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ID PMID Title PublicationDate abstract
24066131 Sinomenine suppresses osteoclast formation and Mycobacterium tuberculosis H37Ra-induced bo 2013 Receptor activator of NF-κB ligand (RANKL) is essential for osteoclastogenesis. Targeting RANKL signaling pathways has been an encouraging strategy for treating lytic bone diseases such as osteoporosis and rheumatoid arthritis (RA). Sinomenine (SIN), derived from Chinese medicinal plant Sinomenioumacutum, is an active compound to treat RA, but its effect on osteoclasts has been hitherto unknown. In the present study, SIN was found to ameliorate M. tuberculosis H37Ra (Mt)-induced bone loss in rats with a decreased serum level of TRACP5b and RANKL, and an increased level of osteoprotegerin (OPG). In vitro study also showed that SIN could inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, MMP-9, TRACP were inhibited by SIN in a dose dependent manner. Signal transduction studies showed that SIN could obviously reduce the expression of RANK adaptor molecule TRAF6 and down-regulate RANKL-induced NF-κB activation. It decreased the RANKL-induced p38, JNK posphorylation but not ERK1/2 posphorylation. SIN could also reduce RANKL-mediated calcium influx which is associated with TRAF6/c-Src complex. Finally, SIN suppressed RANKL induced AP-1 and NFAT transcription, as well as the gene expression of NFATc1 and AP-1 components (Fra-1, Fra-2, c-Fos). The protein expression of c-Fos and TRAF6 were also inhibited by SIN after RANKL stimulation. Taken together, SIN could attenuate osteoclast formation and Mt-induced bone loss by mediating RANKL signaling pathways.
24036054 Treat to target: a proposed new paradigm for the management of Crohn's disease. 2015 Jun The traditional management of Crohn's disease, which is based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of Crohn's disease and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity by using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high-risk patients. This review evaluates current literature on this topic and proposes a definition for the concept of treating to targets for Crohn's disease.
23829825 Correlation of interleukin-6 and monocyte chemotactic protein-1 concentrations with cresce 2013 Sep Myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) and glomerular crescent formation. Pathogenic factors in RPGN were analyzed by using SCG/Kj mice, which spontaneously develop MPO-ANCA-associated RPGN. The serum concentration of soluble IL-6R was determined by using ELISA and those of another 23 cytokines and chemokines by Bio-Plex analysis. Sections of frozen kidney tissue were examined by fluorescence microscopy and the CD3(+) B220(+) T cell subset in the spleen determined by a flow cytometry. Concentrations of IL-6 and monocyte chemotactic protein-1 were significantly correlated with the percentages of crescent formation. Anti-IL-6R antibody, which has been effective in patients with rheumatoid arthritis, was administered to SCG/Kj mice to elucidate the role of IL-6 in the development of RPGN. MPO-ANCA titers decreased after administration of anti-IL-6R antibody, but not titers of mizoribine, which is effective in Kawasaki disease model mice. These results suggest that IL-6-mediated signaling is involved in the production of MPO-ANCA.
23690105 Efficacy of core decompression of femoral head to treat avascular necrosis in intravenous 2013 May 7 Core decompression (CD) of the femoral head is one of the effective treatments of avascular necrosis (AVN), especially in the early stages of the disease. To investigate further the value of CD in treating the AVN, this study was performed on patients with symptomatic AVN with different etiologies who were treated with CD. This study was carried out on 25 patients (with the total number of 37 femoral head) who were diagnosed AVN using X-Ray and MRI. The CD treatments for these patients were started soon after the diagnosis. The results were considered as a success if there was no progression of disease confirmed by X Ray or no subsequent operation was required. Modified Ficat staging was used to record changes before and 2 years after CD treatment. Twenty five patients were participated in this study in which 68% (n=17) were female, 32% (n=8) were male, and the average of the age of the patients were 29.58±4.58. Eight of these patients had systemic lupus erythematous (SLE) (32%), 4 rheumatoid arthritis (RA) (16%), 3 with kidney transplant (12%), 1 Takayasu's vasculitis (4%) and 1 Wegner vasculitis (4%). Eight of patients had a history of intravenous injection of Temgesic (32%). In patients using Temgesic the changes in Modified Ficat staging were significantly different before and after CD treatment (P=0.03) in comparison with other groups. And in all 8 Temgesic users AVN progressed to the stage 3 and 4 after CD treatment. This study demonstrated that CD treatment to prevent the changes in the femoral head has been more effective in patients with collagen vascular diseases and kidney transplant than patients using intravenous Temgesic. These patients, in spite of early operation, showed no benefit of CD to prevent the changes in the femoral head.
