Browse

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

ID PMID Title PublicationDate abstract
31994996 Abatacept reduces disease activity of rheumatoid arthritis independently of modulating ant 2020 Jun Abatacept may exert its clinical effect on rheumatoid arthritis (RA) by suppressing anti-cyclic citrullinated peptide (CCP) antibody production. This study was undertaken to test this hypothesis by examining the changes of disease activity of RA and anti-CCP antibody levels over time after starting abatacept. Sixty Japanese RA patients who started abatacept were included in this multicenter, prospective observational study. Simple Disease Activity Index (SDAI) and anti-CCP antibody levels were evaluated at 12, 24, and 52 weeks. The mean SDAI score significantly decreased within 12 weeks after starting abatacept and was maintained thereafter. On the contrary, the mean anti-CCP antibody levels did not change until 52 weeks. At the individual level, there were substantial changes of anti-CCP antibody levels, but these were not correlated with the changes of disease activity at any time points. Thus, abatacept reduces the disease activity of RA independently of modulating anti-CCP antibody production.
31701185 Periodontal disease and influence of periodontal treatment on disease activity in patients 2020 Mar The aim of this study was to assess the prevalence of periodontal disease and the effect of periodontal treatment in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Forty-four RA patients, thirty SpA patients and thirty-nine healthy volunteers were recruited to the study. Periodontal examination included the approximal plaque index (API), bleeding on probing (BoP), probing depth (PD) and number of teeth. Samples from the deepest periodontal pockets were taken for the detection of Porphyromonas gingivalis DNA with the use of the polymerase chain reaction. All subjects with periodontitis, who completed the study, received periodontal treatment consisting of scaling/root planing and oral hygiene instructions. Disease activity scores, clinical and laboratory parameters were assessed before and 4-6 weeks after periodontal treatment. No significant difference in the prevalence of periodontal disease and the presence of P. gingivalis DNA were found in RA and SpA patients compared to healthy controls. Significantly higher API (80% vs 63%; p = 0.01) and a lower number of teeth (20 vs 25, p = 0.001) were found in RA patients. BoP was significantly elevated in SpA patients (51% vs 33%, p = 0.02). Disease activity measured by the DAS28(CRP) was significantly reduced in RA patients after periodontal treatment (p = 0.002). Clinical and biochemical parameters were not improved in SpA patients. Nonsurgical periodontal treatment had an impact on the decrease in RA activity. Periodontal examination is necessary in patients with RA to detect and treat periodontitis at an early stage.
31140396 CD74 is a T cell antigen in spondyloarthritis. 2020 Mar OBJECTIVES: Spondyloarthritis (SpA) is a chronic inflammatory disease of unknown aetiology. Previously, we identified autoantibodies against CD74 in sera of SpA patients. The aim of this study was to evaluate CD74 as a T cell antigen in SpA. METHODS: Recombinant CD74 protein and a panel of selected peptides representing its amino acid residues were examined for their capability to stimulate peripheral blood mononuclear cells from patients with SpA. In particular, cytokine production by CD4+ T cells was evaluated with flow cytometric detection of intracellular TNF-α, IFNγ, TGFβ and IL-17A. Patients' sera were tested for antibodies against CD74 using ELISA. Samples from patients with rheumatoid arthritis and healthy blood donors were similarly tested as controls. RESULTS: Significantly more CD4+ T cells from SpA patients produced TNF-α, IFNγ and IL-17A in response to recombinant CD74 than patients with rheumatoid arthritis or healthy blood donors. Among evaluated epitopes, the most promiscuous one lies within the peptide of the amino acid residues 142-185, which appeared more immunogenic. Further, the proportion of cytokine producing CD4+ T cells was significantly higher among SpA patients with autoantibodies against CD74. CONCLUSIONS: CD74 is a T cell antigen in SpA, eliciting Th1 and Th17 responses, which may be relevant in disease pathogenesis. Recognition of the highly immunogenic amino acid residues of CD74 may contribute to our understanding of autoimmune responses of T helper cells in SpA.
