oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2020 ( 41 )

2019 ( 276 )

2018 ( 493 )

2017 ( 479 )

Custom range...

Search Results: 1 - 10 of 328564 matches for " Juan J. Gomez-Reino "
All listed articles are free for downloading (OA Articles)
Page 1 /328564
Display every page Item
Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period
Juan J Gomez-Reino, Loreto Carmona, the BIOBADASER Group
Arthritis Research & Therapy , 2005, DOI: 10.1186/ar1881
Abstract: When initiated early in rheumatoid arthritis (RA), significant control of joint inflammation and damage and improvement in physical function are obtained with disease modifying antirheumatic drugs (DMARDs), alone or in combination with tumor necrosis factor (TNF) antagonists [1]. Three TNF antagonists, infliximab, etanercept, and adalimumab, have demonstrated efficacy in RA [2-4] and are commercially available. The World Health Organization Collaborating Center consensus proposed that RA patients with active disease who have failed to respond to an adequate course of DMARDs are eligible for anti-cytokine therapy [5]. Other guidelines recommend a similar indication for these agents. In other forms of chronic arthritis, TNF antagonists are also recommended for patients whose disease does not respond to non-steroidal anti-inflammatory drugs or DMARDs [6-9].In RA, evidence based on clinical trials suggests that these three drugs are equally effective, though they have distinct structural, pharmacokinetic, and pharmacological properties [10], and differences in their modes of action [11]. Comparable effectiveness has also been found in clinical settings [12]. Nevertheless, a proportion of patients do not benefit from treatment with a certain TNF antagonist, and thus the use of a second antagonist when the first has failed is advocated based on a few clinical reports of small numbers of patients [13-16]. For the other forms of chronic arthritis, this information is still lacking; whether a second TNF antagonist would be effective is a relevant clinical question.In February 2000, the Spanish Society of Rheumatology (SER) launched a registry (Base de Datos de Productos Biológicos de la Sociedad Espa?ola de Reumatología (BIOBADASER)) for patients with rheumatic conditions treated with biologics, including TNF antagonists. Over the last four and half years, 4,706 patients from 95 hospitals have been included in this registry and have been actively followed. Although the empha
Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheumatoid arthritis: a case-control study
Julio Rodriguez-Lopez, Eva Perez-Pampin, Juan J Gomez-Reino, Antonio Gonzalez
Arthritis Research & Therapy , 2005, DOI: 10.1186/ar1849
Abstract: Many studies support an important role for genetic factors in rheumatoid arthritis (RA) susceptibility and progression [1]. Overall, the genetic component has been estimated to account for about 50% of the variance in disease susceptibility, the remainder being environmental and stochastic components. The best known RA genetic factor is the human leukocyte antigen (HLA) gene, where multiple alleles of the DRbeta1 chain that share a common epitope in the third hypervariable region determine disease susceptibility and severity. Other HLA molecules and several non-HLA genes have also been related with RA susceptibility. Among the many genes that have been studied, only two that encode extracellular matrix (ECM) proteases have been explored [2-6], despite the unequivocal involvement of this family of proteins in RA.The ECM proteases comprise a large family of proteins grouped in several subfamilies, including the matrix metalloproteinases (MMPs), the most extensively studied in RA [7-9]. Many MMPs are expressed at increased levels in RA tissues and in synoviocyte cultures in response to inflammatory cytokines, show specificity for joint tissue components and affect the evolution of experimental models of arthritis. Drugs able to inhibit a wide array of MMPs have been tried for the treatment of RA and, although effective in experimental models, human clinical trials had to be discontinued due to intolerable side effects. It is expected that more specific protease inhibitors will retain therapeutic potential without the associated side effects. It is unclear what ECM proteases to target with these drugs, however, because it has been difficult to ascertain the specific participation of each of them in RA. As a group, they are the major actors in the degradation of ECM in RA cartilage and bone. In addition, they increase and perpetuate joint inflammation through the activation of cytokines, chemokines and other proteases by cleavage of their precursors at specific sites [7-
Reference genes for normalization of gene expression studies in human osteoarthritic articular cartilage
Manuel Pombo-Suarez, Manuel Calaza, Juan J Gomez-Reino, Antonio Gonzalez
BMC Molecular Biology , 2008, DOI: 10.1186/1471-2199-9-17