23623854 A statistical approach for optimization of RANKL overexpression in Escherichia coli: purif 2013 Jul Receptor activator of nuclear factor-κB (RANK) and its cognate ligand (RANKL) is a member of the TNF superfamily of cytokines which is essential in osteobiology and its overexpression has been implicated in the pathogenesis of bone degenerative diseases such as osteoporosis. Therefore, RANKL is considered a major therapeutic target for the suppression of bone resorption in bone metabolic diseases such as rheumatoid arthritis and cancer metastasis. To evaluate the inhibitory effect of potential RANKL inhibitors a sufficient amount of protein is required. In this work RANKL was cloned for expression at high levels in Escherichia coli with the interaction of changing cultures conditions in order to produce the protein in a soluble form. In an initial step, the effect of expression host on soluble protein production was investigated and BL21(DE3) pLysS was the most efficient one found for the production of RANKL. Central composite design experiment in the following revealed that cell density before induction, IPTG concentration, post-induction temperature and time as well as their interactions had a significant influence on soluble RANKL production. An 80% increase of protein production was achieved after the determination of the optimum induction conditions: OD600nm before induction 0.55, an IPTG concentration of 0.3mM, a post-induction temperature of 25°C and a post-induction time of 6.5h. Following RANKL purification the thermal stability of the protein was studied. The interaction of RANKL with SPD304, a patented small-molecule inhibitor of TNF-α, was also studied in a fluorescence binding assay resulting in a Kd value of 14.1 ± 0.5 μM.
23588514 Frequency of sexual dysfunction in women with rheumatic diseases. 2013 Feb OBJECTIVE: To assess the prevalence of sexual dysfunction in women followed up at the Rheumatology Outpatient Clinic of the Hospital Universitário de Brasília and of the Hospital das Clínicas da Universidade de São Paulo with the following rheumatic diseases: systemic lupus erythematosus; rheumatoid arthritis; systemic sclerosis; antiphospholipid antibody syndrome; and fibromyalgia. METHODS: The Female Sexual Function Index (FSfi), obtained by applying a 19-item questionnaire that assesses six domains (sexual desire, arousal, vaginal lubrication, orgasm, sexual satisfaction and pain), was used. RESULTS: This study assessed 163 patients. The mean age was 40.4 years. The prevalence of sexual dysfunction was 18.4%, but 24.2% of the patients reported no sexual activity over the past 4 weeks. Patients with fibromyalgia and systemic sclerosis had the highest sexual dysfunction index (33%). Excluding patients with no sexual activity, the sexual dysfunction rate reaches 24.2%. CONCLUSION: The prevalence of sexual dysfunction found in this study was lower than that reported in the literature. However, 24.2% of the patients interviewed reported no sexual activity over the past 4 weeks, which might have contributed to the low sexual dysfunction index found.
23546287 Cetylpyridinium chloride inhibits receptor activator of nuclear factor-κB ligand-induced 2013 Osteoclasts are responsible for bone erosion in diseases as diverse as osteoporosis, periodontitis, and rheumatoid arthritis. Antiseptic products have received recent attention as potential therapeutic and preventive drugs in human disease. The purpose of this study was to investigate the effect of the antiseptic cetylpyridinium chloride (CPC) on osteoclast formation using mouse bone marrow-derived macrophages (BMMs). CPC inhibited receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast formation in a dose-dependent manner without causing cytotoxicity. The mRNA expression of cathepsin K, calcitonin receptor (CTR), and Prdm1 in osteoclasts was reduced by CPC. In experiments to elucidate its mechanism of action, CPC was found to suppress RANKL-induced expression of c-Fos and nuclear factor of activated T cells (NFATc1), transcription factors that are essential for osteoclast differentiation. CPC also inhibited RANKL-induced activation of extracellular signal-regulated kinase (ERK) and NF-κB and expression of cyclooxygenase (COX)-2. These results collectively suggest that CPC inhibits osteoclast differentiation by suppressing the activation of ERK and NF-κB and reducing the expression of COX-2, c-Fos, and NFATc1. CPC may therefore be a useful drug in the prevention of bone loss.