32970187 [Autoantibodies and the autoreactive immune response : There is more to ACPA than ACPA]. 2020 Nov The immune response against posttranslationally modified (PTM) antigens, in particular the generation of anti-citrullinated protein antibodies (ACPA), is a very specific hallmark of rheumatoid arthritis. The factors that initiate this immune response and the triggers that stimulate the transition from asymptomatic autoimmunity to autoimmune disease are so far unknown. Genetic risk factors and the maturation of the ACPA response prior to the onset of arthritis indicate an important role for helper T cells in this process. Antigens that trigger this process, however, remain to be defined. Notably, recent data demonstrate that ACPA do not only recognize citrullinated protein antigens. Other posttranslational protein modifications such as homocitrulline and acetyllysine are also recognized. This cross-reactivity towards different PTM antigens was found for various monoclonal ACPA and broadens the spectrum of antigens that can stimulate and activate ACPA-expressing B cells. Also, it suggests that such B cells could receive help from autoreactive but also from non-autoreactive T cells. This review summarizes these recent findings and provides insight into their potential relevance for the disease rheumatoid arthritis.
32514765 Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receivi 2020 Nov In this population-based cohort study on comparative osteoporotic fracture risks between different biologic disease-modifying drugs among patients with rheumatoid arthritis (RA), we did not find a significant difference in the risk of osteoporotic fractures between RA patients receiving TNF inhibitors versus abatacept or tocilizumab. INTRODUCTION: We aimed to investigate the comparative risk of osteoporotic fractures between rheumatoid arthritis (RA) patients who initiated TNF inhibitors (TNFis) versus abatacept or tocilizumab. METHODS: Using the Korea National Health Insurance Service datasets from 2002 to 2016, RA patients who initiated TNFis, abatacept, or tocilizumab were identified. The primary outcome was a composite end point of non-vertebral fractures and hospitalized vertebral fractures; secondary outcomes were two components of the primary outcome and fractures occurring at the humerus/forearm. Propensity score (PS) matching with a variable ratio up to 10 TNFi initiators per 1 comparator drug initiator was used to adjust for > 50 baseline confounders. We estimated hazard ratios (HRs) and 95% confidence interval (CI) of fractures comparing TNFi initiators to abatacept and to tocilizumab by Cox proportional hazard models stratified by a matching ratio. RESULTS: After PS-matching, 2307 TNFi initiators PS-matched on 588 abatacept initiators, and 2462 TNFi initiators on 640 tocilizumab initiators were included. A total of 77 fractures occurred during a mean follow-up of 454 days among TNFi and abatacept initiators and 83 fractures during 461 days among TNFi and tocilizumab initiators. The PS-matched HR (95% CI) was 0.91 (0.48-1.71) comparing TNFi versus abatacept initiators, and 1.00 (0.55-1.83) comparing TNFi versus tocilizumab initiators. Analysis on vertebral and non-vertebral fractures showed similar results. CONCLUSIONS: In this nationally representative cohort, we did not find a significant difference in the risk of fractures between TNFi initiators versus abatacept or tocilizumab among RA patients.
32054521 Association between periodontitis and anti-citrullinated protein antibodies in rheumatoid 2020 Feb 13 AIM: The aim of this study was to evaluate the association between periodontal parameters related with the periodontal disease severity and the presence and levels of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: This cross-sectional study included 164 RA patients. Socio-demographics and RA disease characteristics, including ELISA-detected ACPA (anti-CCP-2), were recorded. Exposure was assessed by periodontal parameters: plaque index (PI), bleeding on probing (BoP), probing pocket depth, and clinical attachment levels (CAL). Presence and levels of ACPAs (outcome) and exposure variables were compared by both parametric and non-parametric tests and associations were evaluated by adjusted odds ratio (OR). RESULTS: A significant association was observed between the presence of anti-CCP antibodies and severity of periodontal outcomes such as the mean CAL (OR 1.483, p = 0.036), mean PI (OR 1.029, p = 0.012), and the number of pockets ≥ 5 mm (OR 1.021, p = 0.08). High anti-CCP antibodies levels were associated with mean CAL, mean PI, and number of pockets ≥ 5 mm with an OR of 1.593 (p = 0.043), 1.060 (p <  0.001), and 1.031 (p = 0.031), respectively. Furthermore, a significant increase of 4.45 U/mL in anti-CCP antibodies levels (p = 0.002) in RA patients was found for each pocket ≥ 5 mm after adjusting for age, gender, smoking, time of disease evolution, and RA activity. CONCLUSIONS: In RA patients, the severity of periodontal conditions such as mean CAL, mean PI, and the number of pockets ≥ 5 mm were linearly associated with both the presence and levels of anti-CCP antibodies.
