497 research outputs found

    Density functional theory study of (OCS)2^-

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    The structural and electronic properties of the carbonyl sulfide dimer anion are calculated using density functional theory within a pseudopotential method. Three geometries are optimized and investigated: C2v and C2 symmetric, as well as one asymmetric structure. A distribution of an excess charge in three isomers are studied by the Hirshfeld method. In an asymmetric (OCS)2^- isomer the charge is not equally divided between the two moieties, but it is distributed as OCS^{-0.6} OCS^{-0.4}. Low-lying excitation levels of three isomers are compared using the time-dependent density functional theory in the Casida approach.Comment: pdf (included all figures): http://www.phy.hr/~goranka/Research/ocs.pd

    Inter-cluster reactivity of Metallo-aromatic and anti-aromatic Compounds and Their Applications in Molecular Electronics: A Theoretical Investigation

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    Local reactivity descriptors such as the condensed local softness and Fukui function have been employed to investigate the inter-cluster reactivity of the metallo-aromatic (Al4Li- and Al4Na-) and anti-aromatic (Al4Li4 and Al4Na4) compounds. We use the concept of group softness and group Fukui function to study the strength of the nucleophilicity of the Al4 unit in these compounds. Our analysis shows that the trend of nucleophilicity of the Al4 unit in the above clusters is as follows; Al4Li- > Al4Na- > Al4Li4 > Al4Na 4 For the first time we have used the reactivity descriptors to show that these clusters can act as electron donating systems and thus can be used as a molecular cathode.Comment: 23 pages, 1 figure and 1 table of conten

    The Transiting System GJ1214: High-Precision Defocused Transit Observations and a Search for Evidence of Transit Timing Variation

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    Aims: We present 11 high-precision photometric transit observations of the transiting super-Earth planet GJ1214b. Combining these data with observations from other authors, we investigate the ephemeris for possible signs of transit timing variations (TTVs) using a Bayesian approach. Methods: The observations were obtained using telescope-defocusing techniques, and achieve a high precision with random errors in the photometry as low as 1mmag per point. To investigate the possibility of TTVs in the light curve, we calculate the overall probability of a TTV signal using Bayesian methods. Results: The observations are used to determine the photometric parameters and the physical properties of the GJ1214 system. Our results are in good agreement with published values. Individual times of mid-transit are measured with uncertainties as low as 10s, allowing us to reduce the uncertainty in the orbital period by a factor of two. Conclusions: A Bayesian analysis reveals that it is highly improbable that the observed transit times is explained by TTV, when compared with the simpler alternative of a linear ephemeris.Comment: Submitted to A&

    CaZF, a Plant Transcription Factor Functions through and Parallel to HOG and Calcineurin Pathways in Saccharomyces cerevisiae to Provide Osmotolerance

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    Salt-sensitive yeast mutants were deployed to characterize a gene encoding a C2H2 zinc finger protein (CaZF) that is differentially expressed in a drought-tolerant variety of chickpea (Cicer arietinum) and provides salinity-tolerance in transgenic tobacco. In Saccharomyces cerevisiae most of the cellular responses to hyper-osmotic stress is regulated by two interconnected pathways involving high osmolarity glycerol mitogen-activated protein kinase (Hog1p) and Calcineurin (CAN), a Ca2+/calmodulin-regulated protein phosphatase 2B. In this study, we report that heterologous expression of CaZF provides osmotolerance in S. cerevisiae through Hog1p and Calcineurin dependent as well as independent pathways. CaZF partially suppresses salt-hypersensitive phenotypes of hog1, can and hog1can mutants and in conjunction, stimulates HOG and CAN pathway genes with subsequent accumulation of glycerol in absence of Hog1p and CAN. CaZF directly binds to stress response element (STRE) to activate STRE-containing promoter in yeast. Transactivation and salt tolerance assays of CaZF deletion mutants showed that other than the transactivation domain a C-terminal domain composed of acidic and basic amino acids is also required for its function. Altogether, results from this study suggests that CaZF is a potential plant salt-tolerance determinant and also provide evidence that in budding yeast expression of HOG and CAN pathway genes can be stimulated in absence of their regulatory enzymes to provide osmotolerance

    Ask yeast how to burn your fats: lessons learned from the metabolic adaptation to salt stress

