Rheumatoid arthritis and ido

Interference with autoimmune-mediated cytokine production is a key yet poorly developed approach to treat autoimmune and inflammatory diseases such as rheumatoid arthritis. Herein, we show that soluble CD83 (sCD83) enhances the resolution of autoimmune antigen-induced arthritis (AIA) by strongly reducing the expression levels of cytokines such as IL-17A, IFNγ, IL-6, and TNFα within the joints. Noteworthy, also the expression of RANKL, osteoclast differentiation, and joint destruction was significantly inhibited by sCD83...

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) augmentation therapy aims to reduce the progression of emphysema, as achieved by life-long weekly slow-drip infusions of plasma-derived affinity-purified human AAT. However, not all AATD patients will receive this therapy, due to either lack of medical coverage or low patient compliance. To circumvent these limitations, attempts are being made to develop lung-directed therapies, including inhaled AAT and locally-delivered AAT gene therapy...

Objective: Rheumatoid arthritis (RA) is characterized by expansion of fibroblast-like synoviocytes (FLS) in inflamed joints and activation of lymphocytes. Tryptophan (trp) is an essential amino acid indispensable for the biosynthesis of proteins and critical for survival of lymphocytes. Indoleamine 2,3-dioxygenase (IDO) that initiates the degradation of trp and tryptophanyl-tRNA synthetase (TTS) essential for tryptophan synthesis, regulate trp bioavailability. Here, we tested the hypothesis that triggered by cytokines, enhanced IDO activity modulate regulatory function of otherwise non-tolerogenic FLS isolated from RA patients...

OBJECTIVES: Tryptophan and its metabolites have been suggested to play a role in inflammatory processes. However, studies in rheumatoid arthritis (RA) are scarce, which prompted us to investigate two cohorts of RA patients to better understand the importance of tryptophan metabolism in this disease. METHODS: Tryptophan and its metabolites were characterised by ELISA in a cross-sectional cohort 1 (81 RA, 55 OA) and a longitudinal cohort 2 (25 RA, 3 visits over 6 months) to investigate discriminatory power between diseases and predicitive value for radiologic outcome, respectively...

In physiological conditions chondrocytes are protected from contact with immunocompetent cells by the extracellular matrix, and transplanted fragments of allogeneic cartilage are not rejected. Cartilage produced by allogeneic chondrocytes, however, evokes the immune response of the recipient and is gradually destroyed. Immunisation by allogeneic chondrocytes is induced by the contact of their surface molecules with cells of the immune system. Chondrocytes constitutively express class I and, in some species, class II major histocompatibility complex (MHC) molecules...

Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients. hCDR1, but not a control peptide, significantly reduced gene expression of IL-1β, TNF-α, MX-1 and BlyS and up-regulated immunosuppressive (TGF-β, FOXP3) molecules in PBMC of pSS patients...

Interleukin 12 (IL-12) is an inflammatory cytokine that promotes the response of the immune system. This cytokine has been implicated as a potent stimulator of several diseases characterized by inflammatory-induced bone destruction, such as rheumatoid arthritis and periodontitis. Yet, the exact role of IL-12 in the development and progress of periodontitis has not been clarified. Several studies have demonstrated a positive correlation between the level of IL-12 and the severity of periodontal destruction. Deletion of IL-12 in mice with periodontitis significantly suppressed the level of bone destruction...

Bone marrow mesenchymal stem cells (BMSC) have been shown to possess immunomodulatory activities, while its role in rheumatoid arthritis (RA) remains unknown. Citrullinated fibrinogen (cfb) has been considered as a specific autoantigen in RA pathogenesis. Our study aims to determine the role of cfb on immunomodulatory function of BMSC. We demonstrated the specific role of toll-like receptor 4 (TLR4)-NFκB pathway in the pro-inflammatory response of BMSC to cfb with increased production of interleukin (IL)-6, IL-8 and chemokine CC motif ligand 2 (CCL2)...

OBJECTIVE: The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA). METHODS: Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay...

OBJECTIVE: To evaluate the efficacy and safety of biosimilars of anti-tumor necrosis factor (TNF)-α agents compared to their reference agents in immune mediated diseases. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the efficacy and safety of biosimilars of anti-TNF-α agents compared to their reference agents in patients with various immune mediated diseases. The outcomes were the rates of clinical response and adverse events among patients treated with biosimilars compared to their reference agents...

BACKGROUND: Immune mediated diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) commonly affect young and adolescent females. Anti-tumor necrosis factor (TNF)-α agents are increasingly used to treat these conditions, but their safety during pregnancy remains unclear. OBJECTIVES: To evaluate the risk of pregnancy related outcomes in patients with various immune mediated diseases treated with anti-TNF-α agents...

