No evidence of association between genetic variants of the PDCD1 ligands and SLE

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.Genes and Immunity (2007) 8, 69-74. doi:10.1038/sj.gene.6364360; published online 30 November 2006

Remission or low disease activity as a target in systemic lupus erythematosus.

Se comenta un estudio sobre el estado de baja actividad de la enfermedad del lupus está asociado con la disminución de la progresión del daño en pacientes caucásicos con Lupus Eritematoso Sistémico

Етнологія релігії – актуальна сфера українського релігієзнавства

Background: Inhaled long-acting beta-2-adrenoceptor agonists (LABA) are frequently used in patients suffering from asthma and chronic obstructive pulmonary disease (COPD). For evaluation of real-life data, drug consumption studies are needed but results might be widely influenced due to methodological differences in particular regarding inter-country comparisons. Objectives: This study aims to compare the LABA prescribing in the general population and specifically in patients suffering from asthma and/or COPD in five European countries. Methods: Crude and age- and sex-standardized (European 2008 reference population) annual period prevalence rates per 10,000 persons were calculated for the period 2002-2009 based on seven European electronic health record databases (Denmark, Germany, Spain, the Netherlands (2), and the United Kingdom (2)). Stratification by sex, age, and indication were performed for the annual period prevalence rates. Results: In all databases, we observed an increase in LABA prescriptions during the study period for the general population and for patients suffering from asthma and/or COPD. In 2008, the highest standardized period prevalence was observed in the Dutch Mondriaan-AHC and the Spanish BIFAP database (443.3 and 395.5 per 10,000 persons), and the lowest in the German Bavarian Claims and Dutch Mondriaan- NPRCD database (278.7 and 290.6 per 10,000 persons). Prevalence rates for LABA increased with age and were highest in patients over 70 years. Patients with a combined diagnosis of asthma and COPD had higher prevalence rates of LABA compared to patients with a single diagnosis of asthma or COPD. The proportion of patients with one inhaled LABA prescription only ranged from 14% (UK databases) to 35% (Spanish BIFAP database) in 2008 in the general population. Conclusions: By using a standardized protocol, we demonstrated inter- and intra-country differences in LABA prescriptions. A general increase of LABA prescriptions during the study period was observed in all databases

An Open, Large-Scale, Collaborative Effort to Estimate the Reproducibility of Psychological Science

Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. So far, 72 volunteer researchers from 41 institutions have organized to openly and transparently replicate studies published in three prominent psychological journals in 2008. Multiple methods will be used to evaluate the findings, calculate an empirical rate of replication, and investigate factors that predict reproducibility. Whatever the result, a better understanding of reproducibility will ultimately improve confidence in scientific methodology and findings

Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans

Spatial variation in determinants of agricultural land abandonment in Europe

© 2018 Elsevier B.V. Agricultural abandonment is widespread and growing in many regions worldwide, often because of agricultural intensification on productive lands, conservation policies, or the spatial decoupling of agricultural production from consumption. Abandonment has major environmental and social impacts, which differ starkly depending on the geographical context, as does its potential to serve as a land reservoir for recultivation. Understanding determinants of abandonment patterns, and especially how their influence varies across broad geographic extents, is therefore important. Using a pan-European map of agricultural abandonment derived from MODIS NDVI time series between 2001 and 2012, we quantified the importance of farm management, climatic, environmental, and socio-economic variables in explaining abandonment patterns. We chose a machine learning modelling framework that accounts for spatial variation in the relationship between abandonment and its determinants. We predicted abandonment probability as well as determinant coefficients for the entire study area and summarised them for regions under selected EU support schemes. Our results highlight that agricultural abandonment was mainly explained by climate conditions suboptimal for agriculture (i.e., low/high growing degrees days). Determinants related to farm management (smaller field size, lower yields) and socio-economic conditions (high unemployment, negative migration balance) also contributed to describing agricultural abandonment patterns in Europe. Several determinants influenced abandonment in strongly non-linear ways and we found substantial spatial non-stationarity effects, although abandonment patterns were equally well-explained by predictors specified with spatially constant and varying effects. Predicted abandonment probability was similar inside and outside EU support or conservation zones, whereas observed MODIS-based abandonment was generally higher outside these zones, suggesting that schemes such as Natura 2000 or High Nature Value Farmland likely influence abandonment patterns. Our work highlights the potential value of spatial boosting for gaining insights into land-use change processes and their outcomes, which should increase the ability of such models to inform context-specific, regionalised decision making

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus : Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)–Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an ’overarching’ treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings