1,006 research outputs found

    Ann Rheum Dis

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    Objective This study was conducted with sera from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and arthritis and lupus-like disease animal models to identify innate immune system-dependent and -independent autoantigens

    Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical characteristics and autoantibody profile of rheumatoid arthritis.

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    Background: Recent evidence suggests that distinction of subsets of rheumatoid arthritis (RA) depending on anticyclic citrullinated peptide antibody (anti-CCP) status may be helpful in distinguishing distinct aetiopathologies and in predicting the course of disease. HLA-DRB1 shared epitope (SE) and peptidylarginine deiminase type 4 (PADI4) genotype, both of which have been implicated in anti-CCP generation, are assumed to be associated with RA. Objectives: To elucidate whether PADI4 affects the clinical characteristics of RA, and whether it would modulate the effect of anti-CCPs on clinical course. The combined effect of SE and PADI4 on autoantibody profile was also analysed. Methods: 373 patients with RA were studied. SE, padi4_94C.T, rheumatoid factor, anti-CCPs and antinuclear antibodies (ANAs) were determined. Disease severity was characterised by cumulative therapy intensity classified into ordinal categories (CTI-1 to CTI-3) and by Steinbrocker score. Results: CTI was significantly associated with disease duration, erosive disease, disease activity score (DAS) 28 and anti-CCPs. The association of anti-CCPs with CTI was considerably influenced by padi4_94C.T genotype (C/C: ORadj=0.93, padj=0.92; C/T: ORadj=2.92, padj=0.093; T/T: ORadj=15.3, padj=0.002). Carriage of padi4_94T exhibited a significant trend towards higher Steinbrocker scores in univariate and multivariate analyses. An association of padi4_94C.T with ANAs was observed, with noteworthy differences depending on SE status (SE2: ORadj=6.20, padj,0.04; SE+: ORadj=0.36, padj=0.02) and significant heterogeneity between the two SE strata (p=0.006). Conclusions: PADI4 genotype in combination with anti- CCPs and SE modulates clinical and serological characteristics of RA

    Review of eating disorders and oxytocin receptor polymorphisms.

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    BACKGROUND AND AIMS: Oxytocin, a nine amino acid peptide synthesised in the hypothalamus, has been widely recognised for its role in anxiolysis, bonding, sociality, and appetite. It binds to the oxytocin receptor (OXTR)-a G-protein coupled receptor-that is stimulated by the actions of oestrogen both peripherally and centrally. Studies have implicated OXTR genotypes in conferring either a risk or protective effect in autism, schizophrenia, and eating disorders (ED). There are numerous DNA variations of this receptor, with the most common DNA variation being in the form of the single nucleotide polymorphisms (SNPs). Two OXTR SNPs have been most studied in relation to ED: rs53576 and rs2254298. Each SNP has the same allelic variant that produces genotypes AA, AG, and GG. In this critical review we will evaluate the putative role of rs53576 and rs2254298 SNPs in ED. Additionally, this narrative review will consider the role of gene-environment interactions in the development of ED pathology. FINDINGS: The OXTR SNPs rs53576 and rs2254298 show independent associations between the A allele and restrictive eating behaviours. Conversely, the G allele of the OXTR rs53576 SNP is associated with binging behaviours, findings that were also evident in neuroanatomy. One study found the A allele of both OXTR SNPs to confer risk for more severe ED symptomatology while the G allele conferred some protective effect. An interaction between poor maternal care and rs2254298 AG/AA genotype conferred increased risk for binge eating and purging in women. CONCLUSIONS: Individual OXTR SNP are unlikely in themselves to explain complex eating disorders but may affect the expression of and/or effectiveness of the OXTR. A growing body of G x E work is indicating that rs53576G homozygosity becomes disadvantageous for later mental health under early adverse conditions but further research to extend these findings to eating pathology is needed. The GWAS approach would benefit this area of knowledge

    A customized monocyte cDNA microarray for diagnosis of rheumatoid arthritis and prognosis of anti-TNF-α therapy

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    Background In rheumatoid arthritis (RA) macrophages (Mf) play a pivotal role. They become highly activated in synovitis and at the cartilage–pannus junction. Furthermore, therapeutic neutralization of molecules produced by activated Mf lead to clinical improvement in RA, and circulating monocytes (MO) of the peripheral blood in patients with RA spontaneously express proinflammatory genes (IL-1β, IL-6, TNF). Methods A custom RA-MO cDNA microarray was generated using differentially expressed genes obtained from gene subtraction and from comparative whole genome wide U133A analysis in normal donors, active and anti-TNF-α created RA patients. Genes were selected using MAS 5.0, multtest and PAM. The custom microarray consists of 313 genes including guide dots, and positive (housekeeping genes and spike controls) and negative controls for image and statistical analysis. Each probe was spotted in 16 replicates. Results The RA-MO chipset-II was validated using the following: non-stimulated and LPS, PMA, Vit.D3+LPS, PMA+LPS stimulated U937 cells; nonstimulated and LPS stimulated healthy donor MO; MO from normal donors (n = 3) and RA patients before and during anti-TNF-α treatment (n = 5 each); and synovial tissue from normal individuals (n = 2) and RA patients (n = 2). Not only LPS/PMA regulated genes but also RA specific and anti-TNF-α regulated genes were validated. In addition, we could clarify whether these genes are differentially transcribed only in MO or whether they can also be found in RA tissue Mf. Our data indicate a high degree of reproducibility that is sufficient for diagnostic applications and therapy monitoring. Conclusion The RA-MO chipset-II microarray is competitive and flexible for enlargement of the number of genes. The current gene selection will contribute to validating the role of monocytes in disease activity, to therapeutic interventions, and may improve the knowledge on the regulation of pathways in activated monocytes in chronic inflammation