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) comprise lymphoid proliferations or lymphomas that arise in patients treated with immunosuppressive drugs for autoimmune diseases, especially rheumatoid arthritis (RA) treated with methotrexate (MTX). MTX has been increasingly administered to patients with RA, resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients. We report herein on four cases of patients with RA, who diagnosed with head and neck region...

Mesenchymal stem cells (MSCs) possess immunomodulatory properties and have potential, however, there have been conflicting reports regarding their effects in rheumatoid arthritis (RA), which causes inflammation and destruction of the joints. Through a comparative analysis of regulatory T (Treg) and IL-10-producing type 1 regulatory T (Tr1) cells, we hypothesized that Tr1 cells enhance the immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy may exert synergistic immunomodulatory effects in an experimental animal model of rheumatoid arthritis (RA)...

Experimental data suggested involvement of tryptophan (Trp) - kynurenine (Kyn) pathway (TKP) in mechanisms of autoimmune, type 1 (T1D), and metabolic, type 2 (T2D), diabetes. However, clinical evaluations of TKP metabolites were limited to T2D. We assessed Trp, Kyn and TKP metabolites: anthranilic (AA), kynurenic (KYNA) and xanthurenic (XA) acids, in plasma samples of fifteen T1D, thirty T2D patients and twenty eight non-diabetic subjects by HPLC-mass spectrometry. Trp concentrations were higher in T1D than in T2D and controls while Kyn concentrations were not changed suggesting down-regulation of indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of TKP, in T1D...

BACKGROUND: The activity of one of the major catechins in Green Tea, the polyphenol (-)-epigallocatechin-3-gallate (EGCG), has been shown to have a variety of health benefits. Recent studies suggest that EGCG can modulate both the innate and adaptive arms of the immune system. The goal of the current studies was to examine the immunomodulatory effects and mechanisms of action of EGCG on experimental arthritis in mice. METHODS: EGCG (10 mg/kg) was administered by oral gavage after CIA induction, while control mice were administered phosphate buffered saline (PBS)...

T follicular helper (Tfh) cells provide help for antigen-specific B cells. We have previously shown that Tfh cell frequency was increased and associated with auto-antibodies in patients with rheumatoid arthritis (RA), suggesting a possible involvement of Tfh cells in its pathogenesis. Mesenchymal stem cells (MSCs) represent a promising alternative cell therapy for RA by modulating T and B cell activation and proliferation. However, it remains unknown whether MSCs have immunoregulation on Tfh cells. In this paper, we have demonstrated that allogeneic MSCs could suppress Tfh cell differentiation in RA patients partly via the production of indoleamine 2,3-dioxygenase (IDO)...

This study aimed to determine whether umbilical cord-derived mesenchymal stem cells (UCMSC) regulate Cadherin-11 (CDH11) expression by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). FLS were isolated from the synovium of RA and osteoarthritis (OA) patients. FLS from RA patients were cocultured with UCMSC in a transwell system. CDH11 mRNA levels in FLS were tested, and levels of soluble factors expressed by UCMSC, such as indoleamine 2,3-dioxygenase (IDO), hepatocyte growth factor (HGF), and interleukin- (IL-) 10, were determined...

The immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) make them an attractive therapeutic tool to treat chronic inflammatory diseases, such as rheumatoid arthritis or Crohn's disease. These indications are characterized by a chronic activation of immune cells that perpetuates the disease. In vitro, when adipose mesenchymal stem cells (ASCs) are cultured with T lymphocytes at the time of stimulation, their proliferation is inhibited. However, these experimental settings do not necessarily fit with what ASCs will face in inflammatory conditions in vivo, where ASCs will likely encounter and interact with already activated immune cells which might affect their immunomodulatory capacity...

OBJECTIVE: Functionally impaired Treg cells expressing abnormally low levels of CTLA-4 have been well documented in rheumatoid arthritis (RA). However, the molecular defect underlying this reduced expression is unknown. The aims of this study were to assess the role of DNA methylation in regulating CTLA-4 expression in Treg cells isolated from RA patients and to elucidate the mechanism of their reduced suppressor function. METHODS: CTLA-4 expression in Treg cells from RA patients and healthy controls was measured by quantitative polymerase chain reaction (PCR) and flow cytometry...

Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The aim of this work was to study the imbalance expressions of indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase (TTS) with RA patients. Forty-nine RA patients and 49 healthy controls were studied. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry in peripheral blood mononuclear cells. The expression of TTS mRNA increased significantly in RA patients when compared with healthy controls and correlated with erythrocyte sedimentation rate (r = 0...