Browse

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

ID PMID Title PublicationDate abstract
31674683 Pain appraisal and quality of life in 108 outpatients with rheumatoid arthritis. 2020 Apr Individual differences in emotional functioning, pain appraisal processing, and perceived social support may play a relevant role in the subjective experience of pain. Due to the paucity of data regarding individuals with Rheumatoid Arthritis (RA), the present study aimed to examine pain intensity, emotional functioning (psychological distress and alexithymia), pain appraisal (pain beliefs, pain catastrophizing, and pain-related coping strategies) and social support, and their relationships with the health-related quality of life (HRQoL) in patients with RA. Data were collected from 108 female patients diagnosed with RA. Clinically relevant levels of depressive and anxiety symptoms assessed by the HADS subscales were present in 34% and 41% of the patients, respectively, and about 24% of them exhibited the presence of alexithymia. The results of hierarchical multiple regression analyses showed that pain intensity, alexithymia, the maladaptive beliefs regarding the stability of pain and the coping strategy of guarding explained 54% of the variance in the physical component of HRQoL (p < 0.001). Depression subscale of the HADS, alexithymia, the coping strategy of resting, and the rumination factor of pain catastrophizing significantly explained 40% of the variance in the mental component of HRQoL (p < 0.001). The present findings provide evidence regarding the importance of emotional functioning and pain appraisal in the negative impact of RA on patients' quality of life. These findings provide additional evidence for the biopsychosocial model of chronic pain, further supporting the complex interaction between emotional, cognitive, and behavioral processes in patients with chronic pain.
31147698 Gender differences in cardiovascular risk of patients with rheumatoid arthritis. 2019 Sep 1 BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease, affecting women more than men, with a more aggressive course in women. DESIGN: A prospective study that recruited 58 patients (46 women aged 56 ± 12 years) with active long-standing RA disease (>12 months). Our goals were to measure their endothelial function, part of the cardiovascular risk assessment. METHODS: The Brachial Artery method measured endothelial function (the flow mediated percent change [FMD percentage] of the brachial artery diameter). A senior Rheumatologist clinically evaluated all subjects. Mann Whitney rank sum test estimated gender differences among the RA patients. RESULTS: Median FMD% change for men was -6.07%, while median FMD% change for women was 0.44% (Z = 2.38, P = 0.01). Baseline Brachial artery diameter was larger in men (Z = 2.52, P = 0.01); however, tender joints count and BMI were greater in women (Z=-2.24, P = 0.01; Z=-3.99, P = 0.001), respectively. CONCLUSIONS: Women with RA have significantly better endothelial function than men with RA. It means that even though RA is 3-fold more prevalent in women, women are more protected from atherosclerotic coronary artery disease and cardiac events.
31647025 Molecular profiling of rheumatoid arthritis patients reveals an association between innate 2019 Oct 23 BACKGROUND: The goal of this study is to use comprehensive molecular profiling to characterize clinical response to anti-TNF therapy in a real-world setting and identify reproducible markers differentiating good responders and non-responders in rheumatoid arthritis (RA). METHODS: Whole-blood mRNA, plasma proteins, and glycopeptides were measured in two cohorts of biologic-naïve RA patients (n = 40 and n = 36) from the Corrona CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) registry at baseline and after 3 months of anti-TNF treatment. Response to treatment was categorized by EULAR criteria. A cell type-specific data analysis was conducted to evaluate the involvement of the most common immune cell sub-populations. Findings concordant between the two cohorts were further assessed for reproducibility using selected NCBI-GEO datasets and clinical laboratory measurements available in the CERTAIN database. RESULTS: A treatment-related signature suggesting a reduction in neutrophils, independent of the status of response, was indicated by a high level of correlation (ρ = 0.62; p < 0.01) between the two cohorts. A baseline, response signature of increased innate cell types in responders compared to increased adaptive cell types in non-responders was identified in both cohorts. This result was further assessed by applying the cell type-specific analysis to five other publicly available RA datasets. Evaluation of the neutrophil-to-lymphocyte ratio at baseline in the remaining patients (n = 1962) from the CERTAIN database confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03-1.41, p = 0.02]). CONCLUSION: Differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy.
31087698 Geldanamycin induces apoptosis and inhibits inflammation in fibroblast-like synoviocytes i 2019 Sep Rheumatoid arthritis (RA) is an autoimmune disease of the joints characterized by synovial hyperplasia and chronic inflammation. Fibroblasts-like synoviocytes (FLS), major cells in the synovium, together with infiltrated leukocytes, contribute greatly to RA progression. In our study, we hypothesized that geldanamycin (GA), a cancer drug might be able to inhibit RA FLS growth. To test the idea, RA FLS were isolated and cultured for cancer drug test. The results showed that GA can specifically inhibit the growth of RA FLS compared with normal FLS. Essentially, GA was found to promote reactive oxygen species production in RA FLS and induce programmed cell death. The annexinV/propidium iodide and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining confirmed that GA can directly induce apoptosis and subsequently inhibit the growth of RA FLS, which was also confirmed by Western blot assay. In addition, our data demonstrated that inflammation was inhibited by suppressed nuclear factor κB signaling pathway. The therapeutic effect of GA was explored in collagen-induced arthritis mice. In short, GA was a promising drug for the treatment of RA by specifically inhibiting the proliferation and inflammation of RA FLS.
31733368 The Giants (biologicals) against the Pigmies (small molecules), pros and cons of two diffe 2020 Jan Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that, if untreated, can lead to disability and reduce the life expectancy of affected patients. Over the last two decades the improvement of knowledge of the pathogenetic mechanisms leading to the development of the disease has profoundly changed the treatment strategies of RA through the development of biotechnological drugs (bDMARDs) directed towards specific pro-inflammatory targets involved in the RA network. To date, the therapeutic armamentarium for RA includes ten bDMARDs able to produce the depletion B-cells, the blockade of three different pro-inflammatory cytokines (tumour necrosis factor alpha, interleukin-6 and interleukin-1), or the inhibition of T-cell co-stimulation. The introduction of these new compounds has dramatically improved outcomes in the short and long term, although still a significant proportion of patients are unable to reach or maintain the treatment target over time. The identification of the fundamental role of Janus kinases in the process of transduction of the inflammatory signal within the immune cells has recently provided the opportunity to use the new pharmacological class of small molecules for the therapy of RA, further increasing the number of treatment options. In this review the PROS and CONS of these two drug classes will be discussed, trying to provide the evidence currently available to make the right choice based on the analysis of the efficacy and safety profile of the different drugs on the market and close to marketing.
31644963 MAST3 modulates the inflammatory response and proliferation of fibroblast-like synoviocyte 2019 Dec Via promoting synovitis, pannus growth and cartilage/bone destruction, fibroblast-like synovial cells (FLSs) play a significant role in the pathogenesis of rheumatoid arthritis (RA). In our study, rats were induced with complete freund's adjuvant (CFA) to be animal models for studying the RA pathogenesis. Microtubule-associated Serine/Threonine-protein kinase 3 (MAST3) has been documented to play a critical role in regulating the immune response of IBD (Inflammatory bowel disease) and involved in the process of cytoskeleton organization, intracellular signal transduction and peptidyl-serine phosphorylation, but its role in the progression of RA remains unknown and is warranted for investigation. So, we tried our best to investigate the mechanism and signaling pathway of MAST3 in RA progression. In the synovial tissue and FLSs of AA rats, we have found that MAST3 was significantly up-regulated than normal. Furthermore, MAST3 overexpression could promote proliferation and inflammatory response of FLSs. In the aspect of mechanism, we discovered that the expression of MAST3 might involve in NF-κB signaling pathway in RA. On the whole, our results suggested that MAST3 might promote the proliferation and inflammation of FLSs by regulating NF-κB signaling pathway.
30664158 Curculigoside exerts significant anti‑arthritic effects in vivo and in vitro via regul 2019 Mar The present study aimed to investigate the anti‑arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6, IL‑10, IL‑12 and IL‑17A. Furthermore, indices of the thymus and spleen were determined. The anti‑proliferative effects of curculigoside were detected with Cell Counting kit‑8 assays in rheumatoid arthritis‑derived fibroblast‑like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)‑κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen‑induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF‑α, IL‑1β, IL‑6, IL‑10, IL‑12 and IL‑17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration‑dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)‑κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti‑arthritic effects in vivo and in vitro, and the molecular mechanism may be associated with the JAK/STAT/NF‑κB signaling pathway.
30602032 Efficacy of denosumab with regard to bone destruction in prognostic subgroups of Japanese 2019 Jun 1 OBJECTIVES: To evaluate the efficacy of denosumab for progressive bone erosion in risk factor subgroups of Japanese RA patients. METHODS: This study included 340 RA patients on MTX from the dose-response study of Denosumab in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE study-a 12-month, multicentre, randomized, double-blind, placebo-controlled, phase II study). The patients were randomized to receive placebo or denosumab 60 mg every 6 months, 3 months or 2 months. Subgroup analyses involved baseline RF, ACPA, swollen joint count, CRP level, RA duration, ESR and glucocorticoid use. RESULTS: Patients with risk factor positivity generally showed consistent results for the primary endpoint of the change in the modified Sharp erosion score at 12 months from baseline. In the placebo, every 6 months, every 3 months and every 2 months groups, the mean changes in the erosion score, according to the RF status (RF-positive vs -negative subgroups), were 1.18 vs 0.59, 0.25 (P = 0.0601 vs placebo) vs 0.31 (P = 0.0827), 0.21 (P = 0.0422) vs -0.02 (P = 0.0631) and 0.15 (P = 0.0010) vs -0.05 (P = 0.0332), respectively, while the mean changes in the erosion score, according to the ACPA status (ACPA-positive vs -negative subgroups), were 1.30 vs 0.07, 0.26 (P = 0.0142) vs 0.33 (P = 0.2748), 0.16 (P = 0.0058) vs 0.08 (P = 0.7166) and 0.09 (P < 0.0001) vs 0.08 (P = 0.8939), respectively. CONCLUSION: Denosumab is a potentially useful treatment option for RA patients who are positive for RF, ACPA and other possible risk factors. TRIAL REGISTRATION: JAPIC Clinical Trials Information, http://www.clinicaltrials.jp/user/cteSearch_e.jsp, JapicCTI-101263.
30272996 Critical role of IL-1α in IL-1β-induced inflammatory responses: cooperation with NF-κBp 2019 Feb The IL-1 cytokines are considered among the first family of cytokines that orchestrate acute and chronic inflammatory diseases. Both IL-1β and IL-1α are members of the IL-1 family; however, their distinct roles in the inflammatory processes remain poorly understood. We explored the role of IL-1α in IL-1β-activated signaling pathways causing synovial inflammation in rheumatoid arthritis (RA). Using synovial fibroblasts isolated from RA joints, we found that IL-1β significantly stimulated IL-1α expression, which was selectively inhibited by blocking the NF-κB pathway. Knockdown of IL-1α using small interfering RNA abolished IL-1β-induced pro-IL-1α and pro-IL-1β expression and suppressed inflammation. Native and chromatin immunoprecipitation studies showed that IL-1α cooperates in NF-κBp65 binding to the distal region of IL-1α promoter and to the proximal region of IL-1β promoter upstream of the transcription start site to stabilize their gene transcription. Molecular dynamics simulation of IL-1α or IL-1β binding to IL-1 receptor showed distinct interaction sites that corroborate with the ability of IL-1α to differentially activate phosphorylation of signaling proteins compared with IL-1β. Our study highlights the importance of IL-1α in mediating IL-1β-induced inflammation in addition to maintaining its expression and providing a rationale for targeting IL-1α to minimize the role of IL-1β in inflammatory diseases like RA.-Singh, A. K., Fechtner, S., Chourasia, M., Sicalo, J., Ahmed, S. Critical role of IL-1α in IL-1β-induced inflammatory responses: cooperation with NF-κBp65 in transcriptional regulation.