    Identification and characterization of leucosis/sarcoma group of viruses. II. Activation and assay of L-R cells

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    Las células L-R descriptas en este trabajo, se obtuvieron por la inoculación de RSV parcialmente defectivo en cultivos de fibroblastos de embrión de pollo C/O. Bajo las condiciones empleadas en este sistema de test no se obtuvo la misma respuesta a los tres diferentes sub grupos virales del grupo Leucosis/Sarcoma que fueron testados. Queda por determinar si esta diferencia, es debida a las características de las cepas virales empleadas, a las células en que se realizó el ensayo o es una característica de los clones empleados en esta experiencia. De acuerdo a los resultados obtenidos no hay ningún tipo de interferencia a falla en la sensibilidad en el test empleado, por la producción de RSV (O) si es que se produce. La reproductibilidad de los resultados, la facilidad con que se realiza el test, el corto periodo de tiempo empleado, comparado con otros métodos y la simpleza del test, hacen de esta metodología un instrumento con grandes posibilidades de aplicación en la práctica del laboratorio de diagnósticoThe L-R cells described here were originated from CIO chick embryo fibroblast and the virus produced alter their activation was assayed in C/O fibroblasts. The fibroblast came from RIF free SPF flock. Under the conditions described here, the clones of L-R cells isolated did not show similar susceptibility to the different virus subgroup tested. Where this phenomenon was due to the susceptibility of the clones, the assay cells system used, or the strain of virus tested, was not determined. The results obtained with samples from field conditions and experimentally inoculated birds, showed that in this procedure the system of testing the RSV (O) production by the L-R cells (if any), did not interfere in the system, nor with the sensitivity of the testFacultad de Ciencias Veterinaria

    Identification and characterization of leucosis/sarcoma group of viruses. II. Activation and assay of L-R cells

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    Las células L-R descriptas en este trabajo, se obtuvieron por la inoculación de RSV parcialmente defectivo en cultivos de fibroblastos de embrión de pollo C/O. Bajo las condiciones empleadas en este sistema de test no se obtuvo la misma respuesta a los tres diferentes sub grupos virales del grupo Leucosis/Sarcoma que fueron testados. Queda por determinar si esta diferencia, es debida a las características de las cepas virales empleadas, a las células en que se realizó el ensayo o es una característica de los clones empleados en esta experiencia. De acuerdo a los resultados obtenidos no hay ningún tipo de interferencia a falla en la sensibilidad en el test empleado, por la producción de RSV (O) si es que se produce. La reproductibilidad de los resultados, la facilidad con que se realiza el test, el corto periodo de tiempo empleado, comparado con otros métodos y la simpleza del test, hacen de esta metodología un instrumento con grandes posibilidades de aplicación en la práctica del laboratorio de diagnósticoThe L-R cells described here were originated from CIO chick embryo fibroblast and the virus produced alter their activation was assayed in C/O fibroblasts. The fibroblast came from RIF free SPF flock. Under the conditions described here, the clones of L-R cells isolated did not show similar susceptibility to the different virus subgroup tested. Where this phenomenon was due to the susceptibility of the clones, the assay cells system used, or the strain of virus tested, was not determined. The results obtained with samples from field conditions and experimentally inoculated birds, showed that in this procedure the system of testing the RSV (O) production by the L-R cells (if any), did not interfere in the system, nor with the sensitivity of the testFacultad de Ciencias Veterinaria

    Proteasome alpha-type subunit C9 is a primary target of autoantibodies in sera of patients with myositis and systemic lupus erythematosus

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    Autoantibodies occur in low frequencies among patients with myositis characterizing only distinct subsets of this disease. Most of these known antibodies are directed to enzymatically active complexes. The 20S proteasome represents an essential cytoplasmatic protein complex for intracellular nonlysosomal protein degradation, and is involved in major histocompatibility complex class I restricted antigen processing. In this study we investigated whether the 20S proteasome complex is an antibody target in myositis and in other autoimmune diseases. 34 sera of poly/dermatomyositis patients were assayed for antiproteasomal antibodies using enzyme-linked immunosorbent assay, immunoblot, and two-dimensional non-equilibrium pH gradient electrophoresis (NEPHGE). Sera was from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, and rheumatoid arthritis; healthy volunteers served as controls. In 62% (21/34) of the cases sera from patients with myositis and in 58% (30/52) of the cases sera from patients with SLE reacted with the 20S proteasome. These frequencies exceeded those of sera from patients with mixed connective tissue disease, rheumatoid arthritis, and healthy controls. The alpha-type subunit C9 of the 20S proteasome was determined to be the predominant target of the autoimmune sera in myositis and SLE. Lacking other frequent autoantibodies in myositis, the antiproteasome antibodies are the most common humoral immune response so far detected in this disease entity
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