23532488 Factors affecting range of motion in total knee arthroplasty using high flexion prosthesis 2013 Jan BACKGROUND: High flexion implants have been reported to provide better range of motion (ROM). The few studies analyzing the factors affecting the ROM are scarce. This study aims to find the factors that affect ROM when using a high flex knee design (INDUS knee). MATERIALS AND METHODS: Two hundred and fifty three consecutive patients of total knee arthroplasty (TKA) done by using INDUS knee prosthesis between Sept 2008 and Sept 2009 were included in the study. The cases with osteoarthritis (OA) and Rheumatoid arthritis (RA) were included in study. 5 patients were lost to followup and 248 patients (267 knees, 19 bilateral, 221 OA, and 46 RA) were analyzed for the following factors - sex, age, body mass index (BMI), preoperative ROM, flexion deformity, preoperative total knee score and functional score, time of tourniquet release and patella resurfacing. Subgroup classification using above factors was performed and statistical analysis of effect of all the above factors on final knee ROM was done. Assessment was done preoperatively and at 3 months, 6 months and 1 year postoperatively. The final outcome evaluation was done at one year followup. RESULTS: The mean age was 68.2 years (range 40-89 years) with 79 males and 189 females. The mean knee range improved from 97.62 ± 11° to 132 ± 8°. Factors that positively affect ROM of INDUS knee prosthesis at the end of 1 year were preoperative ROM, total knee score and functional score, and diagnosis of osteoarthritis, whereas BMI, preoperative flexion deformity has a negative influence on final flexion at the end of 1 year. Age and gender of the patients, patella resurfacing, and use of two different tourniquet protocols did not affect the final outcome. CONCLUSION: Preoperative ROM and preoperative functional status are the most important factors affecting final range. Patients should be counseled accordingly and made to understand these factors.
23516008 Ciclosporin use during pregnancy. 2013 May Ciclosporin (cyclosporine) is an immunosuppressive drug first approved for use in organ transplantation to prevent rejection. Ciclosporin is also known to be used for the treatment of psoriasis, rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease, among other indications. While it is recommended that all medications that are not absolutely necessary should be avoided during pregnancy, this may not be an option for many women whose quality of life is significantly impacted without treatment, or for those who must continue immunosuppressive therapy to avoid organ rejection. The purpose of this review is to provide a comprehensive report from the literature of ciclosporin exposure during pregnancy. PubMed, MEDLINE and the Cochrane Database of Systematic Reviews were searched for English-language articles published from 1970 to 2012 that included reports of pregnant women treated at any time during pregnancy with ciclosporin. On an initial search, it was evident that much of the available information is limited to pregnancy after transplant, which suggests that ciclosporin use during pregnancy appears to be associated with premature delivery and low birthweight infants. Comorbidities such as hypertension, pre-eclampsia and gestational diabetes mellitus are also reported at higher incidences than the general population. Medical literature concerning women with autoimmune disorders exposed to ciclosporin during pregnancy are currently limited to case reports and registry data, and, as such, it is difficult to determine if any risks associated with ciclosporin therapy during pregnancy are due to exposure to the drug alone or to pre-existing maternal comorbidities. The literature suggests that ciclosporin therapy during pregnancy should be carefully considered by the treating physician, but may be a safe alternative for patients with autoimmune disease refractory to conventional treatment. Continued monitoring of this patient population remains a key component to understanding the risk factors associated with ciclosporin exposure during pregnancy.