31507120 A Platelet's Guide to Synovitis. 2019 Jul Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.
31804216 CONSEQUENCES OF MICROSEQUENCES OF MICROCIRCULATORY DISTRURBANCES OF ORAL MUCOSA IN MODELIN 2019 Oct Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia and the destruction of cartilage and bone with unclear morphogenesis of pathological changes in oral cavity. Simultaneously microcirculatory disturbance is important link of pathogenesis in many pathological conditions in oral cavity with inflammatory consequences. The aim of this study was to determine importance of microcirculatory disturbance of oral mucosa in modeling of rheumatoid arthritis. Experimental investigation has been performed with modeling RA on laboratory white male mice according to described before method. Investigated groups were formed according to severity manifestation as ankle changes using digital calipers measuring. The specimens of soft tissues of the oral cavity were stained with hematoxylin and eosin, according to van Gieson, according to Rego after the routine proceeding. Morphometric studies were performed with estimation of volumes of specific vascular density in microcirculatory bed, density of connective tissue in lamina propria and area of tissue with ischemia. It was detected that disturbance of oral mucosae microvasculature is formed in rheumatoid arthritis with strong correlation relationship between specific densities of microcirculatory bed vessels and rheumatoid arthritis severity (r=0.74). Development of ischemic area indicates strong correlation relationship between ischemic area and rheumatoid arthritis severity also (r=0.72) and it could be connected with changes in microvasculature (r=0.82). Development of sclerotic changes in the lamina propria of the mucosa could is characterized by increased area of connective tissue from 21.37±2.82% to 34.97±2.26 %.
29798700 Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis 2019 May OBJECTIVE: To examine the deterioration of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with abatacept over the long-term. METHODS: We examined 131 patients with RA who had been treated with abatacept for more than 1 year. All patients underwent high-resolution computed tomographic (HRCT) scanning of the chest before administration of abatacept, and we examined deterioration of ILD over a follow-up period after administration of abatacept was initiated. RESULTS: Eleven patients (8.4%) showed deterioration of ILD over a mean follow-up period of 47.8 months. The factors related to ILD deterioration were use of methotrexate (MTX) [odds ratio 12.75, 95% confidence interval (CI) 1.09-148.77], and change in Krebs von-den Lungen-6 (odds ratio 1.00, 95% CI 1.00-1.01), according to multivariate logistic regression analysis. CONCLUSION: MTX in patients with RA treated with abatacept was a risk factor for deterioration of ILD. Discontinuation of MTX should be considered one of treatment reduction to prevent the deterioration of ILD.
31690205 Ulnar Stump Stabilization Using the Flexor Carpi Ulnaris Tendon for the Rheumatoid Wrist. 2019 Dec Background: The objective of this retrospective study was to evaluate the outcomes of ulnar stump stabilization after ulna head resection using the FCU tendon by investigating the rate of postoperative extensor tendon rupture and click on forearm rotation. Methods: Wrist synovectomy (distal radioulnar joint (DRUJ), radiocarpal and midcarpal joints) and ulnar head resection combined with ulnar stump stabilizing procedure were performed in 58 wrists of 53 patients with RA in our hospital. Before operation, the dorsal subluxation ratio (DSR) of the ulnar head was measured with a multi-slice computed tomography (CT) images. The stabilization of ulnar stump after head resection was performed by the value of the DSR or the instability before the operation. Results: There was neither extensor tendon rupture nor click on forearm rotation in all the patients. Smooth forearm rotation was achieved by ulnar head resection and stabilizing procedure for the ulnar stump. The active range of forearm supination and pronation increased significantly from 68° ± 23° (mean ± SD) to 80° ± 10°, and from 69° ± 17° to 74° ± 13°. The grip power increased from 117 ± 62 mmHg to 185 ± 55 mmHg. In the assessment using 3DCT, the preoperative DSR of 54% improved to 8% on the whole (n = 58). In the wrists with extensor tendon rupture (n = 36), the preoperative DSR of 58% improved to 12%. In the wrists without tendon rupture (n = 22), the preoperative DSR of 46% improved to 2%. Conclusions: The operative technique of ulnar stump stabilization using the FCU tendon was one of the suitable procedure to prevent complications after ulnar head resection.
