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

ID PMID Title PublicationDate abstract
23917207 Regulation of inflammation by extracellular acidification and proton-sensing GPCRs. 2013 Nov Under ischemic and inflammatory circumstances, such as allergic airway asthma, rheumatoid arthritis, atherosclerosis, and tumors, extracellular acidification occurs due to the stimulation of anaerobic glycolysis. An acidic microenvironment has been shown to modulate pro-inflammatory or anti-inflammatory responses, including cyclooxygenase-2 (COX-2) expression, prostaglandin synthesis, and cytokine expression, in a variety of cell types, and thereby to exacerbate or ameliorate inflammation. However, molecular mechanisms underlying extracellular acidic pH-induced actions have not been fully understood. Recent studies have shown that ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors (GPCRs) can sense extracellular pH or protons, which in turn stimulates intracellular signaling pathways and subsequent diverse cellular responses. In the present review, I discuss extracellular acidic pH-induced inflammatory responses and related responses in inflammatory cells, such as macrophages and neutrophils, and non-inflammatory cells, such as smooth muscle cells and endothelial cells, focusing especially on proton-sensing GPCRs.
23903221 Therapeutic modulators of STAT signalling for human diseases. 2013 Aug The signal transducer and activator of transcription (STAT) proteins have important roles in biological processes. The abnormal activation of STAT signalling pathways is also implicated in many human diseases, including cancer, autoimmune diseases, rheumatoid arthritis, asthma and diabetes. Over a decade has passed since the first inhibitor of a STAT protein was reported and efforts to discover modulators of STAT signalling as therapeutics continue. This Review discusses the outcomes of the ongoing drug discovery research endeavours against STAT proteins, provides perspectives on new directions for accelerating the discovery of drug candidates, and highlights the noteworthy candidate therapeutics that have progressed to clinical trials.
23874059 The Importance of General Self-Efficacy for the Quality of Life of Adolescents with Chroni 2013 Aug We investigated the influence of general self-efficacy perceived by adolescents with chronic conditions and parents on quality of life. This cross-sectional study used the general self-efficacy scale and DISABKIDS condition-generic module to survey adolescents (92/293; 31 %) with type I diabetes, juvenile rheumatoid arthritis, cystic fibrosis, kidney/urological conditions, and neuromuscular disorders; and parents (121/293; 41 %). Self perceived and parents' perceived general self-efficacy of adolescents was compared using paired t-tests, and adolescents' quality of life and general self-efficacy were compared among conditions using analysis of variance. Bivariate correlations between general self-efficacy and quality of life were identified, and multiple regression sought predictors of quality of life after controlling for background variables. Social quality of life was lowest among those with neuromuscular disorders. General self-efficacy was highest among adolescents with cystic fibrosis and lowest among those with urological conditions. Parents' perceptions of general self-efficacy were higher than adolescents' (p ≤ 0.05), although absolute differences were small. General self-efficacy perceived by parents and adolescents was related to emotional, physical, and social quality of life. Adolescents' perceived self-efficacy predicted all quality of life domains. Parents' perceptions of the adolescents self-efficacy predicted the adolescents' social quality of life (β = 0.19; p ≤ 0.01). General self-efficacy of adolescents with chronic conditions as perceived by themselves and their parents is important for adolescents' quality of life. Interventions to improve general self-efficacy should benefit quality of life among these adolescents.