Abstract: Analyses of expression stability in cartilage from 10 patients with hip OA, 8 patients with knee OA and 10 controls without OA were done with classical statistical tests and the software programs geNorm and NormFinder. Results from the three methods of analysis were broadly concordant. Some of the commonly used reference genes, GAPDH, ACTB and 18S RNA, performed poorly in our analysis. In contrast, the rarely used TBP, RPL13A and B2M genes were the best. It was necessary to use together several of these three genes to obtain the best results. The specific combination depended, to some extent, on the type of samples being compared.Our results provide a satisfactory set of previously unused reference genes for qPCR in hip and knee OA This confirms the need to evaluate the suitability of reference genes in every tissue and experimental situation before starting the quantitative assessment of gene expression by qPCR.Osteoarthritis (OA) is the most common rheumatic disease and a leading cause of disability in the elderly [1]. It involves ligaments, subchondral bone, synovium and cartilage [2,3]. Most research in OA has been focused in articular cartilage where the disease becomes highly evident in its late stages. Biochemical changes in chondrocytes and extracellular matrix components are followed by macroscopic lesions including thinning, fibrillation, fissuring and erosion of cartilage that will eventually lead to denudation of subchondral bone. These changes result from active processes that involve matrix destruction and inefficient repair [4-6]. Progress in the management of OA requires better knowledge of the regulation of these processes as they could have a different impact depending on its etiology. The commonest form of OA is idiopathic and appears only in the elderly. Nevertheless, some forms of OA have a genetic cause or are secondary to rheumatic, endocrine, metabolic or neuropathic diseases or to local factors like trauma, infection or avascular necrosis [7
Lack of association of a variable number of aspartic acid residues in the asporin gene with osteoarthritis susceptibility: case-control studies in Spanish Caucasians
Julio Rodriguez-Lopez, Manuel Pombo-Suarez, Myriam Liz, Juan J Gomez-Reino, Antonio Gonzalez
Arthritis Research & Therapy , 2006, DOI: 10.1186/ar1920
Abstract: Current concepts in osteoarthritis (OA) imply an imbalance of cartilage anabolic and catabolic processes in response to mechanical stress with the participation of inflammatory mediators [1]. Recent investigation has also shown that genetic factors account for a substantial portion of OA etiology [2,3]. These two considerations contribute to the interest of a recent report showing that a variant of asporin (ASPN) is a susceptibility factor for OA [4]. This association points to a defect in the anabolic side of cartilage homeostasis, identifies ASPN and transforming growth factor beta as important molecular players in this process, and suggests that regulatory genetic variants are important in OA susceptibility [5,6].ASPN is a new member of the small leucin-rich proteoglycan subfamily of proteins [7,8] that is expressed at low levels in normal cartilage but that is notably increased in OA cartilage [4]. Variant ASPN proteins are due to a microsatellite in the ASPN coding sequence that determines a variable number of aspartic acid (D) residues in the amino terminal region. The D14 allele is associated with increased OA susceptibility in the Japanese (odds ratio = 1.66–2.49, depending on the cohort) [4] due to its strong inhibition of the cartilage anabolic effects induced by transforming growth factor beta [4]. Given the significance of these results, we explored the ASPN effect in Spanish patients with severe knee or hip OA or with hand OA, but we did not find association. This result is similar to findings in UK Caucasians [9] and in the Greek population [10], and together the observations indicate that the ASPN microsatellite does not have a significant effect on OA susceptibility in European Caucasians.Patients were selected from consecutive patients undergoing total hip replacement (THR) or total knee replacement (TKR) and patients complaining of hand OA that were followed in the Rheumatology Unit. THR and TKR patients were included only if surgery has been perfo
Lack of replication of genetic predictors for the rheumatoid arthritis response to anti-TNF treatments: a prospective case-only study
Marian Suarez-Gestal, Eva Perez-Pampin, Manuel Calaza, Juan J Gomez-Reino, Antonio Gonzalez
Arthritis Research & Therapy , 2010, DOI: 10.1186/ar2990
Abstract: Disease activity score (DAS28) was evaluated in 151 anti-TNF treated patients with RA of Spanish ancestry at baseline and every 3 months thereafter. Genotypes of the 16 putative predictor SNPs were obtained by single-base extension. Association between the relative change in DAS28 and SNP genotypes was tested by linear regression. In addition, logistic regression was applied to compare genotypes in non-responders (n = 34) versus good-responders (n = 61) following the EULAR response criteria.None of the analyses showed any significant association between the 16 SNPs and response to anti-TNF treatments at 3 or 6 months. Results were also negative when only patients treated with infliximab (66.9% of the total) were separately analyzed. These negative results were obtained in spite of a very good statistical power to replicate the reported strong associations.We still do not have any sound evidence of genetic variants associated with RA response to anti-TNF treatments. In addition, the possibility we had envisaged of using the results of a recent GWAS for prediction in individual patients should be dismissed.Anti-tumor necrosis factor (anti-TNF) therapies have revolutionized the treatment of rheumatoid arthritis (RA) [1,2]. Three drugs of this type, infliximab, etanercept, and adalimumab, have been used with success in hundreds of thousands patients with RA around the world. New drugs targeting TNF are in development or have been recently approved [3]. The beneficial effects of these drugs include a better quality of life; control of inflammation, stiffness, and pain; and slowing progression to joint erosions and deformity. It seems also that they are able to decrease cardiovascular risk and overall mortality of patients with RA [4,5]. However, there is a significant percentage of patients who do not obtain these advantageous effects [1-3]. In some of these patients, this lack of response is primary, from the start of the treatment, whereas others develop resistance to
