an indigenous qom population in Argentina. A quali 2021 Nov INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease which impacts patients' quality of life. The prevalence of RA in the qom population was 2.4% and represented an aggressive and disabling disease. The study goal was to describe the experience of the indigenous qom community individual suffering from RA, along with their experience with the local health care system in the city of Rosario, Santa Fe, Argentina. METHODS: Qualitative Study using techniques of participant observation and semi-structured interviews; following a guideline developed by a multidisciplinary research group comprising anthropologists, rheumatologists, nurses, and psychologists. A triangulation strategy was implemented for the analysis. RESULTS: A total of 33 interviews were conducted in 29 individuals with RA. The results showed a "normalization" of their symptoms and of their limitations in performing daily tasks. The individuals' relationship with the local health care system was complex and limited in several aspects (e.g. access to health care, continuity of treatment, complexity of medical care pathway and lack of cultural competence). CONCLUSIONS: RA is a disease that has a negative impact on the daily lives of the qom people living in Rosario. Improving the relationship between this population and the local health care system as well as the implementation of multidisciplinary work should be priorities.
31501866 Haematological abnormalities in new-onset rheumatoid arthritis and risk of common infectio 2020 May 1 OBJECTIVES: To describe the prevalence of haematological abnormalities in individuals with RA at the point of diagnosis in primary care and the associations between haematological abnormalities, vaccinations and subsequent risk of common infections. METHODS: We studied 6591 individuals with newly diagnosed RA between 2004 and 2016 inclusive using the UK Royal College of General Practitioners Research and Surveillance Centre primary care database. The prevalence of haematological abnormalities at diagnosis (anaemia, neutropenia and lymphopenia) was established. Cox proportional hazards models were used to evaluate the association between each haematological abnormality and time to common infections and the influence of vaccination status (influenza and pneumococcal vaccine) on time to common infections in individuals with RA compared with a matched cohort of individuals without RA. RESULTS: Anaemia was common at RA diagnosis (16.1% of individuals), with neutropenia (0.6%) and lymphopenia (1.4%) less so. Lymphopenia and anaemia were associated with increased infection risk [hazard ratio (HR) 1.18 (95% CI 1.08, 1.29) and HR 1.37 (95% CI 1.08, 1.73), respectively]. There was no evidence of an association between neutropenia and infection risk [HR 0.94 (95% CI 0.60, 1.47)]. Pneumonia was much more common in individuals with early RA compared with controls. Influenza vaccination was associated with reduced risk of influenza-like illness only for individuals with RA [HR 0.58 (95% CI 0.37, 0.90)]. CONCLUSION: At diagnosis, anaemia and lymphopenia, but not neutropenia, increase the risk of common infections in individuals with RA. Our data support the effectiveness of the influenza vaccination in individuals with RA.
31701681 Macrophage migration inhibitory factor promoter polymorphisms are associated with disease 2020 Jan BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine capable of stimulating inflammatory cytokine and matrix metalloproteinase production from macrophages and synovial fibroblasts, which leads to persistent inflammation and bone degradation, two of the major pathological processes in rheumatoid arthritis (RA). The aim of this study was to evaluate the association of MIF promoter polymorphisms (-794CATT(5-8) rs5844572 and -173G > C, rs755622), circulating MIF levels, and mRNA expression with RA susceptibility and disease activity. METHODS: A case-control study was conducted in 200 RA patients and 200 control subjects (CS) from Southern Mexico. Genotyping was performed by conventional PCR and PCR-RFLP methods. MIF mRNA expression was quantified by real-time PCR and MIF serum levels were determined by an ELISA kit. RESULTS: The 7,7 (-794CATT(5-8) ) and -173CC (-173G > C) genotypes were associated with higher disease activity in RA patients. MIF serum levels were increased, and MIF mRNA expression was reduced in RA patients as compared to CS. In addition, RA patients with moderate disease activity had higher MIF levels than those with low disease activity. The -794CATT(5-8) and -173G > C MIF polymorphisms were not associated with RA susceptibility. CONCLUSION: These results suggest an important role of MIF polymorphisms and MIF serum levels with disease activity in RA.
