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

ID PMID Title PublicationDate abstract
27544391 Kaleidoscope of autoimmune diseases in HIV infection. 2016 Nov Within the last 30 years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.
27462309 The Gut Microbiota in Immune-Mediated Inflammatory Diseases. 2016 The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID.
27144464 Chemical and Genetic Comparative Analysis of Gentiana crassicaulis and Gentiana macrophyll 2016 Jun Gentiana crassicaulis Duthie ex Burk. and Gentiana macrophylla Pall. are two main sources of Radix Gentianae Macrophyllae (Qinjiao) available in markets, which has a wide range of anti-inflammatory effects and has been extensively used for fighting rheumatoid arthritis. However, they vary in terms of chemical compositions, pharmacological activities, and biomass. In this study, a combined chemical and genetic (HPLC and DNA barcoding) approach was used to compare these two plants. Four predominant bioactive compounds, namely, gentiopicroside, loganic acid, swertiamarin, and sweroside, were used to assess the chemical variations. Based on chemical variations, 15 samples were clustered into two groups through PCA analyses. DNA barcoding utilizing the variable nuclear ITS2 regions were sequenced, aligned, and compared. Together with 61 sequences collected from GenBank, 76 batches of Qinjiao were clustered in two groups according to species origin. The genetic relationships indicated by the ITS2-based NJ tree were consistent with the chemical variations. Thus, the chemical profiles determined by HPLC and DNA profiles obtained from ITS2 region could be applied for the quality control of Qinjiao.
26880081 [The NLRP3 inflammasome: Physiopathology and therapeutic application]. 2016 Apr The innate immune system constitutes the first line of host defense against pathogens. "Nonself", such as exogenous particles or pathogens, triggers an inflammatory response. Inflammasomes are molecular platforms activated upon cellular infection or stress that trigger the maturation of proinflammatory cytokines such as IL-1β. Activation of the NLRP3 inflammasome pathway, the most extensively studied, appears to be the corner stone of many inflammatory diseases, including Crohn's disease, rheumatoid arthritis and gout. Cryopyrine-associated periodic syndromes (CAPS) are NLRP3 inflammasome-associated diseases. Canakinumab (Ilaris(®)) is the only drug approved for CAPS treatment in France. Targeted therapy against NLRP3 inflammasome and IL-1β might be the new anti-inflammatory drugs.
26595025 Implications of Rheumatic Disease and Biological Response-Modifying Agents in Plastic Surg 2015 Dec The preoperative evaluation for any reconstructive or aesthetic procedure requires a detailed history of existing medical conditions and current home medications. The prevalence of rheumatic diseases such as rheumatoid arthritis, gout, and psoriasis is high, but the impact of these chronic illnesses on surgical outcome and the side effects of the powerful medications used for treatment are often underappreciated. In this review, the authors highlight key perioperative considerations specific to rheumatologic diseases and their associated pharmacologic therapies. In particular, the authors discuss the perioperative management of biological response-modifying agents, which have largely become the new standard of therapy for many rheumatic diseases. The literature reveals three key perioperative concerns with biological therapy for rheumatic disease: infection, wound healing delays, and disease flare. However, data on specific perioperative complications are lacking, and it remains controversial whether withholding biological therapy before surgery is of benefit. The risk of these adverse events is influenced by several factors: age, sex, class of biological agent, duration of exposure, dosage, onset and severity of disease, and type of surgical procedure. Overall, it remains best to develop an individualized plan. In younger patients with recent onset of biological therapy, it is reasonable to withhold therapy based on 3 to 5 half-lives of the specific agent. In older patients with a substantial history of rheumatic disease, the decision to discontinue therapy must be weighed and decided carefully in conjunction with the rheumatologist.
26577605 Mast cells: new therapeutic target in helminth immune modulation. 2016 Jan Helminth infection and their secreted antigens have a protective role in many immune-mediated inflammatory disorders such as inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. However, studies have focused primarily on identifying immune protective mechanisms of helminth infection and their secreted molecules on dendritic cells and macrophages. Given that mast cells have been shown to be implicated in the pathogenesis and progression of many inflammatory disorders, their role should also be examined and considered as cellular target for helminth-based therapies. As there is a dearth of studies examining the interaction of helminth-derived antigens and mast cells, this review will focus on the role of mast cells during helminth infection and examine our current understanding of the involvement of mast cells in TH 1/TH 17-mediated immune disorders. In this context, potential mechanisms by which helminths could target the TH 1/TH 17 promoting properties of mast cells can be identified to unveil novel therapeutic mast cell driven targets in combating these inflammatory disorders.