30570827 Impact of Cyclic Citrullinated Peptide Antibody Level on Progression to Rheumatoid Arthrit 2019 Dec OBJECTIVE: To investigate the risk of progression to rheumatoid arthritis (RA) in patients who were cyclic citrullinated peptide (CCP) antibody positive without RA at initial presentation. METHODS: We performed a retrospective cohort study of CCP+ individuals seen at a US tertiary care system between 2009 and 2018 who were without RA or other systemic rheumatic disease by medical record review at the time of CCP antibody positivity. Progression to classifiable RA was determined through medical record review. We investigated the risk of progression to RA overall and stratified by CCP antibody level (low: >1 to 2× the upper limit of normal [ULN]; medium: >2 to 3× ULN; high: >3× ULN). Multivariable Cox regression estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for RA by CCP antibody level. RESULTS: We identified 340 CCP+ patients who were without RA or other rheumatic disease at baseline. During 1,047 person-years of follow-up, 73 patients (21.5%) developed RA. The risk of progression to RA increased with CCP antibody level, with 46.0% (95% CI 34.7-55.3) of patients with high-level CCP antibodies progressing to RA by 5 years. Compared to low CCP antibody level, medium (HR 3.00 [95% CI 1.32-6.81]) and high (HR 4.83 [95% CI 2.51-9.31]) CCP antibody levels were strongly associated with progression to RA, adjusting for age, sex, body mass index, smoking, family history of RA, and rheumatoid factor level. CONCLUSION: Among CCP+ patients without RA, the risk for progression to RA increased substantially with increasing CCP antibody level. This study provides further support for close monitoring for development of RA among CCP+ patients and identifying strategies to mitigate this risk.
31670481 Ultrasound versus magnetic resonance imaging in the evaluation of shoulder joint pathologi 2019 Dec BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease that has a great impact on different joints, may result in their destruction and loss of function. Although the shoulder is affected in a large portion of patients with RA, it does not receive much attention during the follow up of RA. The precise diagnosis of shoulder pain in RA is a clinical challenge and benefits from a reliable imaging modality to detect its exact origin. AIM: To determine the diagnostic accuracy of ultrasound (US) in detecting shoulder joint pathologies in RA, considering magnetic resonance imaging (MRI) as the gold standard. MATERIALS AND METHODS: This cross-sectional, observational study was carried out on 30 RA patients complaining of unilateral or bilateral shoulder pain. Patients were subjected to history taking, clinical shoulder examination, plain X-ray, US examination following a standardized protocol, and MRI. The results were correlated with each other. RESULTS: In comparison with the MRI findings, US showed high accuracy in terms of sensitivity (Sn) and specificity (Sp) in supraspinatus tendinopathy (Sn 96.6%; Sp 93.3%), biceps tenosynovitis (Sn 87.5%; Sp 97.6%), subacromial-subdeltoid bursitis (Sn 72.7%; Sp 95.7%), humeral erosions (Sn 90.5%; Sp 97.3%), and acromioclavicular osteoarthritis (Sn 85.7%; Sp 95.7%). In terms of reliability, the agreement between US and MRI was almost perfect (κ = .9, P < .001). CONCLUSION: US may have a role as the initial imaging modality in RA patients with shoulder pain, as it is highly sensitive and specific in detecting different pathological abnormalities of the shoulder.