33164437 [Effect of shikonin on function of rheumatoid arthritis fibroblast like synoviocytes]. 2020 Oct To observe the effect of shikonin on the proliferation, migration, adhesion and invasion of rheumatoid arthritis(RA) fibroblast like synoviocytes induced by tumor necrosis factor-α(TNF-α), and to explore its mechanism of action from aspects of protein kinase B(Akt) and mitogen activated protein kinase(MAPK) signaling pathways. TNF-α(20 ng·mL~(-1)) was used in this experiment to induce human RA fibroblast like synovial cell line(MH7 A). After addition of different concentrations of shikonin(0.025, 0.05, 0.1 pmol·L~(-1)), the proliferation, migration, adhesion and invasion ability of MH7 A cells were detected by MTT test, scratch test, adhesion test, Transwell invasion test, respectively. Protein expression of Akt and MAPK signaling pathway molecules in MH7 A cells was detected by Western blot. The results showed that as compared with the control group, TNF-α could significantly induce the proliferation, migration, adhesion and invasion of MH7 A cells, and increase the phosphorylation level of Akt, JNK, p38 and extracellular regulatory protein kinase(ERK). As compared with the TNF-α group, shikonin had no significant effect on TNF-α-induced proliferation of MH7 A cells after 24 h treatment, and it could reduce the TNF-α-induced proliferation of MH7 A cells in a concentration dependent manner after 48 h treatment. Shikonin also significantly reduced the TNF-α-induced migration, adhesion, invasion and phosphorylation levels of Akt, JNK, p38, ERK in MH7 A cells within 24 h. These results suggested that shikonin could reduce the proliferation, migration, adhesion and invasion ability of MH7 A cells induced by TNF-α, and its mechanism may be related to the down-regulation of Akt and MAPK signaling pathway activation.
32332732 Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis 2020 Apr 24 Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function.
33082382 Validation of galectin-1 as potential diagnostic biomarker of early rheumatoid arthritis. 2020 Oct 20 Galectin 1 (Gal1) is a lectin with a wide cellular expression that functions as a negative regulator of the immune system in several animal models of autoimmune diseases. Identification of patients with rheumatoid arthritis (RA) has improved during the last decade, although there is still a need for biomarkers allowing an early diagnosis. In this regard, it has been recently proposed that Gal1 serum levels are increased in patients with RA compared to the general population. However, this topic is controversial in the literature. In this work, we provide additional information about the potential usefulness of Gal1 serum levels as a biomarker for RA diagnosis. We studied Gal1 serum and synovial fluid levels and clinical parameters in samples from 62 patients with early arthritis belonging to the PEARL study. In addition, 24 healthy donors were studied. We found that both patients fulfilling RA criteria and patients with undifferentiated arthritis showed higher Gal1 levels than healthy donors. Similar findings were observed in synovial fluid, which showed even higher levels than serum. However, we did not find correlation between Gal1 levels and disease activity or disability. Therefore, our results suggest that Gal1 could be a diagnostic but not a severity biomarker.
31701537 Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthriti 2020 Apr Upadacitinib (ABT-494) is a selective Janus kinase (JAK)1 inhibitor being developed for treatment of several inflammatory disorders. A population pharmacokinetic model was developed for upadacitinib using 11,658 plasma concentrations from 1145 subjects from 4 phase 1 and 5 phase 2 studies in healthy subjects and subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, or atopic dermatitis. A 2-compartment model with first-order absorption and lag time for the immediate-release formulation and mixed zero- and first-order absorption with lag time for the extended-release formulation, and linear elimination adequately described upadacitinib plasma concentration-time profiles. The oral bioavailability of upadacitinib extended-release formulation was estimated to be approximately 80% relative to the immediate-release formulation. Covariates included in the final model were creatinine clearance, subject population (healthy subjects vs subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease vs subjects with rheumatoid arthritis) and sex on apparent oral clearance and sex and body weight on apparent volume of distribution of the central compartment. Female subjects had 21% higher upadacitinib steady-state area under the plasma concentration-time curve (AUC) compared to male subjects. Compared to healthy subjects, subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease had 21% higher upadacitinib steady-state AUC, while subjects with rheumatoid arthritis had 35% higher steady-state AUC. Subjects with mild or moderate renal impairment were estimated to have 10% or 22% higher AUC, respectively, compared to subjects with normal renal function. Based on final model parameter estimates, effects of the tested covariates are not expected to result in clinically relevant changes in upadacitinib steady-state exposures.