26527853 Identification and molecular docking analysis of active ingredients with medicinal propert 2015 Underutilized plant species has started changing the conception of plants by expanding the use well beyond from foods and fibers to rich source of medicinally important secondary metabolites. Bioactive compounds from natural sources are gaining importance as potential drug candidates towards many inflammatory conditions like Rheumatoid Arthritis (RA). The focus of the present study has been centred to reveal the anti-inflammatory potential of an underutilized fruits of B. sapida. Further efforts towards its medicinal significance may provide relieve from symptoms of RA by reducing the side effects that are observed in available medications. Total 10 compounds in fruit crude methanol extract were identified and quantified by LC-MS/MS analysis followed by the agar well diffusion method for their anti microbial activity. Among all studied micro organism S. aureus was found to surmount the inflammation in RA through domain B of surface protein A (Staphylococcal surface protein A). Identified compounds (having anti-inflammatory properties) were scrutinized for their toxicity and quantitative structure-activity relationship (QSAR) using lazer toxicity and Molinspiration servers respectively. Further, docking studies have been carried out between domain B and studied compounds using AutoDock. Out of 6 anti-inflammtory compounds, quercetin has been identified as the most potent compound in reference to its inhibitory constant (47.01) and binding energy (-5.90 kcal/mol) to bacterial protein. Our data suggest that methanol extract of B. sapida fruit posses medicinally significant anti-inflammatory compounds and thus justifies the use of this fruit as folklore medicine for preventing inflammation related diseases.
26424279 Surface Plasmon Resonance Method to Evaluate Anti-citrullinated Protein/Peptide Antibody A 2015 Surface plasmon resonance (SPR) technique is extremely interesting in immunology because it has the potential to directly visualize biomolecular interactions in real-time monitoring antibody affinity, one of the parameters affecting pathogenicity in autoimmune diseases. Herein we describe the affinity evaluation of anti-citrullinated peptide antibodies (ACPA) to a peptide-based biosensor by SPR. The method describes the purification of ACPA isolated from rheumatoid arthritis (RA) patients using affinity columns, the strategy employed for the immobilization of citrullinated peptides onto a sensor chip, and the evaluation of the specific binding of purified ACPA to immobilized peptides.
26281313 Prevention of methotrexate-induced nephrotoxicity by concomitant administration of garlic 2015 BACKGROUND/AIM: Methotrexate (MTX) has been widely used for treatment of cancer and rheumatoid arthritis, but its use has been limited by its nephrotoxicity. This study was carried out to determine whether garlic exerts a protective effect against MTX-induced nephrotoxicity. MATERIALS AND METHODS: Nephrotoxicity was induced in rats after a single i.p. injection of MTX (20 mg/kg). Garlic extract (1 mL/100 g b.w.) was given orally for 7 days before and after MTX administration. Serum samples were collected to evaluate urea, creatinine, sodium, phosphorous, potassium, and calcium. Reduced glutathione, catalase, adenosine deaminase, nitric oxide, and malondialdehyde were measured in renal tissue. Tubular injury was evaluated by histopathological examination. RESULTS: MTX increased urea and creatinine levels and led to imbalances in some electrolytes. It also depleted renal antioxidant enzyme levels and increased malondialdehyde, adenosine deaminase, and nitric oxide levels. Histopathological examination showed glomerular and tubular alterations. Pretreatment with garlic significantly improved renal function and increased renal antioxidant enzyme activities. Furthermore, garlic reduced renal oxidative stress and prevented alterations in renal morphology. CONCLUSION: Garlic treatment has a reversible biochemical and histological effect upon MTX-induced nephrotoxicity.