30465159 Autoantibodies to heat shock proteins 60, 70, and 90 in patients with rheumatoid arthritis 2019 Jan Heat shock proteins (HSP) have been reported to impact immune responses and to be associated with rheumatoid arthritis (RA). Recently, we provided evidence for a role of autoantibodies to Hsp40 in patients with RA. In this study, we aimed at investigating the humoral autoimmune response to Hsp60, Hsp70, and Hsp90 in RA patients (n = 39). In comparison with healthy controls (n = 40), circulating IgG, IgM, and IgA autoantibodies against Hsp60, Hsp70, and Hsp90 were significantly increased in RA patients. Non-parametric statistical analysis, however, revealed no significant association between anti-HSP and disease activity or disease progression. On the other hand, positive correlations between serum levels of anti-Hsp60 IgG and IL-4 (Th2-like cytokine) or between serum levels of anti-Hsp90 IgG and IFN-ɣ (Th1-like cytokine) were found to be statistically significant in RA. In addition, a significant inverse correlation was found for serum levels of anti-Hsp70 IgM and TNF-α (Th1-like cytokine) in RA. Our results suggest a pronounced anti-Hsp60, anti-Hsp70, and anti-Hsp90 humoral autoimmune response in RA patients that seems not to be directly linked to RA pathophysiology, however, may have a potential modulatory impact on inflammatory status in this disease. Further investigations are needed to clarify the role of anti-HSP autoantibodies in RA.
31376089 Asymmetric and symmetric dimethylarginine concentration as an indicator of cardiovascular 2020 Jan Rheumatoid arthritis (RA) is the most common type of inflammatory arthritis leading to joint damage and physical disability. Cardiovascular diseases (CVDs) are considered a common comorbidity in patients with RA. However, the mechanism underlying its pathogenesis is not definitively explained. Endothelial dysfunction caused by impaired nitric oxide synthesis is an early indicator of cardiovascular disease. Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) the inhibitors of endothelial nitric oxide synthase (NOS) have emerged as novel CVD risk factor determiners. Concerning the unmet need to identify a salutary biomarker for CVD prediction, the purpose of this meta-analysis was to assess the serum/plasma ADMA and SDMA levels in RA patients compared with the healthy controls. A thorough literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar to identify all studies reporting ADMA and/or SDMA levels in RA patients compared with healthy controls. The quality of studies was evaluated using the Newcastle-Ottawa scale (NOS). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was used as the effect size in this study. We also conducted stratified analysis based on assay methods and median age of the participants. Fourteen articles were included. The pooled serum/plasma levels of ADMA were higher in RA patients compared with those of healthy controls (SMD = 1.02, 95% CI = 0.49 to 1.55); However, no statistical differences between RA patients and healthy controls in serum/plasma SDMA levels was seen (SMD = 0.57, 95% CI = -0.21 to 1.36). Subgroup analyses suggested that participants aged > 50 years had higher levels of ADMA rather than controls and the measurement method was a source of heterogeneity for ADMA. According to the results of this meta-analysis, ADMA measurement but not SDMA, can be useful for assessment of endothelial dysfunction as a predictor of CVD risk in RA patients. Prospero registration number: CRD42019121126.
30366573 Role of the intestinal microbiome in autoimmune diseases and its use in treatments. 2019 May The role of the intestinal microbiome in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes is being increasingly appreciated. Many studies have reported that the compositions of the intestinal microbiomes of patients with these autoimmune diseases are different from those of healthy individuals. Analyses of the intestinal microbiome of humans suggest that various factors affect the composition of the intestinal microbiome, including, but not limited to: geographical location, diet, sex, and age. However, patients with rheumatoid arthritis and type 1 diabetes show unique intestinal microbiome profile even after considering these confounding factors. This review will describe the known differences in the microbial composition for each of the aforementioned autoimmune diseases, how it impacts the immune system, and how these compositions may potentially be modulated by treatments with probiotics, prebiotics, and other microbiome altering therapies.