23314920 Plasminogen activator inhibitor-1 in kidney pathology (Review). 2013 Mar Plasminogen activator inhibitor type-1 (PAI-1) inhibits tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which convert plasminogen to plasmin, a strong proteolytic enzyme. Thus, PAI-1 is a primary and negative regulator of plasmin-driven proteolysis. In addition to its main role as an inhibitor of fibrinolysis, PAI‑1 has been implicated as a mediator in other processes, including fibrosis, rheumatoid arthritis, atherosclerosis, tumor angiogenesis and bacterial infections. It also significantly modulates cellular adhesion or migration, wound healing, angiogenesis and tumor cell metastasis. However, in the present study, we have reviewed the literature in relation to different kidney diseases where PAI-1 regulates fibrinolysis and acts independently of proteolysis. PAI-1 is normally produced in trace amounts in healthy kidneys but is synthesized in a wide variety of both acute and chronic diseased kidneys. We reviewed the role of PAI-1 in diabetic kidney nephropathy, chronic kidney disease, hemodialysis, peritoneal dialysis and in kidney transplantation. Increased PAI-1 expression results in accumulation of extracellular matrix (ECM) leading to numerous kidney diseases. Predisposition to some diseases is due to the genetic role of PAI-1 in their development. A number of studies demonstrated that the inhibition of PAI-1 activity or therapy with a mutant PAI-1 increases matrix turnover and reduces glomerulosclerosis by competing with endogenous PAI-1. This strongly suggests that PAI-1 is a valid target in the treatment of fibrotic renal disease. However, net proteolytic activity depends on the delicate balance between its negative regulation by PAI-1 and activation by uPA and tPA. Also, plasmin activated by its inhibitors upregulates activity of other enzymes. Thus, assessment of prognosis for the diseased kidney should include a variety of proteolysis regulators and enzymes.
25380609 Impact of different etiologies of bronchiectasis on the pulmonary function tests. 2015 Mar BACKGROUND: Bronchiectasis develops along the natural course of several respiratory and systemic conditions and induces significant changes in the morphofunctional structure of airways. Our objective was to assess the impact of various causes of bronchiectasis on clinical data, pulmonary function tests, and high-resolution computed tomography (HRCT). METHODS: The present report was a cross-sectional study that was conducted with 112 consecutive patients with bronchiectasis, who were allocated to five groups, as follows: sequelae of tuberculosis, history of non-tuberculosis infection, cystic fibrosis (CF), primary ciliary dyskinesia (PCD), and rheumatoid arthritis. All of the participants underwent spirometry, whole-body plethysmography, measurement of the diffusing capacity for carbon monoxide (DLco), and HRCT. RESULTS: The highest HRCT score was exhibited in patients with CF (6.03 ± 1.03). The values of forced expiratory volume in 1 second (FEV1) (52.2 ± 17.7%) and DLco (74.1 ± 15.2%) were lower in patients with sequelae of tuberculosis. The increase in the residual volume was more accentuated in the patients with CF (193.5 ± 39.5%) and PCD (189 ± 36.4%). By the multivariate analysis, the cause of FEV1 and bronchiectasis, HRCT score, and degree of dyspnea behaved as independent predictors of DLco. CONCLUSION: In individuals with bronchiectasis, the pulmonary function abnormalities are associated with the etiology of the underlying disease.
25135760 Smoking induces overexpression of immediate early genes in active Graves' ophthalmopathy. 2014 Oct BACKGROUND: Cigarette smoking is a risk factor for the development of Graves' ophthalmopathy (GO). In a previous study of gene expression in intraorbital fat, adipocyte-related immediate early genes (IEGs) were overexpressed in patients with GO compared to controls. We investigated whether IEGs are upregulated by smoking, and examined other pathways that may be affected by smoking. METHODS: Gene expression in intraorbital fat was studied in smokers (n=8) and nonsmokers (n=8) with severe active GO, as well as in subcutaneous fat in thyroid-healthy smokers (n=5) and nonsmokers (n=5) using microarray and real-time polymerase chain reaction (PCR). RESULTS: With microarray, eight IEGs were upregulated more than 1.5-fold in smokers compared to nonsmokers with GO. Five were chosen for confirmation and were also overexpressed with real-time PCR. Interleukin-1 beta/IL-1B/(2.3-fold) and interleukin-6/IL-6/(2.4-fold) were upregulated both with microarray and with real-time PCR in smokers with GO compared to nonsmokers. Major histocompatibility complex, class II, DR beta 1/HLA-DRB1/was upregulated with microarray (2.1-fold) and with borderline significance with real-time PCR. None of these genes were upregulated in smokers compared to nonsmokers in subcutaneous fat. CONCLUSIONS: IEGs, IL-1B, and IL-6 were overexpressed in smokers with severe active GO compared to nonsmokers, suggesting that smoking activates pathways associated with adipogenesis and inflammation. This study underlines the importance of IEGs in the pathogenesis of GO, and provides evidence for possible novel therapeutic interventions in GO. The mechanisms activated by smoking may be shared with other conditions such as rheumatoid arthritis.