26240808 Extragastroesophageal Malignancy-Associated Secondary Achalasia: A Rare Association of Pan 2015 Jul Secondary achalasia or pseudoachalasia is a rare esophageal motor abnormality, which mimics primary achalasia; it is not easily distinguishable from idiopathic achalasia by manometry, radiological examination, or endoscopy. Although the majority of reported pseudoachalasia cases are associated with neoplasms at or near the esophagogastric (EG) junction, other neoplastic processes or even chronic illnesses such as rheumatoid arthritis can lead to the development of pseudoachalasia, for example, mediastinal masses, gastrointestinal (GI) tumors of the liver and biliary tract, and non-GI malignancies. Therefore, even if a patient presents with the typical findings of achalasia, we should be alert to the possibility of other GI malignancies besides EG tumors. For instance, pancreatic cancer was found in the case reported here; only four such cases have been reported in the literature. A 47-year-old man was admitted to our center with a 3-month history of dysphagia. His endoscopic and esophageal manometric findings were compatible with primary achalasia. However, unresponsiveness to diverse conventional achalasia treatments led us to suspect secondary achalasia. An active search led to a diagnosis of pancreatic mucinous cystadenocarcinoma invading the gastric fundus and EG junction. This rare case of pseudoachalasia caused by pancreatic carcinoma emphasizes the need for suspecting GI malignancies other than EG tumors in patients refractory to conventional achalasia treatment.
26134593 Use of dual-energy computed tomography for the evaluation of calcinosis in patients with s 2015 Sep We examined the usefulness of dual-energy computed tomography (DECT) in the evaluation of symptomatic systemic sclerosis (SSc)-related calcinosis of the hands. We performed DECT scan of the hands in 16 patients with symptomatic SSc-calcinosis to better characterize the calcinosis, their locations within the soft tissues, and exclude monosodium urate (MSU) crystal deposition. We also compared their computed tomography (CT) images to plain radiographs of one hand. Pertinent clinical information from this cohort was collected. Sixteen SSc patients underwent DECT and plain X-ray imaging of the hands. Five of the 16 SSc patients in our cohort had overlap disease, either rheumatoid arthritis (RA) and/or myopathy. Calcinosis symptoms included painful deposits (88 %), soft tissue swelling (66 %), and recurrent infections (44 %) from these deposits. On DECT, calcinosis deposits had the same color and density as the bone and no MSU was found. However, their CT images showed better details of the calcinosis locations in the soft tissues as well as the bone destruction, especially if there was overlying bulky deposits or flexion contractures. These deposits were most commonly found in the subcutaneous fat pads of the fingertips, along tendon and muscle groups, or within the carpal tunnel. DECT did not confirm MSU in our cohort with calcinosis. However, CT imaging was superior to plain radiographs in locating these deposits within the soft tissues and may be a useful tool to study SSc-calcinosis affecting the hands, particularly in the setting of progressive hand deformities.
26017241 Mycobacterium haemophilum infection with prominent facial manifestation mimicking leprosy. 2015 Oct Mycobacterium haemophilum is a slow-growing non-tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients. We recently experienced a 69-year-old Japanese woman with this infection who had been under immunosuppressive treatment for recalcitrant rheumatoid arthritis. The patient showed disseminated erythematous plaques and subcutaneous nodules on the face and extremities, and interestingly, the face manifested with a striking "facies leontina" appearance. Biopsy revealed abscess and granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid-fast bacilli, thus necessitating differentiation from lepromatous leprosy. M. haemophilum was identified by molecular characterization as well as by successful culture with iron supplements. Although drug susceptibility testing indicated responsiveness to multiple antibiotics administrated simultaneously for the treatment, it took over 6 months to achieve significant improvement, and we also employed concurrent oral potassium iodide administration and repeated surgical excision. This case highlights the importance of continuous combination therapy for successful outcome in this rare infection. Furthermore, application of potassium iodide for mycobacterial infection warrants further evaluation by accumulating more cases.
25978926 Exploring the relationship between childhood adversity and oral health: An anecdotal appro 2015 Aug During the past two decades, increasing recognition has been given to a relationship between oral health and systemic diseases. Associated systemic conditions include cardiovascular disease, diabetes, low birth weight and preterm births, respiratory diseases, rheumatoid arthritis, obesity, osteoporosis, and, in particular among oral conditions, periodontal disease. Low-grade inflammation is a common denominator linking these disorders. Applying an anecdotal approach and an integrative view, the medical and dental histories of two women document increasing ill health subsequent to incidences of maltreatment and sexual abuse, including oral penetration, at an early age. Comprehensive oral rehabilitation was required in both cases. These cases open for medical insight with regard to their implicit patho-physiology, when integrated with current evidence from neuroscience, endocrinology, and immunology, converging in the concepts of allostasis and allostatic load. In cases such as those presented in this paper, primary care physicians (family doctors, General Practitioners) and dentists may be the first to identify an etiological pattern. This report underlines the importance of increased and enhanced multidisciplinary research cooperation among health professionals. Our hypothesis is that childhood adversity may affect all aspects of human health, including adult oral health.