23803739 Vitamin D status is associated with disease activity among rheumatology outpatients. 2013 Jun 26 The co-existence of high prevalence of vitamin D inadequacy among Canadians and high prevalence of systematic autoimmune rheumatic diseases (SARDs) raise the question on relationship between the two situations. OBJECTIVE: To determine vitamin D status in known cases of common SARDs and compare to those with non-autoimmune diseases; further, to evaluate the impact of vitamin D on disease activity in rheumatoid arthritis (RA) cases. METHODS: In a retrospective case-control study design, we evaluated 116 patients in a community clinic classified in two groups, CONTROL GROUP: patients with non-rheumatic disease (n = 56), and Case group: those with rheumatic diseases (n = 60). We compared plasma vitamin D status (25(OH)D), indicators of disease activity and other potential confounders. Further, we determined factors associated with disease activity in RA cases. RESULTS: The plasma 25(OH)D was significantly lower in Case group (64.8 ± 29.8) compared to CONTROL GROUP (86.8 ± 37.7). High number of SARDs outpatients 56%) had considerably low plasma 25(OH)D concentration. RA cases with low plasma 25(OH)D had over five times higher risk of disease activity (OR = 5.15 95% CI 1.16, 22.9; p = 0.031). CONCLUSION: Inadequate vitamin D status in SARDs cases, along with considerably strong association with disease activity in RA cases, indicate the need for proper evaluation of vitamin D status in this clinical population. Moreover, appropriate training should be given to the patients to ensure the intake of the recommended amount of vitamin D per day through diet or supplement.
23765966 An SduI polymorphism at intron 20 of the Chinese Holstein cow STAT4 gene and its effect on 2013 May 13 The signal transducer and activator of transcription (STAT) genes are responsive to a wide range of cytokines, growth factors, and hormones, and thus control important biological processes. In humans, STAT4 mutations have been identified as genetic markers for rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome, whereas little research has been conducted on bovine STAT4 mutations and their potential effects. Herein, 585 Chinese Holstein cows were used to investigate STAT4 mutations and their effects on milk performance traits. One haplotype block, containing g.95879G>A, g.96013G>C, was identified in intron 20 of the bovine STAT4 gene by restriction fragment length polymorphism-polymerase chain reaction and DNA sequencing. Two single nucleotide polymorphisms were significantly associated with milk yield at 305 days (P < 0.05), and with protein percentage (P < 0.05). Chinese Holstein cows with the haplotype GGGG had higher milk yields at 305 days and lower protein percentages. These results suggest that the 2 single nucleotide polymorphisms of STAT4 could be used as genetic markers for milk performance traits in Chinese Holstein cows.
26675053 The usefulness of ultrasound in the diagnostics of Sjögren's syndrome. 2013 Jun Sjögren's syndrome is an autoimmune exocrinopathy which manifests itself with dryness of the eyes and the oral cavity. These symptoms comprise a so-called sicca syndrome (xerostomia and xerophthalmia). Two forms of this disease may be distinguished: primary Sjögren's syndrome which affects salivary glands and secondary Sjögren's syndrome with other autoimmune diseases present such as rheumatoid arthritis, systemic lupus erythematosus or systemic scleroderma. The diagnosis is based on the classification criteria established in 2002 by a group of American and European scientists (American-European Consensus Group), which involve the interview and physical examination as well as serological, histopathological and radiological tests. Most of these examinations show some limitations such as invasiveness, expensiveness or limited accessibility. The latest research suggests that ultrasound examination may appear promising in the diagnostics of the main salivary glands: submandibular and parotid glands. It is an accessible and relatively cheap examination with high sensitivity and specificity values which are comparable to those obtained via conventional means used in the diagnostics of this disease, i.e. biopsy of the minor salivary glands, sialography and scintigraphy, as well as superior to those obtained in sialometry and Schirmer's test. Additionally, ultrasonography correlates with the results of magnetic resonance imaging. Therefore, a number of authors claim that US examination should be included in the classification criteria of Sjögren's syndrome. The aim of this article is to present the diagnostic capacity of the US examination in Sjögren's syndrome using the current ultrasound classification systems based on the grey-scale, Doppler and contrast-enhanced examinations. The latest research confirms that the most valuable diagnostic criterion in Sjögren's syndrome is the heterogeneity of the glandular parenchyma. The outcome of the examination greatly depends on the examiner's experience.