31116126 Clinical Effectiveness and Safety of Treatment With Anti-Tumor Necrosis Factor α Drugs in 2020 Oct OBJECTIVE: To compare the clinical response at 24 months and evaluate the adverse events (AEs) of patients with rheumatoid arthritis (RA) treated with etanercept 50 (injectable solution 50 mg prefilled syringe), etanercept 25 (lyophilized 25 mg), infliximab, adalimumab, or golimumab. METHODS: A cohort study was carried out in patients with RA, in treatment with etanercept (injectable solution 50 mg prefilled syringe or lyophilized 25 mg), infliximab, adalimumab, or golimumab. Duration of study: follow-up was carried out for 24 months. The difference of initial and final 28-joint Disease Activity Score, remission incidence, difference of initial and final Health Assessment Questionnaire score, disability recovery, and AE rate were evaluated. RESULTS: The study enrolled 435 patients (108 adalimumab, 107 infliximab, 92 etanercept 25 mg, 81 etanercept 50 mg, and 47 golimumab). For etanercept 50, the median difference between basal and at the end of follow-up 28-joint Disease Activity Score was 1.7. For golimumab, it was 1.4; for adalimumab, it was 1.1; for etanercept 25, it was 1.02; and for infliximab, it was 0.96 (p = 0.001). The median difference between basal and final Health Assessment Questionnaire ranged was 1.66 for etanercept 50, 1.34 for etanercept 25, 1.3 for golimumab, 1.24 for adalimumab, and 1.07 for infliximab (p = 0.0005). Comparatively, etanercept 50 presented the highest cumulative incidence (77%; 95% confidence interval [CI], 67%-86%) and remission incidence (64 cases per 100 person-months; 95% CI, 4.9-8.1 cases per 100 person-months) and the lowest AE rate (8.6 per 100 person-years; 95% CI, 5.3-15 per 100 person-years). CONCLUSIONS: In patients with RA treated with anti-tumor necrosis factor α drugs, the highest incidence of remission and the lowest rate of AEs were documented for the cohort exposed to etanercept 50 mg.
31792368 Genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate 2020 Jun The objective of the study is to develop genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Among RA patients treated with MTX, 1966 polymorphisms of 246 enzymes/transporters relevant to pharmacokinetics and pharmacodynamics were measured by the Drug Metabolism Enzymes and Transporters (DMET) microarray and direct sequencing, and clinical variables at baseline were collected. For efficacy, response criteria of the European League Against Rheumatism were used to classify patients as responders or non-responders. Hepatotoxicity was defined as elevations of aspartate aminotransferase or alanine aminotransferase ≥1.5 times the reference range upper limit. Among 166 patients, a genetic prediction model for efficacy using seven polymorphisms showed the area under the receiver operating characteristic curve (AUC) was 0.822, with 74.3% sensitivity and 76.8% specificity. A combined genetic and clinical model indicated the AUC was 0.844, with 81.5% sensitivity and 76.9% specificity. By incorporating clinical variables into the genetic model, the overall category-free net reclassification improvement (NRI) was 0.663 (P < 0.0001) and the overall integrated discrimination improvement (IDI) was 0.083 (P = 0.0009). For hepatotoxicity, a genetic prediction model using seven polymorphisms showed the AUC was 0.783 with 70.0% sensitivity and 80.0% specificity, while the combined model indicated the AUC was 0.906 with 85.1% sensitivity and 87.8% specificity (overall category-free NRI: 1.002, P < 0.0001; overall IDI: 0.254, P < 0.0001). Our genetic and clinical models demonstrated moderate diagnostic accuracy for MTX efficacy and high accuracy for hepatotoxicity. These findings should, however, be validated and interpreted with a caution until external validation.