25117218 IL-1β and IL-18: inflammatory markers or mediators of hypertension? 2014 Dec Chronic inflammation in the kidneys and vascular wall is a major contributor to hypertension. However, the stimuli and cellular mechanisms responsible for such inflammatory responses remain poorly defined. Inflammasomes are crucial initiators of sterile inflammation in other diseases such as rheumatoid arthritis and gout. These pattern recognition receptors detect host-derived danger-associated molecular patterns (DAMPs), such as microcrystals and reactive oxygen species, and respond by inducing activation of caspase-1. Caspase-1 then processes the cytokines pro-IL-1β and pro-IL-18 into their active forms thus triggering inflammation. While IL-1β and IL-18 are known to be elevated in hypertensive patients, no studies have examined whether this occurs downstream of inflammasome activation or whether inhibition of inflammasome and/or IL-1β/IL-18 signalling prevents hypertension. In this review, we will discuss some known actions of IL-1β and IL-18 on leukocyte and vessel wall function that could potentially underlie a prohypertensive role for these cytokines. We will describe the major classes of inflammasome-activating DAMPs and present evidence that at least some of these are elevated in the setting of hypertension. Finally, we will provide information on drugs that are currently used to inhibit inflammasome/IL-1β/IL-18 signalling and how these might ultimately be used as therapeutic agents for the clinical management of hypertension.
25015061 Elevated levels of serum sCXCL16 in systemic lupus erythematosus; potential involvement in 2014 Nov The aim of this study was to investigate the levels and clinical significance of serum soluble chemokine (C-X-C motif) ligand 16 (sCXCL16) in patients with systemic lupus erythematosus (SLE), as well as the sCXCL16 molecule's associations with disease activity and organ damage. Thirty-five patients with SLE, 16 patients with rheumatoid arthritis (RA), and 15 healthy controls were included in this study. The demographic and clinical features of the patients were recorded. The serum levels of sCXCL16 were determined. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). The serum levels of sCXCL16 in the patients with SLE were higher than those in the patients with RA (P = 0.002) or healthy controls (P < 0.0001). The levels in the patients with active SLE were higher than those in the disease inactive patients (P = 0.008). Positive correlations were identified between serum sCXCL16 concentrations and both SLEDAI (r = 0.564; P < 0.0001) and SDI scores (r = 0.396; P = 0.018). Both SLEDAI (P = 0.021) and serum levels of CXCL16 (P = 0.023) decreased after conventional treatment in 12 initial onset cases of SLE patients. Elevated serum sCXCL16 levels were discovered in the SLE patients with cutaneous (P = 0.006) and renal involvement (P = 0.032). Soluble CXCL16 may become a useful serological marker of disease activity and skin and renal involvement in SLE patients; thus, it may be used for evaluation of therapeutic interventions.
24884884 In vitro inhibition of HUVECs by low dose methotrexate - insights into oral adverse events 2014 May 22 BACKGROUND: With socio-economic changes, dentists and maxillofacial surgeons are more and more faced with medically compromised patients. Especially, the admission of antirheumatic drugs has increased remarkably. So dentists and maxillofacial surgeons should be aware of related adverse reactions that affect the craniofacial region. To identify possible cellular effects of disease modifying antirheumatic drugs (DMARDs) we investigated the influence of methotrexate (MTX) on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were incubated with various concentrations of MTX, corresponding to serum concentrations found in rheumatoid arthritis (RA) patients. The effect of MTX on cell proliferation, differentiation as well as mitochondrial activity was measured by use of immunostaining, cell counting and 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: All samples incubated with MTX (1-1000 nM) showed significantly decreased cell viability when compared to controls. Cells were less proliferating, but did not lose their ability to synthesize endothelial proteins. A slight dose dependency of inhibiting effects was demonstrated. The observed differences between control and sample groups were rising with longer duration. CONCLUSION: Because of the crucial role of endothelial cells and their precursor cells in wound healing, a negative influence of MTX on oral health has to be supposed, correlating to clinical observations of adverse reactions in the oral cavity, such as ulcerative or erosive lesions.