23645835 Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via down 2013 Jun 13 By inhibiting target gene expression, microRNAs (miRNAs) play major roles in various physiological and pathological processes. miR-146a, a miRNA induced upon lipopolysaccharide (LPS) stimulation and virus infection, is also highly expressed in patients with immune disorders such as rheumatoid arthritis, Sjögren's syndrome, and psoriasis. Whether the high level of miR-146a contributes to any of these pathogenesis-related processes remains unknown. To elucidate the function of miR-146a in vivo, we generated a transgenic (TG) mouse line overexpressing miR-146a. Starting at an early age, these TG mice developed spontaneous immune disorders that mimicked human autoimmune lymphoproliferative syndrome (ALPS) with distinct manifestations, including enlarged spleens and lymph nodes, inflammatory infiltration in the livers and lungs, increased levels of double-negative T cells in peripheral blood, and increased serum immunoglobulin G levels. Moreover, with the adoptive transfer approach, we found that the B-cell population was the major etiological factor and that the expression of Fas, a direct target of miR-146a, was significantly dampened in TG germinal center B cells. These results indicate that miR-146a may be involved in the pathogenesis of ALPS by targeting Fas and may therefore serve as a novel therapeutic target.
23635711 Anakinra and tocilizumab enhance survival and function of human islets during culture: imp 2014 Pretreatment culture before islet transplantation represents a window of opportunity to ameliorate the proinflammatory profile expressed by human β-cells in duress. Anakinra (IL-1 receptor antagonist) and tocilizumab (monoclonal IL-6 receptor antibody) are two known anti-inflammatory agents successfully used in the treatment of inflammatory states like rheumatoid arthritis. Both compounds have also been shown to reduce blood glucose and glycosylated hemoglobin in diabetic patients. We therefore sought to evaluate the impact of anakinra and tocilizumab on human β-cells. The islets were precultured with or without anakinra or tocilizumab and then transplanted in a marginal mass model using human islets in immunodeficient mice. Islet viability was evaluated in an in vitro model. The pretreatment culture led to a significantly improved engraftment in treated islets compared to the vehicle. Anakinra and tocilizumab are not toxic to human islets and significantly reduce markers of inflammation and cell death. These results strongly support a pretreatment culture with anakinra and tocilizumab prior to human islet transplantation.
23615835 Complement and autoimmunity. 2013 Jul The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.
23564363 Has total hip arthroplasty in patients 30 years or younger improved? A systematic review. 2013 Aug BACKGROUND: The evolution of total hip arthroplasty (THA) generally has led to improved clinical results. However, THA in very young patients historically has been associated with lower survivorship, and it is unclear whether this, or results pertaining to pain and function, has improved with contemporary THA. QUESTIONS/PURPOSES: We performed a systematic review of the English literature on THA in patients 30 years of age and younger to assess changes in (1) indications; (2) implant selection; (3) clinical and radiographic outcomes; and (4) survivorship when comparing contemporary and historical reports. METHODS: Multiple databases were searched for articles published between 1965 and 2011 that reported clinical and radiographic outcomes of THA in patients 30 years and younger. Sixteen retrospective case series were identified. Surgical indications, implant selection, clinical and radiographic outcomes, and survivorship of patients undergoing THAs before 1988 were compared with those performed in 1988 and after. RESULTS: Reported THAs performed more recently were less likely to be performed for juvenile rheumatoid arthritis than earlier procedures. Cementless fixation became more prevalent in later years. Although clinical outcome scores remained constant, aseptic loosening and revision rates decreased substantially with more contemporary procedures. CONCLUSIONS: This review of the literature demonstrates an improvement in radiographic outcomes and survivorship of THA, but no significant differences in pain and function scores, in very young patients treated over the past two decades when compared with historical controls.