30376345 NMR-Based Serum Metabolomics Revealed Distinctive Metabolic Patterns in Reactive Arthritis 2019 Jan 4 Reactive arthritis (ReA) is a member of seronegative spondyloarthropathy (SSA), which involves an acute/subacute onset of asymmetrical lower limb joint inflammation weeks after a genitourinary/gastrointestinal infection. The diagnosis is clinical because it is difficult to culture the microbes from synovial fluid. Arthritis patients with a similar clinical picture but lapsed history of an immediate preceding infection that do not fulfill the diagnostic criteria of other members of SSA, such as ankylosing spondylitis, psoriatic arthritis, and arthritis associated with inflammatory bowel disease, are labeled as peripheral undifferentiated spondyloarthropathy (uSpA). Both ReA and uSpA patients show a strong association with class I major histocompatibility complex allele, HLA-B27, and a clear association with an infectious trigger; however, the disease mechanism is far from clear. Because the clinical picture is largely dominated by rheumatoid-arthritis (RA)-like features including elevated levels of inflammatory markers (such as ESR, CRP, etc.), these overlapping symptoms often confound the clinical diagnosis and represent a clinical dilemma, making treatment choice more generalized. Therefore, there is a compelling need to identify biomarkers that can support the diagnosis of ReA/uSpA. In the present study, we performed NMR-based serum metabolomics analysis and demonstrated that ReA/uSpA patients are clearly distinguishable from controls and further that these patients can also be distinguished from the RA patients based on the metabolic profiles, with high sensitivity and specificity. The discriminatory metabolites were further subjected to area under receiver operating characteristic curve analysis, which led to the identification of four metabolic entities (i.e., valine, leucine, arginine/lysine, and phenylalanine) that could differentiate ReA/uSpA from RA.
31028550 Humoral immunity to varicella zoster virus is altered in patients with rheumatoid arthriti 2019 Sep INTRODUCTION: The prevalence of herpes zoster (HZ) is high in patients with rheumatologic diseases. The incidence in patients with rheumatoid arthritis (RA) is at least twice as high as in healthy people. Nevertheless, little is known about humoral immunity against varicella zoster virus (VZV), in particular in patients with RA. We, therefore, aimed to retrospectively compare VZV antibody concentrations in a collective of patients with RA in a German outpatient clinic with age- and sex-matched controls without RA. METHODS: We included n = 247 patients with RA from one single university centre as well as n = 250 age- and sex-matched controls from the in-house routine in this retrospective analysis. The concentration of VZV IgG antibody concentration was either available from the records or was measured using an enzyme-linked immunosorbent assay (ELISA). Additionally, avidity for specific IgG was analysed for some of the samples. The antibody concentrations have been compared between the two groups. Moreover, a consecutive subgroup analysis after stratification by age was performed. RESULTS: A total of 68.4% (n = 169) of the included patients were treated with conventional synthetic DMARDs, either as monotherapy or in combination. Biological originator DMARDs were used in 45.8% (n = 113) of the patients, with the majority (85%, n = 96) of them being on tumour necrosis factor (TNF)-inhibiting agents. As the main result of this study, antibody titres for VZV were found to be significantly lower in RA patients compared with healthy controls (p < 0.0001). The observed difference was most pronounced for the older patients being in the sixth and seventh decade. Antibody avidity was high in both groups with a significantly higher avidity among the controls (p = 0.0006). CONCLUSIONS: A possible explanation for the low VZV antibody concentration in RA patients might be premature immunosenescence, which most likely also effects the B cell compartment and humoral immunity. This thesis is emphasised by the significantly higher antibody avidity among the controls. The data also suggest that the increased HZ risk is a consequence of a poor humoral immunity. The available HZ vaccinations should contribute to decreasing the elevated HZ risk in RA patients. KEY POINTS: • Humoral immunity to varicella zoster virus seems to be reduced in patients with RA. • This impaired immunity might contribute to the increased herpes zoster susceptibility in RA patients. • An accelerated immunosenescence in RA could be causative for this finding.