Cis-regulation of IRF5 expression is unable to fully account for systemic lupus erythematosus association: analysis of multiple experiments with lymphoblastoid cell lines
Elisa Alonso-Perez, Marian Suarez-Gestal, Manuel Calaza, Tony Kwan, Jacek Majewski, Juan J Gomez-Reino, Antonio Gonzalez
Arthritis Research & Therapy , 2011, DOI: 10.1186/ar3343
Abstract: Expression data from four published microarray hybridisation experiments with lymphoblastoid cell lines (57 to 181 cell lines) were retrieved. Genotypes of 109 IRF5 polymorphisms, including four known functional polymorphisms, were considered. The best linear regression models accounting for the IRF5 expression data were selected by using a forward entry procedure. SLE-associated IRF5 haplotypes were correlated with the expression data and with the best cis-regulatory models.A large fraction of variability in IRF5 expression was accounted for by linear regression models with IRF5 polymorphisms, but at a different level in each expression data set. Also, the best models from each expression data set were different, although there was overlap between them. The SNP introducing an early polyadenylation signal, rs10954213, was included in the best models for two of the expression data sets and in good models for the other two data sets. The SLE risk haplotype was associated with high IRF5 expression in the four expression data sets. However, there was also a trend towards high IRF5 expression with some protective and neutral haplotypes, and the protective haplotypes were not associated with IRF5 expression. As a consequence, correlation between the cis-regulatory best models and SLE-associated haplotypes, regarding either the risk or protective component, was poor.Our analysis indicates that although the SLE risk haplotype of IRF5 is associated with high expression of the gene, cis-regulation of IRF5 expression is not enough to fully account for IRF5 association with SLE susceptibility, which indicates the need to identify additional functional changes in this gene.Systemic lupus erythematosus (SLE) [1-4], Sj?gren's syndrome [5-7], systemic sclerosis [8-11] and primary biliary cirrhosis [12,13] are complex autoimmune diseases with a genetic component that includes among their strongest susceptibility loci the interferon regulatory factor 5 gene (IRF5). There are reports
Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-κB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility
Rebeca Dieguez-Gonzalez, Manuel Calaza, Eva Perez-Pampin, Alejandro Balsa, Francisco J Blanco, Juan D Ca?ete, Rafael Caliz, Luis Carre?o, Arturo R de la Serna, Benjamin Fernandez-Gutierrez, Ana Ortiz, Gabriel Herrero-Beaumont, Jose L Pablos, Javier Narvaez, Federico Navarro, Jose L Marenco, Juan J Gomez-Reino, Antonio Gonzalez
Arthritis Research & Therapy , 2009, DOI: 10.1186/ar2650
Abstract: To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry.Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region.Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.The etiology of rheumatoid arthritis (RA) includes a genetic component that has become amenable to investigation in recent years. A major development has been the availability of large-scale genome-wide association (GWA) studies. The first GWA studies in RA were readily able to confirm the two clearest RA genetic factors – in the human leukocyte antigen region and in the PTPN22 gene [1-3]. In addition, such studies have found other significant associations. Some of these associations have already been confirmed in additional studies, such as the TRAF1-C5 locus and the intergenic region in the 6q23 chromosome [2-5].Two single nucleotide polymorphisms (SNPs) in 6q23, namely rs6920220 and rs13207033 (or its perfect surrogate rs10499194), have exhibited peak association with RA in an independent manner [2]. This finding has been interpreted as indicating the involvement of multiple genetic variants in RA susceptibility [2]. The associated region does not contain any known protein-coding sequence and lacks any evident functional consequence [2,4], but a strong RA candidate
Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure
Elisa Alonso-Perez, Marian Suarez-Gestal, Manuel Calaza, Torsten Witte, Chryssa Papasteriades, Maurizio Marchini, Sergio Migliaresi, Attila Kovacs, Josep Ordi-Ros, Marc Bijl, Maria Jose Santos, Sarka Ruzickova, Rudolf Pullmann, Patricia Carreira, Fotini N. Skopouli, Sandra D'Alfonso, Gian Domenico Sebastiani, Ana Suarez, Francisco J. Blanco, Juan J. Gomez-Reino, Antonio Gonzalez, and for the European Consortium of SLE DNA Collections
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029033
Abstract: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10?4), oral ulcers (P = 6.9×10?4) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested.