31713730 Diagnostic test accuracy of magnetic resonance imaging and ultrasound for detecting bone e 2020 Apr OBJECTIVE: To evaluate and compare the diagnostic test accuracy of magnetic resonance imaging (MRI) and ultrasound (US) for bone erosion in rheumatoid arthritis (RA) patients for a specific and efficient diagnostic recommendation. METHOD: To evaluate the diagnostic accuracy, the sensitivity, specificity, area under the summary receiver operating characteristic curve, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of MRI and US for detecting bone erosion were calculated. Subgroup analyses were conducted to evaluate the performance of these values with different standard references when compared with types of machines and scanning positions. RESULTS: Data from 26 articles were extracted for calculation. The comprehensive values of sensitivity and specificity were 0.77 (95% CI 0.63, 0.87)/0.89 (95% CI 0.80, 0.95) and 0.61 (95% CI 0.43, 0.77)/0.95 (95% CI 0.88, 0.98) for MRI and US, respectively. The 1.5-T Signa MRI system, General Electric© (sensitivity 0.66; specificity 0.90), and different models of LOGIQ US units and General Electric© (sensitivity 0.66; specificity 0.91) had better diagnostic capability to detect bone erosion, while the 2nd metacarpophalangeal joint (sensitivity 0.70; specificity 0.98) showed the best diagnostic performance among the hand joints with US. CONCLUSIONS: Neither MRI nor US showed satisfactory diagnostic test accuracy in detecting bone erosion. However, the 1.5-T Signa MRI system, General Electric©, and different models of LOGIQ US units and General Electric© showed similarly good performance in detecting bone erosion in RA patients, while the 2nd metacarpophalangeal joint is the best recommended scanning position during US. KEY POINTS: • In this study, we evaluated the diagnostic accuracy of US and MRI for bone erosion in RA patients, neither MRI nor US showed perfect diagnostic test accuracy.• 1.5-T Signa system and the LOGIQ units both from General Electric© are the machine types of MRI and US with the greatest performance, respectively.• The 2nd MCP joint is the scanning position recommended during US test.• Different reference standards will greatly influence the judgment of the results.
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.
32586377 Regulation of autoimmune arthritis by the SHP-1 tyrosine phosphatase. 2020 Jun 26 BACKGROUND: The Src homology region 2 domain-containing phosphatase-1 (SHP-1) is known to exert negative regulatory effects on immune cell signaling. Mice with mutations in the Shp1 gene develop inflammatory skin disease and autoimmunity, but no arthritis. We sought to explore the role of SHP-1 in arthritis using an autoimmune mouse model of rheumatoid arthritis. We generated Shp1 transgenic (Shp1-Tg) mice to study the impact of SHP-1 overexpression on arthritis susceptibility and adaptive immune responses. METHODS: SHP-1 gene and protein expression as well as tyrosine phosphatase activity were evaluated in spleen cells of transgenic and wild type (WT) mice. WT and Shp1-Tg (homozygous or heterozygous for the transgene) mice were immunized with human cartilage proteoglycan (PG) in adjuvant, and arthritis symptoms were monitored. Protein tyrosine phosphorylation level, net cytokine secretion, and serum anti-human PG antibody titers were measured in immune cells from WT and Shp1-Tg mice. WT mice were treated with regorafenib orally to activate SHP-1 either before PG-induced arthritis (PGIA) symptoms developed (preventive treatment) or starting at an early stage of disease (therapeutic treatment). Data were statistically analyzed and graphs created using GraphPad Prism 8.0.2 software. RESULTS: SHP-1 expression and tyrosine phosphatase activity were elevated in both transgenic lines compared to WT mice. While all WT mice developed arthritis after immunization, none of the homozygous Shp1-Tg mice developed the disease. Heterozygous transgenic mice, which showed intermediate PGIA incidence, were selected for further investigation. We observed differences in interleukin-4 and interleukin-10 production in vitro, but serum anti-PG antibody levels were not different between the genotypes. We also found decreased tyrosine phosphorylation of several proteins of the JAK/STAT pathway in T cells from PG-immunized Shp1-Tg mice. Regorafenib administration to WT mice prevented the development of severe PGIA or reduced disease severity when started after disease onset. CONCLUSIONS: Resistance to arthritis in the presence of SHP-1 overexpression likely results from the impairment of tyrosine phosphorylation (deactivation) of key immune cell signaling proteins in the JAK/STAT pathway, due to the overwhelming tyrosine phosphatase activity of the enzyme in Shp1-Tg mice. Our study is the first to investigate the role of SHP-1 in autoimmune arthritis using animals overexpressing this phosphatase. Pharmacological activation of SHP-1 might be considered as a new approach to the treatment of autoimmune arthritis.