24879162 [Discordance between spine and hip Bone Mineral Density measurement using DXA in osteoporo 2014 Jan BACKGROUND: Diagnostic discordance for osteoporosis is the presence of different categories of T-scores in 2 skeletal sites of an individual patient, falling into 2 different diagnostic categories identified by the World Health Organization classification. AIM: To determinate the prevalence and risk factors for T-score discordance between spine and hip measurement sites. METHODS: Demographic data, anthropometric measurements, and risk factors for osteoporosis were derived from a database of 1780 patients referred to the outpatient osteoporosis testing center of the departement of Rheumatology between September 2006 and February 2010. Bone mineral density (BMD) was performed by Dual-energy x-ray absorptiometry (DXA) on L1-L4 lumbar spine and total hips for all cases. Minor discordance was considered when the difference between 2 sites was no more than 1 World Health Organization diagnostic class. Major discordance was present when 1 site is osteoporotic and the other is normal. RESULTS: In 1780 participants (1606 women and 174 males; mean age, 59.5 ± 14.3 years), concordance of T-scores, minor discordance, and major discordance were seen in 49.4%, 45.7%, and 4.8% of the cases, respectively. In both minor and major discordance BMD was lower in lumbar spine than total hips. In univariate and multivariate logistic regression analysis only menopause was identified as risk factors against T-score discordance with p<0.001 and [OR=5.47; IC: 2.61- 12.79]. The others factors: age, gender, BMI, fracture history, corticotherapy, rheumatoid arthritis, tobacco and diabetes were not associated with the T-score discordance. CONCLUSION: Clinicians should expect that at least half of patients tested by DXA will demonstrate T-score discordance between spine and total hip measurement sites. T-score discordance can occur for a variety of reasons related to physiologic and pathologic patient factors as well as the performance or analysis of DXA itself.
24776925 Whole-exome sequencing for the identification of susceptibility genes of Kashin-Beck disea 2014 OBJECTIVE: To identify and investigate the susceptibility genes of Kashin-Beck disease (KBD) in Chinese population. METHODS: Whole-exome capturing and sequencing technology was used for the detection of genetic variations in 19 individuals from six families with high incidence of KBD. A total of 44 polymorphisms from 41 genes were genotyped from a total of 144 cases and 144 controls by using MassARRAY under the standard protocol from Sequenom. Association was applied on the data by using PLINK1.07. RESULTS: In the sequencing stage, each sample showed approximately 70-fold coverage, thus covering more than 99% of the target regions. Among the single nucleotide polymorphisms (SNPs) used in the transmission disequilibrium test, 108 had a p-value of <0.01, whereas 1056 had a p-value of <0.05. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis indicates that these SNPs focus on three major pathways: regulation of actin cytoskeleton, focal adhesion, and metabolic pathways. In the validation stage, single locus effects revealed that two of these polymorphisms (rs7745040 and rs9275295) in the human leukocyte antigen (HLA)-DRB1 gene and one polymorphism (rs9473132) in CD2-associated protein (CD2AP) gene have a significant statistical association with KBD. CONCLUSIONS: HLA-DRB1 and CD2AP gene were identified to be among the susceptibility genes of KBD, thus supporting the role of the autoimmune response in KBD and the possibility of shared etiology between osteoarthritis, rheumatoid arthritis, and KBD.
