Pathways In Rheumatoid Arthritis Research Articles

Psoriatic Synovitis: Singularity and Potential Clinical Implications.

Psoriatic arthritis (PsA) is an immuno-inflammatory disease with a heterogeneous clinical presentation as affects musculoskeletal tissues (arthritis, enthesitis, spondylitis), skin (psoriasis) and, less frequently, eye (uveitis) and bowel (inflammatory bowel disease). It has been suggested that distinct affected tissues could exhibit different immune-inflammatory pathways so complicating the understanding of the physiopathology of psoriatic disease as well as its treatment. Despite of the key pathogenic and clinical relevance that enthesitis has in PsA, peripheral arthritis is more easily perceived. At the macroscopic level, PsA synovitis has predominantly tortuous, bushy vessels, whereas rheumatoid arthritis (RA) is characterized by mainly straight, branching vessels so reflecting prominent neo-angiogenesis in PsA. Synovial biopsies have demonstrated a similar cellular and molecular picture in PsA and RA, although some differences have been reported at the group level, as higher density of vessels, CD163+ macrophages, neutrophils and mast cells in PsA. In fact, synovial IL-17+ mast cells are significantly increased in PsA and produce more IL-17A compared with RA, and a proof of concept study supports its relevant role in the synovitis of SpA, included PsA. As firstly reported in RA, synovial lymphoid neogenesis is found also in the same proportion of PsA as in RA patients, despite the lack of autoantibodies in PsA. These lymphoid structures are associated with activation of the IL-23/Th17 pathway in RA and seemly in PsA, which could be useful to stratify RA patients. Immunohistochemical and transcriptomic methodologies have still not found synovial biomarkers useful to distinguish psoriatic from rheumatoid synovitis at the patient level. However, modern methodologies, as MALDI-Mass Spectrometry Imaging, applied to the study of synovial tissue have revealed metabolic and lipid signatures which could support clinical decision-making in the diagnosis of PsA and RA and to go further toward the personalized medicine.

Abstract # 3100 Targeted modulation of neurotransmitter receptors on specific leukocyte subpopulations in rheumatoid arthritis

Background and Aim Current treatment strategies for rheumatoid arthritis (RA) including treat-to-target approaches are only partly successful. Therefore, new treatment options are still needed. There is some evidence for a role for dopamine (DA) in the pathogenesis of RA. Moreover, dopaminergic receptors (DR) are expressed on immune cells. The aim of this study was to further investigate the dopaminergic pathway in RA. Methods The expression of DRs (DRD1-5) was examined via flow cytometry in peripheral blood mononuclear cells (PBMC) of patients with RA (n = 5) and of healthy controls (HC, n = 5). In vitro experiments with DR-agonists were performed to determine the effects of DR-stimulation on immune cells. Results All investigated PBMC subpopulations expressed DRs, with the highest expression levels in NK cells and monocytes. Expression of DRD5 tended to be higher in RA NK cells, and DRD1 was upregulated in RA B-cells compared to HC. The activation marker CD69 was detected in all investigated PBMC subpopulations after 6 h and 22 h of stimulation with DR-agonists. Conclusion Our results show that DRs are present on immune cells and their expression seems to be modulated on defined subpopulations during RA. B cells, which are critical in RA, and NK cells appear attractive in context of dopaminergic treatment approaches. Further experiments are ongoing to better define the role of DA on peripheral immune cells during the course of the disease.

Vitamin D, Inflammation and Osteoporosis in Rheumatoid Arthritis

Patients with Rheumatoid Arthritis (RA) commonly develop osteoporosis and fragility fractures. This fact cannot be explained only with the use of glucocorticoids, known to be detrimental for bone health. RA is characterized by a chronic inflammation caused by the continuous activation of innate and adaptive immunity with proinflammatory cytokines overproduction. This process is detrimental for several organs and physiological processes, including the impairment of bone remodeling. We will briefly review the pathogenesis of inflammation-related bone loss in RA, describing well-known and new molecular pathways and focusing on vitamin D and Parathyroid Hormone role.

Dyrk1A promotes the proliferation, migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis via down-regulating Spry2 and activating the ERK MAPK pathway.