25891035 From the Acta Prize Lecture 2014: the periodontal-systemic connection seen from a microbio 2015 OBJECTIVE: To give an overview of the periodontal-systemic connection seen from a microbiologist. METHODS: Original research papers, review articles and workshop proceedings were consulted. RESULTS: Periodontal bacteria can cross epithelial cells, enter the circulation, invade endothelial cells, induce endothelial cell dysfunction and activate inflammatory and immune responses. Several studies support the association between periodontitis (PD) and cardiovascular disease. Severe PD involves a risk for development of type 2 diabetes. Maternal PD is moderately associated with adverse pregnancy outcome and pre-eclampsia. Dental plaque can contain respiratory pathogens able to promote chronic obstructive pulmonary disease and pneumonia. Periodontal bacterial DNA has been detected in synovial fluid of patients with rheumatoid arthritis. Minor evidence exists for associations between PD and chronic kidney disease, obesity, cancer, metabolic syndrome and cognitive impairment. Concerns can be raised as to the interpretation of some study results due to heterogeneity in definitions used for PD, too much weight upon in vitro studies with a few selected organisms and failing recognition that the majority of the periodontal microbiota is not yet cultivated. CONCLUSION: Periodontal bacteria may participate in extra-oral infections such as CVD, diabetes, APO, pre-eclampsia, COPD, pneumonia, RA, CKD, obesity, cancer, MetS and cognitive impairment. Most knowledge is based on associations which do not necessarily imply causality. Future studies should reach consensus on the definition of PD and systemic disease outcomes, recognize the full spectrum of the microbiota in PD and bacteremia, including not-yet-cultivated organisms and delineate the clinical significance of genetic strain variations and the role of periodontopathogenic vs gut organisms within atheromatous lesions. For demonstration of causality, large, long-term clinical studies should use well-defined criteria for PD and robust disease outcomes to elucidate the importance of PD intervention and prevention.
25876578 Nontuberculous mycobacterial lung disease accompanied by organizing pneumonia. 2015 We herein report our experience with patients who had nontuberculous mycobacterial lung disease (NTM disease) accompanied by organizing pneumonia (OP). Out of 98 NTM disease patients who had undergone a biopsy or surgical resection, 11 patients had OP that was revealed histologically. After excluding six patients who had OP-related diseases (idiopathic interstitial pneumonia, rheumatoid arthritis, etc.), the remaining five patients were studied. Two of them (a 73-year-old man and a 66-year-old woman) showed common clinical feature: acute-onset symptoms of cough and fever, infiltrating shadows and dramatic improvement following treatment with a corticosteroid and anti-mycobacterial therapy. Our cases demonstrate that NTM disease is sometimes accompanied by OP histologically, and some such cases show common clinical features.
25849852 Systemic sclerosis and risk of venous thromboembolism: A systematic review and meta-analys 2015 Nov BACKGROUND: Several chronic inflammatory disorders, such as rheumatoid arthritis, inflammatory myositis, and systemic vasculitides, have been linked to an increased risk of venous thromboembolism (VTE). However, the data on systemic sclerosis (SSc) remains unclear. METHODS: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of VTE in patients with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Out of 776 potentially relevant articles, five eligible studies were identified and included in the data analysis. The pooled risk ratio of VTE in patients with SSc was 2.51 (95% CI, 1.79-3.54). The statistical heterogeneity of this study was high with an I(2) of 90%. CONCLUSIONS: Our study demonstrated a statistically significant increased VTE risk among patients with SSc.