32315811 Citrullination in periodontium is associated with Porphyromonas gingivalis. 2020 Jun OBJECTIVE: To analyse the citrulline level in the periodontium in association with the presence of or antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. DESIGN: Gingival crevicular fluid (GCF), subgingival biofilm and blood serum were sampled from 98 subjects (26 with RA, 72 without RA (NoRA)). GCF was analyzed for the level of citrulline, for interleukin (IL)-1β, IL-17, IL-10 and monocyte-chemoattractant protein (MCP)-1. Microorganisms were identified in subgingival biofilms. Antibodies againstP. gingivalis, and Aggregatibacter actinomycetemcomitans were quantified in serum. RESULTS: GCF citrulline level was the lowest (by trend) in NoRA group without periodontitis. In NoRA, but not in RA an association between GCF citrulline level and P. gingivalis antibody levels was found and the GCF citrulline levels were higher in P. gingivalis positive samples. Any association of A. actinomycetemcomitans with GCF citrulline level did not exist. A model of univariate variance analysis (p = 0.001) showed a dependence of GCF citrulline level from the number of sites with PD (probing depth) ≥5 mm (p = 0.003) and the GCF MCP-1/CCL2 level (p = 0.019). Compared with NoRA in RA the number of teeth was lower, the number of sites with PD ≥ 5 mm was less, GCF levels of interleukin-17 and MCP-1/CCL2 were higher and those of IL-10 lower. Yeasts were only cultured in 15 RA patients (p < 0.001). CONCLUSION: Citrullination in periodontium might be associated with P. gingivalis supporting the potential role as a trigger in the development of RA. Pathogenesis of periodontal disease in RA patients seems to differ from that in NoRA and should be investigated further.
32141952 Inhalants other than personal cigarette smoking and risk for developing rheumatoid arthrit 2020 May PURPOSE OF REVIEW: The current review summarizes the current evidence on inhalants other than personal cigarette smoking and risk for developing rheumatoid arthritis (RA). RECENT FINDINGS: Personal cigarette smoking has been implicated as an environmental risk factor for seropositive RA, perhaps by inducing autoimmunity at pulmonary mucosa. Since many patients with RA are nonsmokers, other inhalants are being investigated as potential RA risk factors. Recent case-control and cohort studies have investigated passive cigarette smoking, air pollution, inhalant-related occupations, silica, pesticides, household environment, and allergic inhalants as inhalant exposures for RA risk. Inhalant-related occupations and silica inhalants have the most consistent evidence for associations with increased RA risk. However, most studies relied on retrospective designs and had limited ability to adjust for personal cigarette smoking or investigate associations among nonsmokers. SUMMARY: Several inhalants other than personal cigarette smoking may be associated with increased risk for developing RA. These results support the hypothesis that inhalants, pulmonary mucosal inflammation, and RA pathogenesis may be linked. Future studies are needed to firmly establish the independence of these findings from personal cigarette smoking and to determine the specific inhalants and biologic mechanisms related to RA pathogenesis.