Fibroblast-like synoviocytes (FLSs) play an essential role in rheumatoid arthritis (RA) by promoting synovitis, pannus growth and cartilage/bone destruction. Increased proliferation, migration and invasion of FLSs greatly contribute to RA initiation and progression. Dual-specificity tyrosine-regulated kinase 1A (Dyrk1A), a serine/threonine kinase, regulates MAPK pathway activation, and governs the proliferation and differentiation of neuronal progenitor cells and cancer cells. Till now, the expression and possible function of Dyrk1A in RA FLSs have not been explored. In this study, we detected an increased expression of Dyrk1A both in the synovial tissues of RA patients and in a TNF-α-induced FLSs activation model. CCK-8 and Edu assays revealed that Dyrk1A knockdown inhibited TNF-α-induced FLSs proliferation. Moreover, inhibiting Dyrk1A expression apparently prevented the migration and invasion capability of FLSs accompanied by a decreased MMP-3 and -9 expression. To investigate the molecular mechanism through which Dyrk1A modulates FLSs activities, we evaluated the effects of Dyrk1A on Spry2, a negativity modulator of ERK MAPK pathway. Western blot assay demonstrated that Dyrk1A silencing significantly increased Spry2 expression and suppressed the phosphorylation of ERK in TNF-α-treated FLSs. Taken together, our results indicated that Dyrk1A might promote FLSs proliferation, migration and invasion by suppressing Spry2 expression and activating the ERK MAPK signaling pathway in RA.

Classifying Rheumatoid Arthritis gene network signatures for identifying key regulatory molecules and their altered pathways by adopting network biology approach

Rheumatoid Arthritis (RA) is an auto-immune inflammatory disease which abnormally affects synovial joints of the body. Synovial joint consists of synovial fluid lined by the synovial membrane which includes two prominent cell types, i.e., Synovial fibroblast (SF) and Macrophages (MΦ). These two cell types are highly reported as key players in RA. In the present research, RA expression datasets related to SF and MΦ were collected from Gene Expression Omnibus (GEO) to identify the signature molecule associated with RA pathway. These RA datasets which were analyzed at expression level and correlated based on Pearson Correlation coefficient (r-value) for the construction of the biological interactome. These networks were further explored to identify functional crosstalk between signature molecules in RA. Network centrality parameters and functional characterization were taken into consideration based on power law to predict the key regulatory molecules in the pathogenesis of RA. Groups of highly interconnected signature molecules were further validated by using the integrated approach of The International Mouse Phenotyping Consortium, KEGG and Database of Essential Genes. The research analysis accounted for 9 proteins to be significant in the pathogenesis of RA at three leading levels of function i.e., associated with joint like N-Acetyl Glucosamine metabolism, Fibroblast initiation for pannus formation and Th17 initiation for bone degradation. This type of methodology has enabled to explore novel biomarkers against this multifactorial disease, due to which significant combination of therapies will concentrate on multiple pathways associated with RA rather that single protein.

Hei-Gu-Teng Zhuifenghuoluo Granule Modulates IL-12 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a type of chronic systemic inflammatory disease; it has a very complicated pathogenesis, and multiple pathological changes are implicated. Traditional Chinese medicine (TCM) like Tripterygium wilfordii Hook. F. or Sinomenium acutum (Thunb.) Rehd et Wils. has been extensively used for centuries in the treatment of arthritic diseases and been reported effective for relieving the severity of RA. Hei-Gu-Teng Zhuifenghuoluo granule (HGT) which contains Periploca forrestii Schltr., Sinomenium acutum (Thunb.) Rehd et Wils., and Lysimachia paridiformis Franch. var. stenophylla Franch. was a representative natural rattan herb formula for the treatment of RA in China, but the mechanism has not been elucidated. This study aimed at exploring the mechanism of HGT on RA using the bioinformatics analysis with in vivo and in vitro experiment validation. The potential action mechanism was first investigated by bioinformatics analysis via Ingenuity Pathway Analysis (IPA) software. After that, we use experimental validation such as collagen-induced arthritis (CIA) mice model in vivo and U937 cell model in vitro. The bioinformatics results suggested that HGT may have anti-inflammatory characteristic on RA and IL-12 signaling pathway could be the potential key trigger. In vivo experiments demonstrated that HGT ameliorated the symptoms in CIA mice and decreased the production of inflammatory cytokines in both mice ankle joints and serum. Furthermore, HGT effectively inhibited the activation of IL-12R and STAT4 on IL-12 signaling pathway. In vitro experiments showed that HGT inhibited the production of IL-12R and STAT4 induced by IL-12 in lipopolysaccharide- (LPS-) stimulated U937 cells. Moreover, IL-12R knockdown was able to interfere with the inhibition effects of HGT on the production of these cytokines. Our results confirmed the anti-inflammatory property of HGT, which was attributed to its inhibition on IL-12 signaling pathway.