32678069 MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheuma 2020 Jul 17 Fibroblast-like synoviocytes (FLSs) are key effector cells in the pathogenesis of rheumatoid arthritis (RA) and display a unique aggressive tumor-like phenotype with remarkable hyperplasia, increased cell migration and invasion. How FLSs undergo these changes in RA remains unknown. We previously reported a novel function of transcription factor SOX5 in RA-FLSs that promote cell migration and invasion. In this study, we found that miR-15a/16 directly targets the SOX5 3'UTR and suppresses SOX5 expression. Moreover, miR-15a/16 is significantly down-regulated in RA-FLSs, which negatively correlates with SOX5 expression. Transfection with miR-15a/16 mimics in RA-FLSs inhibits cell migration, invasion, IL-1β and TNFα expression. Overexpression SOX5 in RA-FLSs decreases miR-15a/16 expression and rescues miR-15a/16-mediated inhibitory effect. Furthermore, RA patients with the lower baseline serum miR-15a/16 level present poor response of 3 months disease-modifying antirheumatic drugs (DMARDs) therapy. Collectively, this study reveals that miR-15a/16/SOX5 axis functions as a key driver of RA-FLSs invasion, migration and inflammatory response in a mutual negative feedback loop and correlates with DMARDs treatment response in RA.
32907614 The multi-biomarker disease activity test for assessing response to treatment strategies u 2020 Sep 9 OBJECTIVES: The CAMERA-II trial compared two tight-control, treat-to-target strategies, initiating methotrexate with prednisone (MTX+pred) or MTX with placebo (MTX+plac), in early RA-patients. The multi-biomarker disease activity (MBDA) blood test objectively measures RA disease activity with a score of 1-100. In CAMERA-II, response profiles of the MBDA score, its individual biomarkers, and DAS28 were assessed. METHODS: We evaluated 92 patients from CAMERA-II of whom clinical data and serum for MBDA testing at baseline and ≥ 1 time-point from months 1, 2, 3, 4, 5, 6, 9, or 12 were available. Changes (∆) from baseline for DAS28 and MBDA score and comparisons of ∆DAS28 and ∆MBDA score over time within the MTX+pred versus the MTX+plac strategy were tested for significance with t tests. Changes in biomarker concentration from baseline to months 1-5 were tested with Wilcoxon signed rank test and tested for difference between treatment arms by Mann-Whitney U test. RESULTS: MBDA and DAS28 showed similar response profiles, with gradual improvement over the first 6 months in the MTX+plac group, and in the MTX+pred group faster improvement during month 1, followed by gradual improvement. The 12 MBDA biomarkers could be grouped into 4 categories of response profiles, with significant responses for 4 biomarkers during the MTX+plac strategy and 9 biomarkers during the MTX+pred strategy. CONCLUSIONS: MBDA tracked treatment response in CAMERA-II similarly to DAS28. More individual MBDA biomarkers tracked treatment response to MTX+pred than to MTX+plac. Four response profiles could be observed. TRIAL REGISTRATION: CAMERA-II International Standard Randomised Controlled Trial Number: ISRCTN 70365169 . Registered on 29 March 2006, retrospectively registered.