31977641 An Estimation Model for Cardiorespiratory Fitness in Adults with Rheumatoid Arthritis. 2020 Jun PURPOSE: Cardiopulmonary exercise testing of peak oxygen uptake (V˙O2peak) is the gold standard to measure cardiorespiratory fitness (CRF). For resource-intensive evaluation, equations estimating CRF (eCRF) may be used. The purpose was to investigate if an eCRF equation from a healthy population is useful in persons with rheumatoid arthritis (RA), and if necessary, develop new equations for eCRF in this group. METHODS: V˙O2peak results from 93 persons with RA were compared with eCRF calculated by an established equation for healthy individuals including age, sex, physical activity (PA index), resting HR (RHR), and waist circumference. Because of deviation from the observed V˙O2peak, new equations for eCRF in persons with RA were developed from regression analysis of variables associated with observed V˙O2peak. RESULTS: The established equation overestimated CRF (R = 0.48, root mean square error [RMSE] = 7.07). The new RA equation more accurately estimated CRF (R = 0.81, RMSE = 4.44) (female = 0, male = 1; never smoked = 0, ever smoked = 1): eCRF = 77.961 + (sex × 28.791) - (age × 0.358) - (age-sex interaction × 0.326) - (body mass index [BMI] × 0.700) - (RHR × 0.125) - (smoking × 1.854) + (PA index × 0.211) - (patient global RA assessment × 0.071). Alternative new RA equation (R = 0.79, RMSE = 4.63): eCRF = 77.851 + (sex × 25.460) - (age × 0.381) - (age-sex interaction × 0.254) - (BMI × 0.743) - (RHR × 0.115) - (smoking × 2.154) + (PA index × 0.209). CONCLUSIONS: The new RA equations better predicted CRF in individuals with RA, preventing overestimation in low-fit persons. The new equation should be preferred when estimating CRF in individuals with RA. The alternative equation, without patient global assessment, is useful for individuals with RA in population-based studies.
32478946 The association between serum levels of growth differentiation factor-15 and rheumatoid ar 2020 Sep BACKGROUND: Macrophages play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Growth differentiation factor-15 (GDF-15) acts as an autocrine regulator of macrophage activation. OBJECTIVE: The aim of this study was to assess serum level of GDF-15 as a potential biomarker for detecting RA activity. METHOD: A total of 100 female RA patients and 55 age and weight matched healthy control females were enroled. The serum level of GDF-15 was measured using enzyme-linked immunosorbent assay. RESULTS: Serum levels of GDF-15 in RA patients with high, moderate, low and no disease activity were 989.0 ± 161.9, 505.6 ± 220.5, 349.2 ± 155.9 and 349.0 ± 144.0 pg/mL, respectively. GDF-15 with a cut-off value higher than 705 pg/mL was indicative of high RA activity with sensitivity of 96% and specificity of 92%. CONCLUSION: GDF-15 serum levels may be used as a biomarker to predict high RA disease activity.
32292017 Association between red cell distribution width and response to methotrexate in rheumatoid 2020 Apr 10 Red cell distribution width (RDW) is an unconventional biomarker of inflammation. We aimed to explore its role as a predictor of treatment response in rheumatoid arthritis (RA). Eighty-two RA patients (55 females), median age [interquartile range] 63 years [52-69], were selected by scanning the medical records of a rheumatology clinic, to analyze the associations between baseline RDW, disease activity scores and inflammatory markers, as well as the relationship between RDW changes following methotrexate (MTX) and treatment response. The lower the median baseline RDW, the greater were the chances of a positive EULAR response at three months, 13.5% [13.0-14.4] being among those with good response, vs 14.0% [13.2-14.7] and 14.2% [13.5- 16.0] (p=0.009) among those with moderate and poor response, respectively. MTX treatment was followed by a significant RDW increase (p<0.0001). The increase of RDW was greater among patients with good EULAR response, becoming progressively smaller in cases with moderate and poor response (1.0% [0.4-1.4] vs. 0.7 [0.1-2.0] vs. 0.3 [-0.1-0.8]; p=0.03). RDW is a strong predictor of early response to MTX in RA. RDW significantly increases after MTX initiation in parallel to treatment response, suggesting a role as a marker of MTX effectiveness.
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.