Anti-Inflammatory Effects of HDL in Mice With Rheumatoid Arthritis Induced by Collagen.

To investigate the anti-inflammatory effects of high-density lipoprotein (HDL) in mice with rheumatoid arthritis (RA) induced by collagen. Male DBA/1 mice (8-week-old) were divided into three groups: control (treated with saline), collagen-induced arthritis (CIA), and CIA + HDL. CIA was induced with bovine type II collagen, and after the injection of bovine type II collagen, the CIA + HDL group received an injection of HDL on day 28 followed by HDL injections four times every 3 days. Mice were weighed, the paws were scored, and paw thickness was measured beginning on day 21. Additionally, the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 were measured by ELISA kits, tissue sections of paws were stained with hematoxylin and eosin, and the inflammatory signaling pathway was analyzed by western blotting. We found that the production of pro-inflammatory cytokines TNF-α and IL-6 in mice which received HDL decreased 45.14 and 35.02%, respectively. And we also found that HDL could significantly decrease the level of anti-type-II-collagen IgG2a and inhibit the neutrophil infiltration and cell proliferation and protect the ankle joint from type II collage-induced injury. Western blot analysis indicated that HDL could also inhibit the activation of the NF-κB, MAPK, and ERK signaling pathways in RA mice. HDL can inhibit the inflammation induced by bovine type II collagen and the development of RA.

Identification of significant ego networks and pathways in rheumatoid arthritis.

The objective of this paper is to identify ego networks and pathways in rheumatoid arthritis (RA) based on EgoNet algorithm and pathway enrichment analysis. The ego networks were identified based on the EgoNet algorithm which was comprised four steps: inputting gene expression data and protein-protein interaction data, identifying ego genes based on topological features of genes in background network, collecting ego networks by conducting snowball sampling for each ego gene, and estimating statistical significance of ego networks utilizing permutation test. To further explore the gene compositions of significant ego networks, pathway enrichment analysis was performed for each of them to investigate ego pathways in the progression of RA. We detected 9 ego genes from the background network, such as CREBBP, SMAD2, and YY1. Starting with each ego gene and ending with prediction accuracy dropped, a total of 9 ego networks were identified. Statistical analysis identified two significant ego networks (ego-networks 2 and 4). Ego-network 2 with ego gene SNW1 and ego-network 4 whose ego gene was YY1 both included 10 genes. The results of pathway enrichment analysis showed that signaling by NOTCH (P = 1.11E-07) and oncogene-induced senescence (P = 3.48E-04) were the two ego pathways for RA. Ego networks and pathways identified in this work might be potential therapeutic markers for RA treatment and give a hand for further studies of this disease.

Comparative in silico analyses of Cannabis sativa, Prunella vulgaris and Withania somnifera compounds elucidating the medicinal properties against rheumatoid arthritis