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    [EN] Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation. Primary defense mechanisms are the massive induction of stress tolerance genes in the nucleus, the activation of cation transport at the plasma membrane, or the production and intracellular accumulation of osmolytes. At the same time and in a coordinated manner, the cell shuts down the expression of housekeeping genes, delays the progression of the cell cycle, inhibits genomic replication, and modulates translation efficiency to optimize the response and to avoid cellular damage. To this fascinating interplay of cellular functions directly regulated by the stress, we have to add yet another layer of control, which is physiologically relevant for stress tolerance. Salt stress induces an immediate metabolic readjustment, which includes the up-regulation of peroxisomal biomass and activity in a coordinated manner with the reinforcement of mitochondrial respiratory metabolism. Our recent findings are consistent with a model, where salt stress triggers a metabolic shift from fermentation to respiration fueled by the enhanced peroxisomal oxidation of fatty acids. We discuss here the regulatory details of this stress-induced metabolic shift and its possible roles in the context of the previously known adaptive functions.The work of the authors was supported by grants from Ministerio de Economía y Competitividad (BFU2011- 23326 and BFU2016-75792-R).Pascual-Ahuir Giner, MD.; Manzanares-Estreder, S.; Timón Gómez, A.; Proft ., MH. (2017). Ask yeast how to burn your fats: lessons learned from the metabolic adaptation to salt stress. Current Genetics. 64(1):63-69. https://doi.org/10.1007/s00294-017-0724-5S6369641Aguilera J, Prieto JA (2001) The Saccharomyces cerevisiae aldose reductase is implied in the metabolism of methylglyoxal in response to stress conditions. Curr Genet 39:273–283Albertyn J, Hohmann S, Thevelein JM, Prior BA (1994) GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol 14:4135–4144Alepuz PM, Jovanovic A, Reiser V, Ammerer G (2001) Stress-induced map kinase Hog1 is part of transcription activation complexes. Mol Cell 7:767–777Alepuz PM, de Nadal E, Zapater M, Ammerer G, Posas F (2003) Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II. EMBO J 22:2433–2442Ansell R, Granath K, Hohmann S, Thevelein JM, Adler L (1997) The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation. EMBO J 16:2179–2187Babazadeh R, Lahtvee PJ, Adiels CB, Goksor M, Nielsen JB, Hohmann S (2017) The yeast osmostress response is carbon source dependent. Sci Rep 7:990Bender T, Pena G, Martinou JC (2015) Regulation of mitochondrial pyruvate uptake by alternative pyruvate carrier complexes. EMBO J 34:911–924Berry DB, Gasch AP (2008) Stress-activated genomic expression changes serve a preparative role for impending stress in yeast. Mol Biol Cell 19:4580–4587Bilsland-Marchesan E, Arino J, Saito H, Sunnerhagen P, Posas F (2000) Rck2 kinase is a substrate for the osmotic stress-activated mitogen-activated protein kinase Hog1. Mol Cell Biol 20:3887–3895Brewster JL, Gustin MC (2014) Hog 1: 20 years of discovery and impact. Sci Signal 7:re7Clotet J, Posas F (2007) Control of cell cycle in response to osmostress: lessons from yeast. Methods Enzymol 428:63–76Clotet J, Escote X, Adrover MA, Yaakov G, Gari E, Aldea M, de Nadal E, Posas F (2006) Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J 25:2338–2346Cook KE, O’Shea EK (2012) Hog1 controls global reallocation of RNA Pol II upon osmotic shock in Saccharomyces cerevisiae. Genes Genomes Genetics 2:1129–1136de Nadal E, Posas F (2015) Osmostress-induced gene expression—a model to understand how stress-activated protein kinases (SAPKs) regulate transcription. FEBS J 282:3275–3285de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3:735–740de Nadal E, Casadome L, Posas F (2003) Targeting the MEF2-like transcription factor Smp1 by the stress-activated Hog1 mitogen-activated protein kinase. Mol Cell Biol 23:229–237de Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G, Posas F (2004) The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427:370–374Duch A, de Nadal E, Posas F (2013a) Dealing with transcriptional outbursts during S phase to protect genomic integrity. J Mol Biol 425:4745–4755Duch A, Felipe-Abrio I, Barroso S, Yaakov G, Garcia-Rubio M, Aguilera A, de Nadal E, Posas F (2013b) Coordinated control of replication and transcription by a SAPK protects genomic integrity. Nature 493:116–119Escote X, Zapater M, Clotet J, Posas F (2004) Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nat Cell Biol 6:997–1002Ferreira C, van Voorst F, Martins A, Neves L, Oliveira R, Kielland-Brandt MC, Lucas C, Brandt A (2005) A member of the sugar transporter family, Stl1p is the glycerol/H+ symporter in Saccharomyces cerevisiae. Mol Biol Cell 16:2068–2076Gonzalez R, Morales P, Tronchoni J, Cordero-Bueso G, Vaudano E, Quiros M, Novo M, Torres-Perez R, Valero E (2016) New genes involved in osmotic stress tolerance in Saccharomyces cerevisiae. Front Microbiol 7:1545Ho YH, Gasch AP (2015) Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling. Curr Genet 61:503–511Hohmann S (2015) An integrated view on a eukaryotic osmoregulation system. Curr Genet 61:373–382Hohmann S, Krantz M, Nordlander B (2007) Yeast osmoregulation. Methods Enzymol 428:29–45Hong SP, Carlson M (2007) Regulation of snf1 protein kinase in response to environmental stress. J Biol Chem 282:16838–16845Li SC, Diakov TT, Rizzo JM, Kane PM (2012) Vacuolar H+-ATPase works in parallel with the HOG pathway to adapt Saccharomyces cerevisiae cells to osmotic stress. Eukaryot Cell 11:282–291Maeta K, Izawa S, Inoue Y (2005) Methylglyoxal, a metabolite derived from glycolysis, functions as a signal initiator of the high osmolarity glycerol-mitogen-activated protein kinase cascade and calcineurin/Crz1-mediated pathway in Saccharomyces cerevisiae. J Biol Chem 280:253–260Manzanares-Estreder S, Espi-Bardisa J, Alarcon B, Pascual-Ahuir A, Proft M (2017) Multilayered control of peroxisomal activity upon salt stress in Saccharomyces cerevisiae. Mol Microbiol 104:851–868Mao K, Wang K, Zhao M, Xu T, Klionsky DJ (2011) Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J Cell Biol 193:755–767Martinez-Montanes F, Pascual-Ahuir A, Proft M (2010) Toward a genomic view of the gene expression program regulated by osmostress in yeast. OMICS 14:619–627Martinez-Pastor M, Proft M, Pascual-Ahuir A (2010) Adaptive changes of the yeast mitochondrial proteome in response to salt stress. OMICS 14:541–552Mas G, de Nadal E, Dechant R, Rodriguez de la Concepcion ML, Logie C, Jimeno-Gonzalez S, Chavez S, Ammerer G, Posas F (2009) Recruitment of a chromatin remodelling complex by the Hog1 MAP kinase to stress genes. EMBO J 28:326–336Mettetal JT, Muzzey D, Gomez-Uribe C, van Oudenaarden A (2008) The frequency dependence of osmo-adaptation in Saccharomyces cerevisiae. Science 319:482–484Molin C, Jauhiainen A, Warringer J, Nerman O, Sunnerhagen P (2009) mRNA stability changes precede changes in steady-state mRNA amounts during hyperosmotic stress. RNA 15:600–614Nadal-Ribelles M, Conde N, Flores O, Gonzalez-Vallinas J, Eyras E, Orozco M, de Nadal E, Posas F (2012) Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling. Genome Biol 13:R106Pastor MM, Proft M, Pascual-Ahuir A (2009) Mitochondrial function is an inducible determinant of osmotic stress adaptation in yeast. J Biol Chem 284:30307–30317Petelenz-Kurdziel E, Kuehn C, Nordlander B, Klein D, Hong KK, Jacobson T, Dahl P, Schaber J, Nielsen J, Hohmann S, Klipp E (2013) Quantitative analysis of glycerol accumulation, glycolysis and growth under hyper osmotic stress. PLoS Comput Biol 9:e1003084Posas F, Chambers JR, Heyman JA, Hoeffler JP, de Nadal E, Arino J (2000) The transcriptional response of yeast to saline stress. J Biol Chem 275:17249–17255Proft M, Struhl K (2002) Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress. Mol Cell 9:1307–1317Proft M, Struhl K (2004) MAP kinase-mediated stress relief that precedes and regulates the timing of transcriptional induction. Cell 118:351–361Proft M, Pascual-Ahuir A, de Nadal E, Arino J, Serrano R, Posas F (2001) Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress. EMBO J 20:1123–1133Proft M, Mas G, de Nadal E, Vendrell A, Noriega N, Struhl K, Posas F (2006) The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress. Mol Cell 23:241–250Ratnakumar S, Young ET (2010) Snf1 dependence of peroxisomal gene expression is mediated by Adr1. J Biol Chem 285:10703–10714Regot S, de Nadal E, Rodriguez-Navarro S, Gonzalez-Novo A, Perez-Fernandez J, Gadal O, Seisenbacher G, Ammerer G, Posas F (2013) The Hog1 stress-activated protein kinase targets nucleoporins to control mRNA export upon stress. J Biol Chem 288:17384–17398Rep M, Krantz M, Thevelein JM, Hohmann S (2000) The transcriptional response of Saccharomyces cerevisiae to osmotic shock. Hot1p and Msn2p/Msn4p are required for the induction of subsets of high osmolarity glycerol pathway-dependent genes. J Biol Chem 275:8290–8300Rep M, Proft M, Remize F, Tamas M, Serrano R, Thevelein JM, Hohmann S (2001) The Saccharomyces cerevisiae Sko1p transcription factor mediates HOG pathway-dependent osmotic regulation of a set of genes encoding enzymes implicated in protection from oxidative damage. Mol Microbiol 40:1067–1083Rienzo A, Poveda-Huertes D, Aydin S, Buchler NE, Pascual-Ahuir A, Proft M (2015) Different mechanisms confer gradual control and memory at nutrient- and stress-regulated genes in yeast. Mol Cell Biol 35:3669–3683Romero-Santacreu L, Moreno J, Perez-Ortin JE, Alepuz P (2009) Specific and global regulation of mRNA stability during osmotic stress in Saccharomyces cerevisiae. RNA 15:1110–1120Roy A, Hashmi S, Li Z, Dement AD, Cho KH, Kim JH (2016) The glucose metabolite methylglyoxal inhibits expression of the glucose transporter genes by inactivating the cell surface glucose sensors Rgt2 and Snf3 in yeast. Mol Biol Cell 27:862–871Ruiz-Roig C, Noriega N, Duch A, Posas F, de Nadal E (2012) The Hog1 SAPK controls the Rtg1/Rtg3 transcriptional complex activity by multiple regulatory mechanisms. Mol Biol Cell 23:4286–4296Saito H, Posas F (2012) Response to hyperosmotic stress. Genetics 192:289–318Sekito T, Thornton J, Butow RA (2000) Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p. Mol Biol Cell 11:2103–2115Silva RD, Sotoca R, Johansson B, Ludovico P, Sansonetty F, Silva MT, Peinado JM, Corte-Real M (2005) Hyperosmotic stress induces metacaspase- and mitochondria-dependent apoptosis in Saccharomyces cerevisiae. Mol Microbiol 58:824–834Sole C, Nadal-Ribelles M, de Nadal E, Posas F (2015) A novel role for lncRNAs in cell cycle control during stress adaptation. Curr Genet 61:299–308Tamas MJ, Luyten K, Sutherland FC, Hernandez A, Albertyn J, Valadi H, Li H, Prior BA, Kilian SG, Ramos J, Gustafsson L, Thevelein JM, Hohmann S (1999) Fps1p controls the accumulation and release of the compatible solute glycerol in yeast osmoregulation. Mol Microbiol 31:1087–1104Teige M, Scheikl E, Reiser V, Ruis H, Ammerer G (2001) Rck2, a member of the calmodulin-protein kinase family, links protein synthesis to high osmolarity MAP kinase signaling in budding yeast. Proc Natl Acad Sci USA 98:5625–5630Timon-Gomez A, Proft M, Pascual-Ahuir A (2013) Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast. PLoS One 8:e79405Vanacloig-Pedros E, Bets-Plasencia C, Pascual-Ahuir A, Proft M (2015) Coordinated gene regulation in the initial phase of salt stress adaptation. J Biol Chem 290:10163–10175Warringer J, Hult M, Regot S, Posas F, Sunnerhagen P (2010) The HOG pathway dictates the short-term translational response after hyperosmotic shock. Mol Biol Cell 21:3080–3092Wei CJ, Tanner RD, Malaney GW (1982) Effect of sodium chloride on bakers’ yeast growing in gelatin. Appl Environ Microbiol 43:757–763Westfall PJ, Patterson JC, Chen RE, Thorner J (2008) Stress resistance and signal fidelity independent of nuclear MAPK function. Proc Natl Acad Sci USA 105:12212–12217Ye T, Garcia-Salcedo R, Ramos J, Hohmann S (2006) Gis4, a new component of the ion homeostasis system in the yeast Saccharomyces cerevisiae. Eukaryot Cell 5:1611–1621Yoshida A, Wei D, Nomura W, Izawa S, Inoue Y (2012) Reduction of glucose uptake through inhibition of hexose transporters and enhancement of their endocytosis by methylglyoxal in Saccharomyces cerevisiae. J Biol Chem 287:701–71