23558519 Risk factors for deep infection after total knee arthroplasty: a meta-analysis. 2013 May OBJECTIVE: Estimated the risk factors for postoperative infection after total knee arthroplasty (TKA) to prevent its occurrence. DESIGN: The meta-analysis collected twelve cohorts or case-control studies which included 548 infected persons in 57,223 general cases. Review Manager 5.0 was operated to assess the heterogeneity and to give an overall estimate of the association of factors with postoperative infection after TKA. RESULTS: The main factors distinctly associated with infection after TKA were BMI (BMI >30: OR = 2.53, 95 % CI 1.25, 5.13; BMI >40: OR = 4.00, 95 % CI 1.23, 12.98), diabetes mellitus (OR = 3.72, 95 % CI 2.30, 6.01), hypertension (OR = 2.53, 95 % CI 1.07, 5.99), steroid therapy (OR = 2.04, 95 % CI 1.11, 3.74), and rheumatoid arthritis (OR = 1.83; 95 % CI 1.42, 2.36). It had no sufficient evidences to reveal that gender could lead to infection after TKA. Osteoarthritis appeared to have a moderately protective effect. Statistical analysis revealed no correlation between urinary tract infection, fixation method, ASA, bilateral operation, age, transfusion, antibiotics, bone graft, and infection. CONCLUSION: There were positive evidences for some certain factors which could be targeted for prevention of the onset of infection, but more studies are needed to define the association of some other controversial factors in infection, like osteoarthritis, gender and so on. The quality of studies also needs to be improved.
23499528 Versatile role of heparanase in inflammation. 2013 Jun 24 Heparanase is the only known mammalian endoglycosidase capable of degrading heparan sulfate glycosaminoglycan, both in extracellular space and within the cells. It is tightly implicated in cancer progression and over the past few decades significant progress has been made in elucidating the multiple functions of heparanase in malignant tumor development, neovascularization and aggressive behavior. Notably, current data show that in addition to its well characterized role in cancer, heparanase activity may represent an important determinant in the pathogenesis of several inflammatory disorders, such as inflammatory lung injury, rheumatoid arthritis and chronic colitis. Nevertheless, the precise mode of heparanase action in inflammatory reactions remains largely unclear and recent observations suggest that heparanase can either facilitate or limit inflammatory responses, when tissue/cell-specific contextual cues may dictate an outcome of heparanase action in inflammation. In this review the involvement of heparanase in modulation of inflammatory reactions is discussed through a few illustrative examples, including neuroinflammation, sepsis-associated lung injury and inflammatory bowel disease. We also discuss possible action of the enzyme in coupling inflammation and tumorigenesis in the setting of inflammation-triggered cancer.
23351696 [Recombinant proteins or monoclonal antibodies: comparative properties and interest in sys 2013 Jan The emergence of biologic therapies, such as monoclonal antibodies or recombinant fusion proteins, have revolutionized the management of autoimmune disorders, in particular rheumatoid arthritis. These biologic agents have been engineered to deplete key cellular populations or to block cytokines or molecules involved in the activation and/or the differentiation of immune cells, such as T cells or B cells. In systemic lupus erythematosus (SLE), a monoclonal antibody directed against the B-cell activating factor of the TNF family (BAFF or BLyS), belimumab, has demonstrated its efficacy in large, randomized and placebo-controlled studies, whereas rituximab, a monoclonal antibody directed against the CD20 expressed by B cells, failed to achieve his primary endpoint in renal and non-renal SLE. Studies on the safety and the efficacy of monoclonal antibodies or recombinant fusion proteins directed against other key molecules involved in the pathogenesis of SLE are ongoing.