32338225 TLRs Play Crucial Roles in Regulating RA Synoviocyte. 2020 Rheumatoid arthritis (RA) is an autoimmune inflammatory disease comparing the inflammation of synovium. Macrophage-like synoviocytes and fibroblast-like synoviocytes (synoviocytes) are crucial ingredients of synovium. Therein, a lot of research has focused on synoviocytes. Researches demonstrated that TLR1, TLR2, TLR3, TLR4, TLR5, TLR6 TLR7 and TLR9 are expressed in synoviocyte. Additionally, the expression of TLR2, TLR3, TLR4 and TLR5 is increased in RA synoviocyte. In this paper, we review the exact role of TLR2, TLR3, TLR4 and TLR5 participate in regulating the production of inflammatory factors in RA synoviocyte. Furthermore, we discuss the role of vasoactive intestinal peptide (VIP), MicroRNA, Monome of Chinese herb and other cells (Monocyte and T cell) influence the function of synoviocyte by regulating TLRs. The activation of toll-like receptors (TLRs) in synoviocyte leads to the aggravation of arthritis, comparing with angiogenesis and bone destruction. Above all, TLRs are promising targets for managing RA.
32122392 High-resolution MRI of flexor tendon pulleys using a 16-channel hand coil: disease detecti 2020 Mar 2 BACKGROUND: To evaluate the value of 3 Tesla (T) magnetic resonance imaging (MRI) changes of flexor tendon pulleys for the differentiation of psoriatic (PsA) and rheumatoid arthritis (RA), using a novel 16-channel high-resolution hand coil. METHODS: Seventeen patients with active PsA, 20 patients with active RA, and 16 healthy controls (HC) underwent high-resolution 3 T MRI using the dedicated 16-channel hand coil. Images were analyzed by three independent readers for the degree of inflammatory changes, thickness of flexor tendon pulleys, and comparison to the outcome measures for RA clinical trials (OMERACT) PsA MRI score (PsAMRIS) and to its sub-scores. For correlation analyses, Spearman rho correlation was calculated. RESULTS: Flexor tendon pulleys were thicker in PsA than in RA patients (mean difference 0.16 mm, p < 0.001) and HC (mean difference 0.2 mm, p < 0.001) and showed a higher degree of associated inflammatory changes (mean difference from RA 4.7, p = 0.048; mean difference from HC 14.65, p < 0.001). Additionally, there was a strong correlation of accessory pulley inflammation and PsAMRIS and its acute-inflammatory sub-scores, flexor tenosynovitis, synovitis, and periarticular inflammation (for the second digit synovitis ρ = 0.72, flexor tenosynovitis ρ = 0.7, overall PsAMRIS ρ = 0.72, p < 0.01). Similar robust correlations were evident in digits 3-5. Weaker correlations were evident in RA (synovitis ρ = 0.49, flexor tenosynovitis ρ = 0.49, periarticular inflammation ρ = 0.4). CONCLUSION: The assessment of MRI changes of flexor tendon pulleys is potentially beneficial for disease detection in PsA, as well as for its distinction from RA and HC. TRIAL REGISTRATION: 2014123117, December 2014.
32573409 Toenail abnormalities in rheumatoid arthritis patients are associated with radiographic da 2021 May OBJECTIVES: Cutaneous involvement is an extra-articular manifestation of rheumatoid arthritis (RA). This includes nail abnormalities, which are often overlooked. We described nail findings in RA patients currently attending an early arthritis cohort (n=145), and associated them with disease activity and/or damage, as well as patient-reported outcomes. METHODS: A standardised nail examination was performed in 122 patients (84.1% of the cohort), concomitant to the rheumatic assessment. Disability, quality of life and perceived nail-related health were also assessed. Nail findings and their location were recorded and classified according to standardised definitions. Logistic and linear regression models were used to investigate predictors of nail findings and to identify the impact of toenail findings on disability, which was evaluated with the HAQ. Patients consented to participate. RESULTS: Patients were primarily middle-aged females, with median follow-up of 9 years, and had disease under control. Most patients (62.3%) had at least one nail finding and these patients scored lower their nail-related health. The median (IQR) of findings/abnormalities per patient was 3 (2-5) and the number of nails affected per patient was 10 (2-12). Age (OR: 1.04, 95%CI: 1.007-1.074) and erosive disease (OR: 2.26, 95%CI: 1.1-5.1) were associated with nail findings. Toenail involvement was consistently associated with HAQ score out of normal range (OR=3.4, 95%CI=1.24-9.35, p=0.02). There was a linear association between the number of toenails affected and the HAQ score. CONCLUSIONS: Nail abnormalities are common and heterogeneous findings in RA patients; they are associated with erosive damage and impact disability.