Bias in effect size of systemic lupus erythematosus susceptibility loci across Europe: a case-control study
Elisa Alonso-Perez, Marian Suarez-Gestal, Manuel Calaza, Gian Sebastiani, Rudolf Pullmann, Chryssa Papasteriades, Attila Kovacs, Fotini N Skopouli, Marc Bijl, Ana Suarez, Maurizio Marchini, Sergio Migliaresi, Patricia Carreira, Josep Ordi-Ros, Torsten Witte, Sarka Ruzickova, Maria Santos, Nadia Barizzone, Francisco J Blanco, Bernard R Lauwerys, Juan J Gomez-Reino, Antonio Gonzalez, the European Consortium of SLE DNA Collections
Arthritis Research & Therapy , 2012, DOI: 10.1186/ar3818
Abstract: European SLE patients (n = 1,742) and ethnically matched healthy controls (n = 2,101) were recruited at 17 centres from 10 different countries. Only individuals with self-reported ancestry from the country of origin were included. In addition, participants were genotyped for top ancestry informative markers and for 25 SLE associated SNPs. The results were used to compare effect sizes between the Central Eureopan and Southern European subgroups.Twenty of the 25 SNPs showed independent association with SLE, These SNPs showed a significant bias to larger effect sizes in the Southern subgroup, with 15/20 showing this trend (P = 0.019) and a larger mean odds ratio of the 20 SNPs (1.46 vs. 1.34, P = 0.02) as well as a larger difference in the number of risk alleles (2.06 vs. 1.63, P = 0.027) between SLE patients and controls than for Central Europeans. This bias was reflected in a very significant difference in the cumulative genetic risk score (4.31 vs. 3.48, P = 1.8 × 10-32). Effect size bias was accompanied by a lower number of SLE risk alleles in the Southern subjects, both patients and controls, the difference being more marked between the controls (P = 1.1 × 10-8) than between the Southern and Central European patients (P = 0.016). Seven of these SNPs showed significant allele frequency clines.Our findings showed a bias to larger effect sizes of SLE loci in the Southern Europeans relative to the Central Europeans together with clines of SLE risk allele frequencies. These results indicate the need to study risk allele clines and the implications of the polygenic model of inheritance in SLE.The systemic lupus erythematosus (SLE) genetic component has been partially elucidated thanks to large studies that have uncovered more than 30 loci reaching very convincing disease association [1-12]. These studies have shown that a large fraction of the SLE loci (such as STAT4, TNFSF4 or BLK) are shared in the different ethnic groups; however, other loci are not (such as PTPN22,
Replication of recently identified systemic lupus erythematosus genetic associations: a case–control study
Marian Suarez-Gestal, Manuel Calaza, Em?ke Endreffy, Rudolf Pullmann, Josep Ordi-Ros, Gian Sebastiani, Sarka Ruzickova, Maria Jose Santos, Chryssa Papasteriades, Maurizio Marchini, Fotini N Skopouli, Ana Suarez, Francisco J Blanco, Sandra D'Alfonso, Marc Bijl, Patricia Carreira, Torsten Witte, Sergio Migliaresi, Juan J Gomez-Reino, Antonio Gonzalez, the European Consortium of SLE DNA Collections
Arthritis Research & Therapy , 2009, DOI: 10.1186/ar2698
Abstract: We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel–Haenszel approach to account for heterogeneity between sample collections.A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study.Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.Systemic lupus erythematosus (SLE) is a complex autoimmune disease of wide variability in its manifestations and clinical evolution that characteristically involves multiple autoantibodies against ubiquitous nuclear antigens. Its genetic component is very significant, as shown by a sibling recurrence risk ratio of 20 and a 10-fold excess in SLE concordance between monozygotic twins over dizygotic twins [1,2].Linkage studies have indicated that this genetic component is due to multiple low-penetrance common genetic factors [1]. Only a few factors had c
Page 1 /328564
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.