From last decade, there has been progressive improvement in computational drug designing. Several diseases are being cured from different plant extracts and products. Rheumatoid Arthritis (RA) is the most shared disease among auto-inflammatory diseases. Tumour necrosis factor (TNF)-α is associated with RA pathway and has adverse effects. Extensive literature review showed that plant species under study (Cannabis sativa, Prunella vulgaris and Withania somnifera) possess anti-inflammatory, anti-arthritic and anti-rheumatic properties. 13 anti-inflammatory compounds were characterised and filtered out from medicinal plant species and analysed for RA by targeting TNF-α through in silico analyses. By using ligand based pharmacophore generation approach and virtual screening against natural products libraries we retrieved twenty unique molecules that displayed utmost binding affinity, least binding energies and effective drug properties. The docking analyses revealed that Ala-22, Glu-23, Ser-65, Gln-67, Tyr-141, Leu-142, Asp-143, Phe-144 and Ala-145 were critical interacting residues for receptor-ligand interactions. It is proposed that the RA patients should use reported compounds for the prescription of RA by targeting TNF-α. This report is opening new dimensions for designing innovative therapeutic targets to cure RA.

The dual regulation of substance P-mediated inflammation via human synovial mast cells in rheumatoid arthritis

BackgroundNeural pathways are thought to be directly involved in the pathogenesis of rheumatoid arthritis (RA). Although synovial mast cells (MCs) are activated by substance P (SP), the role of MCs in neural pathways in RA remains unknown. The aims of this study were to investigate 1) whether tachykinins are produced by synovial MCs and whether production differs in RA and osteoarthritis (OA) patients, and 2) what is the responsible receptor for SP in synovial MCs. MethodsSynovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery. Cultured synovium-derived MCs were generated by culturing dispersed synovial cells with stem cell factor. SP expression was investigated using immunofluorescence and enzyme immunoassays. Mas-related gene X2 (MrgX2) expression was reduced in human MCs using a lentiviral shRNA silencing technique. ResultsSP expression was localized around the cell membrane in 41% (median) of the MCs in synovium from RA but in only 7% of that from OA, suggesting the activation of MCs. Synovial MCs expressed tachykinin (TAC) 1 mRNA, the expression of which was upregulated by the aggregation of FcɛRI or the addition of aggregated IgG. However, the released SP appeared to be rapidly degraded by MC chymase. Synovial MCs were activated with SP through MrgX2 to release histamine without producing proinflammatory cytokines. ConclusionsActivated synovial MCs may rapidly degrade SP, which may downregulate the SP-mediated activation of synoviocytes in RA. On the other hand, SP activates MCs to induce inflammatory mediators, suggesting the dual regulation of SP-mediated inflammation by MCs in RA.

Aberrant methylation patterns affect the molecular pathogenesis of rheumatoid arthritis

This study aims to investigate DNA methylation signatures in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA), and to explore the relationship with transcription factors (TFs) that help to distinguish RA from osteoarthritis (OA). Microarray dataset of GSE46346, including six FLS samples from patients with RA and five FLS samples from patients with OA, was downloaded from the Gene Expression Omnibus database. RA and OA samples were screened for differentially methylated loci (DMLs). The corresponding differentially methylated genes (DMGs) were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis. A transcriptional regulatory network was built with TFs and their corresponding DMGs. Overall, 280 hypomethylated loci and 561 hypermethylated loci were screened. Genes containing hypermethylated loci were enriched in pathways in cancer, ECM-receptor interaction, focal adhesion and neurotrophin signaling pathways. Genes containing hypomethylated loci were enriched in the neurotrophin signaling pathway. Moreover, we found that CCCTC-binding factor (CTCF), Yin Yang 1 (YY1), v-myc avian myelocytomatosis viral oncogene homolog (c-MYC), and early growth response 1 (EGR1) were important TFs in the transcriptional regulatory network. Therefore, DMGs might participate in the neurotrophin signaling pathway, pathways in cancer, ECM-receptor interaction and focal adhesion pathways in RA. Furthermore, CTCF, c-MYC, YY1, and EGR1 may play important roles in RA through regulating DMGs.

Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study.

In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies, and immunosuppressive treatment were included as covariates. Pathway analysis was performed using GREAT. Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6 and EFCAB4B were hypomethylated, and both genes have previously been associated with RA. We replicated several candidate genes identified in a previous EWAS in treatment-naïve RA singletons. Gene-set analysis indicated the involvement of immunologic signatures and cancer-related pathways in RA. We identified several differentially methylated regions associated with RA, which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of RA.