25828489 Dyspnea and dysphagia from upper airway obstruction after occipitocervical fusion in the p 2015 Apr Upper airway obstruction resulting from overflexion of the craniocervical junction after occipitocervical fusion is a rare but potentially life-threatening complication and is associated with morbidity. The authors retrospectively reviewed the medical records and diagnostic images of 2 pediatric patients who underwent occipitocervical fusion by the Neuro-Spine Program at Texas Children's Hospital and experienced dyspnea and/or dysphagia from new upper airway obstruction in the postoperative period. Patient demographics, operative data, and preoperative and postoperative occiput-C2 angles were recorded. A review of the literature for similar complications after occipitocervical fusion was performed. A total of 13 cases of prolonged upper airway obstruction after occipitocervical fusion were analyzed. Most of these cases involved adults with rheumatoid arthritis. To the best of the authors' knowledge, there have been no previous reports of prolonged upper airway obstruction in children after an occipitocervical fusion. Fixation of the neck in increased flexion (-18° to -5°) was a common finding among these adult and pediatric cases. The authors' cases involved children with micrognathia and comparatively large tongues, which may predispose the oropharynx to obstruction with even the slightest amount of increased flexion. Close attention to a satisfactory fixation angle (occiput-C2 angle) is necessary to avoid airway obstruction after an occipitocervical fusion. Children with micrognathia are particularly sensitive to changes in flexion at the craniocervical junction after occipitocervical fixation.
25523513 Biomarkers for cardiovascular risk assessment in autoimmune diseases. 2015 Feb Autoimmune diseases, such as antiphospholipid syndrome, systemic lupus erythematosus, and rheumatoid arthritis, are characterized by a high prevalence of cardiovascular (CV) disease (CVD), which constitutes the leading causes of morbidity and mortality among such patients. Although such effects are partly explained by a higher prevalence of traditional CV risk factors, many studies indicate that such factors do not fully explain the enhanced CV risk in these patients. In addition, risk stratification algorithms based upon traditional CV risk factors are not as predictive in autoimmune diseases as in the general population. For these reasons, the timely and accurate assessment of CV risk in these high-risk populations still remains an unmet clinical need. An enhanced contribution of different inflammatory components of the immune response, as well as autoimmune elements (e.g. autoantibodies, autoantigens, and cellular response), has been proposed to underlie the incremental CV risk observed in these populations. Recent advances in proteomic tools have contributed to the discovery of proteins involved in CVDs, including some that may be suitable to be used as biological markers. In this review we summarize the main markers in the field of CVDs associated with autoimmunity, as well as the recent advances in proteomic technology and their application for biomarker discovery in autoimmune disease.
25522998 Impact of systemic inflammation and autoimmune diseases on apoA-I and HDL plasma levels an 2015 The cholesterol of high-density lipoproteins (HDLs) and its major proteic component, apoA-I, have been widely investigated as potential predictors of acute cardiovascular (CV) events. In particular, HDL cholesterol levels were shown to be inversely and independently associated with the risk of acute CV diseases in different patient populations, including autoimmune and chronic inflammatory disorders. Some relevant and direct anti-inflammatory activities of HDL have been also recently identified targeting both immune and vascular cell subsets. These studies recently highlighted the improvement of HDL function (instead of circulating levels) as a promising treatment strategy to reduce inflammation and associated CV risk in several diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In these diseases, anti-inflammatory treatments targeting HDL function might improve both disease activity and CV risk. In this narrative review, we will focus on the pathophysiological relevance of HDL and apoA-I levels/functions in different acute and chronic inflammatory pathophysiological conditions.
25048420 Association between indices of clinically-defined periodontitis and self-reported history 2016 Feb AIM: The aim of the current research was to investigate whether possible associations exist between indices of clinically-defined periodontitis and several systemic medical conditions in outpatients referred to a special hospital clinic. METHODS: The study sample consisted of 3360 outpatients aged 45-65 years. Data were collected by means of an oral clinical examination and a self-administered questionnaire. Statistical analysis of the questionnaire items was done with Fisher's exact test and the logistic regression model to assess possible associations between systemic medical conditions as independent variables, and the relative frequency of periodontal pockets ≥5 mm and clinical attachment loss (CAL) of ≥6 mm as dependent variables. RESULTS: The depth of periodontal pockets was significantly associated with male sex, the presence of vascular disease, hypertension, stroke, heart attack, diabetes mellitus, other endocrine diseases, thyroid disease, respiratory allergies, and rheumatoid arthritis. CAL was significantly associated with the mentioned conditions, and also infective endocarditis and chronic obstructive pulmonary disease, but not other endocrine and thyroid disease. CONCLUSIONS: The findings confirm the results from previous investigations in which a number of systemic medical conditions were significantly associated with probing pocket depth and/or CAL.