33126340 T cell immunoglobulin and mucin domain-3 is associated with disease activity and progressi 2020 Oct 30 T cell immunoglobulin and mucin domain-3 (TIM-3) is a surface molecule expressed on immune cells which play a role in immune regulation. The aims of the present study were to determine whether circulating soluble T cell immunoglobulin domain and mucin-3 (sTIM-3) are elevated in rheumatoid arthritis (RA) patients, and investigate the relationships between sTIM-3 and clinical features of RA.The study included 116 patients with established RA and 27 healthy control subjects. Serum levels of sTIM-3 were measured via the enzyme-linked immunosorbent assays (ELISA). Correlations between serum sTIM-3 and a range of parameters including anti-citrullinated peptide antibody (ACPA) titer, erythrocyte sedimentation rate (ESR), and matrix metalloproteinase-3 (MMP-3) were assessed.Serum sTIM-3 was significantly elevated in RA patients compared with those in healthy subjects, and it was positively correlated with ACPA titer (r = 0.27 P = .005), ESR (r = 0.27, P = .004) and MMP-3 (r = 0.35, P < .001). In RA patients with high ACPA titers (≥200 U/mL), sTIM-3 was not correlated with ESR or MMP-3. Whereas, sTIM-3 was significantly correlated with ESR and MMP-3 in RA patients with low ACPA titers (<200 U/mL).Serum sTIM-3 was increased in RA patients, and it was associated with proinflammatory markers and disease activity in RA patients under a particular ACPA status. Our data suggest that circulating sTIM-3 may be a useful biomarker for the determination of disease activity in RA patients.
33202579 Diet as a Modulator of Intestinal Microbiota in Rheumatoid Arthritis. 2020 Nov 14 Rheumatoid arthritis (RA) is a chronic immune-driven inflammatory disease characterised by synovial inflammation, leading to progressive cartilage and bone destruction, impacting patients' functional capacity and quality of life. Patients with RA have significant differences in gut microbiota composition when compared to controls. Intestinal dysbiosis influences the intestinal barrier strength, integrity and function, and diet is considered the main environmental factor impacting gut microbiota. Over the last few years, researchers have focused on the influence of single components of the diet in the modulation of intestinal microbiota in RA rather than whole dietary patterns. In this review, we focus on how the Mediterranean diet (MD), a whole dietary pattern, could possibly act as an adjuvant therapeutic approach, modulating intestinal microbiota and intestinal barrier function in order to improve RA-related outcomes. We also review the potential effects of particular components of the MD, such as n-3 polyunsaturated fatty acids (PUFAs), polyphenols and fibre.
33004335 EULAR definition of difficult-to-treat rheumatoid arthritis. 2021 Jan BACKGROUND: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking. OBJECTIVE: The Task Force in charge of the "Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step. METHODS: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). RESULTS: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. CONCLUSIONS: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.
32849620 Intestinal Dysbiosis and Tryptophan Metabolism in Autoimmunity. 2020 The development of autoimmunity involves complex interactions between genetics and environmental triggers. The gut microbiota is an important environmental constituent that can heavily influence both local and systemic immune reactivity through distinct mechanisms. It is therefore a relevant environmental trigger or amplifier to consider in autoimmunity. This review will examine recent evidence for an association between intestinal dysbiosis and autoimmune diseases, and the mechanisms by which the gut microbiota may contribute to autoimmune activation. We will specifically focus on recent studies connecting tryptophan metabolism to autoimmune disease pathogenesis and discuss evidence for a microbial origin. This will be discussed in the context of our current understanding of how tryptophan metabolites regulate immune responses, and how it may, or may not, be applicable to autoimmunity.