Interleukin-17 in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients: Correlation with Clinical Presentation, Laboratory Parameters and Activity Indices

Serum interleukin (IL)-17 concentrations have been reported to be increased in systemic lupus erythematosus (SLE), but associations with clinical characteristics are not well understood. Autoimmune diseases such as rheumatoid arthritis (RA), classically believed to be Th1-mediated, are predominantly driven by a Th17 immune response. The aim of the work is to compare the serum levels of IL-17 in patients with SLE and RA, it is correlation with clinical presentations, laboratory findings and disease activity in both diseases. The study was carried out on 3 groups. Group I: 20 patients with SLE. Group II: 20 patients with RA. Group III: 10 of age and sex matched healthy subjects as a control group. In this study, there were no statistical significant differences between the three studied groups regarding disease duration, disease activity, laboratory investigations (except HB, WBC and platelet count). The mean serum level of IL-17 were 173.2±52.11, 82.6±48.17 and 73.07±41.05 for group I (SLE), II (RA) and III (Control) respectively, group I has values statistically higher than other groups, and group II has values statistically higher than group III. Serum IL-17 level was significantly higher in SLE patients compared to healthy group. We concluded that, Serum IL-17 concentration correlates with SLE and RA diseases activity but is significantly elevated in patients with SLE disease. The association of other cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse immune pathways in SLE and RA.

Vía de señalización Wnt en artritis reumatoide

Rheumatoid arthritis (RA) is a chronic systemic inflammatory joint disease characterized by the formation of a pannus and joint bone destruction. This leads to deformity, discapacity and a diminished quality of life and life expectancy. The Wnt signaling pathway plays an important role in a great number of physiological processes, and recently has been implicated in the regulation of key cells in bone homeostasis. Recent studies suggest that this pathway plays a role in the pathophysiology of RA by the overexpression of inhibitors like the Dickkopf1 protein (DKK1) that negatively affects the differentiation and activity of osteoblasts. High circulating levels of this protein have been associated with higher rates of radiological progression and greater disease activity in RA. Not much has been published about this subject in patients with RA, so the role of this pathway and DKK1 in RA it is not entirely clear. More studies in this area could improve our understanding about the differences in RA clinical presentation and prognosis, and even more they could provide new possible therapeutic targets for RA.

Herb Network Analysis for a Famous TCM Doctor's Prescriptions on Treatment of Rheumatoid Arthritis.

Traditional Chinese Medicine (TCM) doctors always prescribe various herbal formulae tailored to individual patients. However, there is still a lack of appropriate methods to study the rule and potential biological basis underlying the numerous prescriptions. Here we developed an Herb-Compound-Target-Disease coherent network approach to analyze 871 herbal prescriptions from a TCM master, Mr. Ji-Ren Li, in his clinical practice on treatment of rheumatoid arthritis (RA). The core herb networks were extracted from Mr. Li's prescriptions. Then, we predicted target profiles of compounds in core herb networks and calculated potential synergistic activities among them. We further found that the target sets of core herbs overlapped significantly with the RA related biological processes and pathways. Moreover, we detected a possible connection between the prescribed herbs with different properties such as Cold and Hot and the Western drugs with different actions such as immunomodulatory and hormone regulation on treatment of RA. In summary, we explored a new application of TCM network pharmacology on the analysis of TCM prescriptions and detected the networked core herbs, their potential synergistic and biological activities, and possible connections with drugs. This work offers a novel way to understand TCM prescriptions in clinical practice.

MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model.