    Electron affinities of the first- and second- row atoms: benchmark ab initio and density functional calculations

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    A benchmark ab initio and density functional (DFT) study has been carried out on the electron affinities of the first- and second-row atoms. The ab initio study involves basis sets of spdfghspdfgh and spdfghispdfghi quality, extrapolations to the 1-particle basis set limit, and a combination of the CCSD(T), CCSDT, and full CI electron correlation methods. Scalar relativistic and spin-orbit coupling effects were taken into account. On average, the best ab initio results agree to better than 0.001 eV with the most recent experimental results. Correcting for imperfections in the CCSD(T) method improves the mean absolute error by an order of magnitude, while for accurate results on the second-row atoms inclusion of relativistic corrections is essential. The latter are significantly overestimated at the SCF level; for accurate spin-orbit splitting constants of second-row atoms inclusion of (2s,2p) correlation is essential. In the DFT calculations it is found that results for the 1st-row atoms are very sensitive to the exchange functional, while those for second-row atoms are rather more sensitive to the correlation functional. While the LYP correlation functional works best for first-row atoms, its PW91 counterpart appears to be preferable for second-row atoms. Among ``pure DFT'' (nonhybrid) functionals, G96PW91 (Gill 1996 exchange combined with Perdew-Wang 1991 correlation) puts in the best overall performance. The best results overall are obtained with the 1-parameter hybrid modified Perdew-Wang (mPW1) exchange functionals of Adamo and Barone [J. Chem. Phys. {\bf 108}, 664 (1998)], with mPW1LYP yielding the best results for first-row, and mPW1PW91 for second-row atoms. Indications exist that a hybrid of the type aa mPW1LYP + (1a)(1-a) mPW1PW91 yields better results than either of the constituent functionals.Comment: Phys. Rev. A, in press (revised version, review of issues concerning DFT and electron affinities added

    Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID)

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    ObjectiveThe objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. MethodsThe GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud's and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, the investigators rated their patients as non-, partial or complete responders based on clinical grounds. ResultsData from 85 SLE patients were collected, 69 female and 16 male, with a mean disease duration of 9.8 years. The mean follow-up period was 9.67.4 months, resulting in 66.8 patient years of observation. A complete response was reported in 37 patients (46.8%), partial response in 27 (34.2%), no response in 15 (19.0%). On average, major clinical as well as laboratory efficacy parameters improved substantially, with the SLEDAI decreasing significantly from 12.2 to 3.3 points. Concerning safety, one infusion reaction leading to discontinuation of treatment occurred. Infections were reported with a rate of 19.5 (including six severe infections) per 100 patient years. ConclusionWith the restrictions of a retrospective data collection, the results of this study confirm data of other registries, which suggest a favourable benefit-risk ratio of rituximab in patients with treatment-refractory SLE

    Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID)

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    ObjectiveThe objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. MethodsThe GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud's and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, the investigators rated their patients as non-, partial or complete responders based on clinical grounds. ResultsData from 85 SLE patients were collected, 69 female and 16 male, with a mean disease duration of 9.8 years. The mean follow-up period was 9.67.4 months, resulting in 66.8 patient years of observation. A complete response was reported in 37 patients (46.8%), partial response in 27 (34.2%), no response in 15 (19.0%). On average, major clinical as well as laboratory efficacy parameters improved substantially, with the SLEDAI decreasing significantly from 12.2 to 3.3 points. Concerning safety, one infusion reaction leading to discontinuation of treatment occurred. Infections were reported with a rate of 19.5 (including six severe infections) per 100 patient years. ConclusionWith the restrictions of a retrospective data collection, the results of this study confirm data of other registries, which suggest a favourable benefit-risk ratio of rituximab in patients with treatment-refractory SLE

    Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID)

    Get PDF
    Objective The objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. Methods The GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud’s and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, the investigators rated their patients as non-, partial or complete responders based on clinical grounds. Results Data from 85 SLE patients were collected, 69 female and 16 male, with a mean disease duration of 9.8 years. The mean follow-up period was 9.6 ± 7.4 months, resulting in 66.8 patient years of observation. A complete response was reported in 37 patients (46.8%), partial response in 27 (34.2%), no response in 15 (19.0%). On average, major clinical as well as laboratory efficacy parameters improved substantially, with the SLEDAI decreasing significantly from 12.2 to 3.3 points. Concerning safety, one infusion reaction leading to discontinuation of treatment occurred. Infections were reported with a rate of 19.5 (including six severe infections) per 100 patient years. Conclusion With the restrictions of a retrospective data collection, the results of this study confirm data of other registries, which suggest a favourable benefit-risk ratio of rituximab in patients with treatment-refractory SLE
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