31557754 Coping and Life Satisfaction: Mediating Role of Ego-Resiliency in Patients with Rheumatoid 2020 OBJECTIVE: Ego-resiliency is attributed the status of a "meta resource" that is responsible for a flexible selection of coping strategies depending on the requirements of a specific difficult situation. A considerably burdensome critical life event is the development of a chronic illness such as rheumatoid arthritis (RA). Apart from coping with the symptoms, a fundamental task confronting patients is maintaining their quality of life. This raises the question of whether ego-resiliency serves as a mediator between coping strategies and quality of life. MATERIALS AND METHODS: 210 RA patients were invited to participate in this study. They were requested to complete a questionnaire that included the Satisfaction with Life scale, the stress coping inventory Mini-COPE, and the Ego-Resiliency scale. The collected data were analyzed by a simple mediation procedure and estimation of simple correlation coefficients. RESULTS: The analysis demonstrated that ego-resiliency (r = 0.46; p < 0.001) and emotion-focused coping (r = 0.39; p < 0.001) determined life satisfaction. Additionally, ego-resiliency mediated the relation between emotion-oriented coping strategies and life satisfaction. Partial mediation was observed (a = 0.45**; b = 0.36**; c = 0.39**; c' =0.22**; R2 = 0.24; F = 35.65; p < 0.001). CONCLUSION: Our observations partly support the assumption about a controlling role of ego-resiliency in the process of selecting coping strategies according to demands of situations.
33210410 Biomarkers and immunological parameters in haemophilia and rheumatoid arthritis patients: 2021 Jan INTRODUCTION: Haemophilia (HA) and rheumatoid arthritis (RA) patients may develop joint damage caused by recurrent joint bleedings in HA or by chronic inflammation in RA. Only few data exist for biomarker studies in these patients. AIM: The objective of the present study is to assess a large array of biomarkers in peripheral blood samples obtained from HA patients without or with arthropathy and to compare pattern to RA patients and healthy controls. METHODS: A panel of biomarkers was assessed in 129 men (40 HA patients without arthropathy, 23 HA patients with arthropathy, 23 RA patients and 43 control subjects). 37 different biomarkers (cytokines, angiogenesis-related proteins) were analysed using a multiple analyte profiling technology and supplemented by acute phase proteins, coagulation and immunological parameters. RESULTS: Evidence for systemic inflammation was obtained by increased acute phase reactants in all patient groups. 13 or 14 from 42 soluble parameters demonstrated significant differences (p < .05) between HA patients without arthropathy and healthy controls, or between HA patients with arthropathy and healthy controls, respectively. Largely overlapping patterns were obtained except for interleukin-7 being increased in HA patients without arthropathy and being decreased in HA in the presence of arthropathy. CONCLUSIONS: In addition to data supporting systemic inflammation, we provide evidence for a common biomarker profile in HA patients and RA patients compared to healthy controls. A distinctive biomarker profile for HA patients with arthropathy did not appear except for interleukin-7 demonstrating specific changes depending on the absence or presence of arthropathy in HA patients.
33385862 C-reactive protein and implications in rheumatoid arthritis and associated comorbidities. 2021 Feb C-reactive protein (CRP) is routinely assessed as a marker of systemic inflammation in rheumatoid arthritis (RA). However, it is also an immune regulator that plays an important role in inflammatory pathways associated with RA and promotes atherogenic effects. Comorbidities linked to systemic inflammation are common in RA, and CRP has been associated with the risk for cardiovascular disease, diabetes, metabolic syndrome, pulmonary diseases, and depression. The relationship between systemic inflammation, CRP, and comorbidities in RA is complex, and it is challenging to determine how changing CRP levels may affect the risk or progression of these comorbidities. We review the biological role of CRP in RA and its implications for disease activity and treatment response. We also discuss the impact of treatment on CRP levels and whether reducing systemic inflammation and inhibiting CRP-mediated inflammatory pathways may have an impact on conditions commonly comorbid with RA.