Rheumatoid arthritis (RA) is an autoimmune and progressive systemic disease of unknown etiology. Research shows that fibroblast-like synoviocytes (FLS) participate in the cartilage erosion, synovial hyperplasia, inflammatory cytokine secretion and suggests that fibroblast-like synoviocytes (FLS) display a crucial role in RA pathogenesis. Recent studies have suggested the role of the Wnt signaling pathway in the pathogenesis of RA. In previous study, we identified that increased methyl-CpG-binding protein 2 (MeCP2) reduced the secreted frizzled-related protein 4 (SFRP4) expression in FLS in Arthritic rat model and the DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-azadC) could induce the SFRP4 expression, indicating that DNMT has a key role in the differential expression of SFRP4. MicroRNAs (MiRNAs), which are small non-coding RNAs, are involved in diverse biological functions, regulation of gene expression, pathogenesis of autoimmune disease and carcinogenesis. In light of the directly down-regulation of miR-152 on DNMT1 expression by targeting the 3' untranslated regions of its transcript in nickel sulfide (NiS)-transformed human bronchial epithelial cells, we investigated whether miR-152 is aberrantly expressed and targets DNMT1 in FLS in Arthritic rat model. Our results demonstrated that the expression of miR-152 was specifically down-regulated in Arthritic rat model, whereas up-regulation of miR-152 in FLS resulted in a marked reduction of DNMT1 expression. Further experiments revealed that increased miR-152 indirectly up-regulated the SFRP4 expression, a negative regulator of WNT signaling pathway, by targeting the DNMT1. Moreover, activation of miR-152 expression in FLS could inhibit the canonical Wnt pathway activation and result in a significant decrease of FLS proliferation. MiR-152 and DNA methylation may provide molecular mechanisms for the activation of canonical Wnt pathway in RA. Combination of miR-152 and DNMT1 may be a promising treatment strategy for RA patients in which SFRP4 is inactivated.

Identification of self-antigen-specific T cells reflecting loss of tolerance in autoimmune disease underpins preventative immunotherapeutic strategies in rheumatoid arthritis.

Despite treatment advances, rheumatoid arthritis (RA) is still associated with significant disability, decreased work capacity, and reduced life expectancy. Effective immunotherapies to restore immune tolerance promise greater specificity, lower toxicity, and a longer-term solution to controlling and preventing RA. Design of effective therapies requires a fundamental understanding of the critical immunopathogenetic pathways in RA. This article reviews advances in the understanding of self-antigen-specific T cells in autoimmune diseases including RA and type 1 diabetes, which bring exciting insights to the mechanisms underpinning loss of tolerance and how tolerance could be restored for disease prevention in the preclinical or recent-onset period.

THU0543 Constitutive Activation of STAT3 in Rheumatoid Arthritis Correlates with IL-6 Levels

BackgroundMany cytokines involved in the inflammatory process in rheumatoid arthritis (RA) activate the JAK-STAT pathways. Therapeutic drugs that inhibit these pathways are currently being developed for RA.ObjectivesTo investigate whether there...

Diminished soluble levels of growth arrest specific protein 6 and tyrosine kinase receptor Axl in patients with rheumatoid arthritis.

Growth arrest specific protein 6 (Gas-6) and its tyrosine kinase receptor Axl plays an important role in apoptosis, and regulation of innate immune response, therefore, we investigated their plasma concentrations in Rheumatoid arthritis (RA) patients and correlated them to clinical, laboratory and radiological parameters of the disease. Plasma from 77 RA patients and 50 normal healthy subjects were assayed for plasma Gas6 and Axl levels. Demographic, clinical and serological data were prospectively assessed. Rheumatoid arthritis disease activity was assessed using 28-joint Disease Activity Score (DAS-28) and functional capacity by modified health assessment questionnaire (mHAQ). Standardized x-rays for hands and feet were done to all participants. The level of Gas6 and Axl were significantly decreased in the RA patients compared to those of the healthy control subjects. Levels of Gas6 correlated positively with Axl levels in both patients and healthy control. Gas6 levels were remarkably reduced in those patients with erosive RA than those without. Levels of Gas6 were found to be negatively correlated with the presence of erosive disease and positively correlated with DAS-28, ESR, Leucocytosis and IL6. The plasma concentrations of Gas6 and Axl are altered in RA patients and thus may have a role in RA pathogenesis. Further mechanistic studies on the involvement of all TAM receptors tyrosine kinases pathway in RA are needed to help in understanding the pathogenesis and possibly aid in diagnosis and future treatments of RA especially for patients with erosive disease.

Editorial: Ethnic‐Specific Genetic Analyses in Rheumatoid Arthritis: Incremental Gains but Valuable Contributions to the Big Picture

Editorial: Ethnic‐Specific Genetic Analyses in Rheumatoid Arthritis: Incremental Gains but Valuable Contributions to the Big Picture