23200399 A novel HPLC-electrochemical detection approach for the determination of D-penicillamine i 2013 Jan 15 D-penicillamine is a thiol drug mainly used for Wilson's disease, rheumatoid arthritis and cystinuria. Adverse effects during normal use of the drug are frequent and may include skin lesions. To evaluate its toxic effects in clinical cases an original method based on high performance liquid chromatography coupled to amperometric detection in a specific biological matrix such as skin has been developed. The chromatographic analysis of D-penicillamine was carried out on a C18 column using a mixture of acid phosphate buffer and methanol as the mobile phase. Satisfactory sensitivity was obtained by oxidizing the molecule at +0.95 V with respect to an Ag/AgCl reference electrode. A chemical reduction of D-penicillamine-protein disulphide bonds using dithioerythritol combined with microwaves was necessary for the determination of the total amount of D-penicillamine in skin specimens. A further solid-phase extraction procedure on C18 cartridges was implemented for the sample clean-up. The whole analytical procedure was validated: high extraction yield (>91.0%) and satisfactory precision (RSD<6.8%) values were obtained. It was successfully applied to skin samples from a patient who was previously under a long-term, high-dose treatment with the drug and presented serious D-penicillamine-related dermatoses. Thus, the method seems to be suitable for the analysis of D-penicillamine in skin tissues.
23106505 Effect of Porphyromonas gingivalis on citrullination of proteins by macrophages in vitro. 2013 Sep BACKGROUND: Citrullination of proteins within inflamed periodontal tissues may provide an important link between periodontitis and rheumatoid arthritis. The aim of this study is to determine whether the presence of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) can influence citrullination of proteins by either increasing the amount of local citrullinated protein or influencing the peptidylarginine deiminase (PAD) enzymes found in the monocyte/macrophage population. METHODS: Human peripheral blood monocytes and macrophages were incubated in the presence of live or heat-killed P. gingivalis. Expression of PAD2 and PAD4, PPAD, and citrullinated proteins were assessed by either a combination of real-time polymerase chain reaction, Western blotting, or a colorimetric assay. RESULTS: PPAD was detected only in mononuclear cells incubated in the presence of live P. gingivalis and resulted in increased extracellular citrullination. Endogenous PAD (mRNA and protein) expression was detected in monocytes and macrophages but was not affected by P. gingivalis. CONCLUSION: Although P. gingivalis produces a PAD that can citrullinate extracellular proteins and may contribute to the citrullinated protein load in gingival tissues, it does not appear to affect PAD expression or citrullination by host monocytes or macrophages.
23044001 Resolution of cystic deterioration of the C1-2 articulation with posterior fusion: treatme 2013 May BACKGROUND: The authors previously reported anterior decompression of C1-2 synovial cysts and subsequent posterior fusion in a large series. Although the surgical morbidity and mortality were acceptable, prior reports of stand-alone C1-2 fusion with resolution of cyst compression presumptively by correction of joint instability were intriguing and did not involve the morbidity associated with the transoral procedure. METHODS: Three cases of retroodontoid cysts that resolved after posterior instrumentation and fusion are presented. These cysts were not associated with rheumatoid arthritis. An additional nine cases from the literature in which fusion was performed without cyst extirpation are reviewed. RESULTS: Three patients presented with retroodontoid cysts. Two patients underwent posterior occipitocervical fusion with instrumentation alone. One patient underwent transoral decompression followed by occipitocervical fusion with instrumentation. In this one patient, magnetic resonance imaging performed early after the transoral procedure demonstrated substantial residual cyst. In all cases, follow-up magnetic resonance imaging performed 6-19 months later demonstrated near-complete resolution of the cysts. A literature review was done to find all other similar cases. Demographics, clinical presentation, imaging, and surgical outcome of these cases were analyzed. CONCLUSIONS: In asymptomatic patients with a synovial cyst of the atlantoaxial junction, posterior fusion alone may lead to complete resolution of the cyst; however, in neurologically symptomatic patients with similar lesions, cyst decompression coupled with posterior fusion is recommended to ensure the highest chance of cyst resolution and clinical improvement.