24657702 Development of a bead-based immunoassay to routinely measure vimentin autoantibodies in th 2014 May INTRODUCTION: Vimentin is an intermediate filament protein generally expressed in the cytosol of many adult cell types, including leukocytes, fibroblasts and endothelial cells. Several tissue and/or injury-specific isoforms of vimentin are known to exist that may trigger autoimmune responses due to aberrant structural or conformational variations. Such scenarios include allograft rejection and certain autoimmune diseases, such as rheumatoid arthritis. The primary objective for this study was to develop a Luminex immunobead assay to quantitate circulating levels of vimentin antibodies and, secondarily, to appraise the feasibility of these autoantibodies as a biomarker for clinical diagnosis. METHODS: Recombinant human vimentin was conjugated to MagPlex® beads using standard carbodiimide/NHS chemistry and coupling efficiency tested and assay parameters determined using a commercial anti-vimentin polyclonal antibody. A limited number of serum samples (n=71) were then tested to evaluate the diagnostic value for future biomarker development efforts. RESULTS: Findings from repeated testing of three distinct batches of assays provide assay range parameters of 0.18-15μg/mL, median inter-assay recovery parameter within 1% of completion, and inter-assay variation (%CV) at 7%. The assay was found to be stable at several conditions with less than 5% loss in a month. Preliminary evaluation of the assay demonstrates significantly (p=0.022) higher circulating levels of anti-vimentin antibodies in 51 cases of renal allograft rejection relative to 20 cases of age-matched controls. CONCLUSION: A direct capture assay for vimentin autoantibodies was developed and analytically validated. Preliminary evaluation of this assay against patient materials was promising and justifies additional testing with larger cohorts in future studies.
24649227 Increased IL-17 production correlates with immunosuppression involving myeloid-derived sup 2013 Jul Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cell mechanisms mediating this relationship have not been elucidated. Th17 cells, which produce the proinflammatory cytokine interleukin 17 (IL-17), have been recognized as one of the key factors in the regulation of inflammatory bowel disease and rheumatoid arthritis. This study demonstrated that, in patients with various types of gastrointestinal cancer, IL-17 production was correlated with myeloid-derived suppressor cell (MDSC) levels and with markers for nutritional impairment, immune suppression and chronic inflammation. IL-17 was significantly higher in patients with various types of gastrointestinal cancer compared to normal volunteers. In addition, IL-17 levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio (NLR) and significantly inversely correlated with cell-mediated immune response indicators [lymphocyte phytohemagglutinin (PHA)-blastogenesis and IL-12 induction] and patient nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism contributing to disease progression through enhancement of immune suppression or cachexia. Controlling the activation of Th17 cells may prove to be a valuable strategy for the treatment of gastrointestinal cancer patients.
24623628 Identification of OppA2 linear epitopes as serodiagnostic markers for Lyme disease. 2014 May Laboratory diagnosis of Lyme disease is based on the serological detection of antibodies against the etiologic agent Borrelia burgdorferi. Current diagnostics are insensitive at detecting early infection, when treatment is most effective. This deficiency results from the limited number of B. burgdorferi antigens expressed in early infection and the use of an insensitive two-tier paradigm, put in place to deal with insufficient specificity associated with the use of whole-protein antigens and/or bacterial lysates as serodiagnostic targets. Whole-protein antigens contain epitopes that are unique to B. burgdorferi as well as cross-reactive epitopes found in other bacteria. One method for overcoming the limitations imposed by cross-reactive epitopes is the use of short peptides containing epitopes unique to B. burgdorferi as antigen targets. This eliminates nonspecific epitopes. Using overlapping peptide libraries, we performed epitope mapping of linear epitopes in oligopeptide permease A2 (OppA2), a member of the oligopeptide permease (Opp) family of peptide transporters, expressed during early B. burgdorferi infection. We identified 9 epitopes, synthesized peptides containing these epitopes, and screened those using panels of blood from patients with early Lyme disease, rheumatoid arthritis (RA), or syphilis or from healthy individuals. Two of the peptides, OppA2 (191-225) (amino acids comprising the peptide are shown in parentheses) and OppA2 (381-400), are highly conserved among the three major pathogenic Borrelia species responsible for most Lyme disease cases in North America and Europe. They detected antibodies in Lyme disease patient sera with sufficient sensitivity and specificity to indicate that they could have value in a serological assay for Lyme disease.