25473438 The prevalence of antinuclear antibodies in the general population of china: a cross-secti 2014 Dec BACKGROUND: The incidence of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis has increased significantly in China. Information about the susceptibility or potential of autoimmune diseases in the general population is lacking. OBJECTIVE: To explore the prevalence of antinuclear antibody (ANA) and its specificities in the general population in China. METHODS: Twenty thousand nine hundred seventy sera samples were taken from the physical examination center in Baoding, China. Indirect immunofluorescence and line immunoassays were used to detect ANA and its specificities, respectively. RESULTS: Samples from females had a higher prevalence of ANA than samples from males (χ(2) = 278.55; P < 0.01). For both sexes, the prevalence of ANA positively correlated with age and there were significant differences among different age groups at 10-year intervals, except the 80 years group (P < 0.05). One thousand two hundred forty-three ANA-positive samples were further analyzed with line immunoassays. There was a significant difference among age groups and between sex groups in terms of the specific autoantibodies (P < 0.01). The autoantibodies with the top-3 positive frequencies were anti-Ro-52, anti-M2, and anti-SSA. CONCLUSIONS: There was a high prevalence of ANA positivity in the general Chinese population that seemed to be influenced by sex and age and correlated with specific autoantibodies.
25294635 Risk of Venous Thromboembolic Events in Pregnant Patients With Autoimmune Diseases: A Popu 2016 Apr OBJECTIVE: The objective of this study is to evaluate the effect of autoimmune disease on the risk of venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnant women. METHODS: Using the Health Care Cost and Utilization Project, Nationwide Inpatient Sample database from 2003 to 2011, the risk of developing DVT, PE, and VTE among pregnant patients with selected autoimmune diseases was estimated using unconditional logistic regression analysis. RESULTS: Our study cohort consisted of 7 917 453 women of which 43 523 had underlying autoimmune diseases. Risk of VTE was high in pregnant women with systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, type 1 diabetes mellitus, ulcerative colitis, and Crohn's disease. CONCLUSION: Most autoimmune diseases considerably increase the risk of VTE. Thromboprophylaxis may be considered in pregnancies with autoimmune disease, particularly those with systemic lupus erythematosus and dermatomyositis.
25193293 Role of DNA/RNA sensors and contribution to autoimmunity. 2014 Dec Innate immune detection and subsequent immune responses rely on the initial recognition of pathogen specific molecular motifs. Foreign nucleic acids are key structures recognised by the immune system, recognition of which occurs mainly through the use of nucleic acid receptors including members of the Toll-like receptors, AIM2-like receptors, RIG-I-like receptors and intracellular DNA receptors. While the immune system is critically important in protecting the host from infection, it is of utmost importance that it is tightly regulated, in order to prevent recognition of self-nucleic acids and the subsequent development of autoimmunity. Defects in the mechanisms regulating such pathways, for example mutations in endonucleases that clear DNA, altered expression of nucleic acid sensors and defects in negative regulators of these signalling pathways involved in RNA/DNA sensing, have all been implicated in promoting the generation of autoimmune responses. This evidence, as reviewed here, suggests that novel therapeutics targeting these sensors and their downstream pathways may be of use in the treatment of patients with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome.
25172313 Massage therapy research review. 2014 Nov Moderate pressure massage has contributed to many positive effects including increased weight gain in preterm infants, reduced pain in different syndromes including fibromyalgia and rheumatoid arthritis, enhanced attentiveness, reduced depression and enhanced immune function (increased natural killer cells and natural killer cell activity).Surprisingly, these recent studies have not been reviewed, highlighting the need for the current review. When moderate and light pressure massage have been compared in laboratory studies, moderate pressure massage reduced depression, anxiety and heart rate, and it altered EEG patterns, as in a relaxation response. Moderate pressure massage has also led to increased vagal activity and decreased cortisol levels. Functional magnetic resonance imaging data have suggested that moderate pressure massage was represented in several brain regions including the amygdala, the hypothalamus and the anterior cingulate cortex, all areas involved in stress and emotion regulation. Further research is needed to identify underlying neurophysiological and biochemical mechanisms associated with moderate pressure massage.