126 research outputs found
Unrecognized sequence homologies may confound genome-wide association studies
Genome-wide association studies (GWAS) have become a preferred method to identify new genetic susceptibility loci. This technique aims to understanding the molecular etiology of common diseases, but in many cases, it has led to the identification of loci with no obvious biological relevance. Herein, we show that previously unrecognized sequence homologies have caused single-nucleotide polymorphism (SNP) microarrays to incorrectly associate a phenotype to a given locus when in fact the linkage is to another distant locus. Using genetic differences between male and female subjects as a model to study the effect of one specific genomic region on the whole SNP microarray, we provide strong evidence that the use of standard methods for GWAS can be misleading. We suggest a new systematic quality control step in the biological interpretation of previous and future GWAS
The Ets-1 transcription factor controls the development and function of natural regulatory T cells
Regulatory T cells (T reg cells) constitute a population of CD4+ T cells that limits immune responses. The transcription factor Foxp3 is important for determining the development and function of T reg cells; however, the molecular mechanisms that trigger and maintain its expression remain incompletely understood. In this study, we show that mice deficient for the Ets-1 transcription factor (Ets-1â/â) developed T cellâmediated splenomegaly and systemic autoimmunity that can be blocked by functional wild-type T reg cells. Spleens of Ets-1â/â mice contained mostly activated T cells, including Th2-polarized CD4+ cells and had reduced percentages of T reg cells. Splenic and thymic Ets-1â/â T reg cells expressed low levels of Foxp3 and displayed the CD103 marker that characterizes antigen-experienced T reg cells. Thymic development of Ets-1â/â T reg cells appeared intrinsically altered as Foxp3-expressing cells differentiate poorly in mixed fetal liver reconstituted chimera and fetal thymic organ culture. Ets-1â/â T reg cells showed decreased in vitro suppression activity and did not protect Rag2â/â hosts from naive T cellâinduced inflammatory bowel disease. Furthermore, in T reg cells, Ets-1 interacted with the Foxp3 intronic enhancer and was required for demethylation of this regulatory sequence. These data demonstrate that Ets-1 is required for the development of natural T reg cells and suggest a role for this transcription factor in the regulation of Foxp3 expression
Race-free estimated glomerular filtration rate equation in kidney transplant recipients:development and validation study
OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).PARTICIPANTS: 15â489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11â867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15â489 participants, with 50â464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.</p
Pathogénie de la glomérulonéphrite expérimentale par anticorps anti membrane basale glomérulaire chez la souris (rÎle des cellules INKT, de la vitronectine et du fond génétique)
PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF
Influence de la transplantation rénale sur la rigidité aortique au cours de la premiÚre année post greffe (étude d'une cohorte de 50 patients)
PARIS6-Bibl.PitiĂ©-SalpĂȘtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Red urine, updated for the nephrologist: a case report
International audienceBackgroundSickle cell trait is not completely benign, and some renal complications can occur. The baseline rate of admission for gross hematuria in normal males carrying the sickle cell trait is 2%.Case presentationA 35-year-old non-smoking African man experienced a 2-week history of painless, profuse and persistent gross hematuria. Laboratory tests showed normal renal function, hematuria and mild proteinuria. Abdominal ultrasonography and computed tomography angiography revealed no renal abnormalities; the bladder appeared pristine under cystoscopy. The diagnosis of sickle cell trait associated with gross hematuria was made using hemoglobin electrophoresis; renal biopsy and its complications were avoided. Urine was clear after 2 weeks of oral hydration and gamma epsilon-aminocaproic acid.ConclusionHemoglobin electrophoresis should be performed in cases of gross hematuria. Coupled with other non-invasive evaluation, this could avoid renal biopsy and its associated complications
Autoantibodies specific for the phospholipase A2 receptor in recurrent andâDe Novoâmembranous nephropathy.
International audienceRecent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent andâde novoâMN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients withâde novoâMN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies
Varia
La prĂ©sente livraison du Courrier du Centre International Blaise Pascal reprend la formule du numĂ©ro 16, en proposant aux amis de Pascal les actes de la journĂ©e de travail sur Les Provinciales Ă Clermont par le CIBP, avec lâaide de son UniversitĂ© de tutelle. Le compte rendu en a Ă©tĂ© donnĂ© dans notre prĂ©cĂ©dent numĂ©ro par Catherine Favereau, qui prĂ©pare actuellement une thĂšse de doctorat de stylistique pascalienne. Je nâajouterai donc rien sur la substance de cette journĂ©e, qui a laissĂ© un bon souvenir de travail efficace. Deux regrets ont tempĂ©rĂ© la satisfaction des participants, lâabsence dâun homme, notre ami GĂ©rard Ferreyrolles qui nâavait pu se dĂ©gager de ses lourdes obligations professionnelles, et celle dâun livre, puisque le tome 5 des Ćuvres complĂštes de Pascal Ă©ditĂ©es par Jean Mesnard, qui devait justement contenir les Provinciales, nâa pas pu paraĂźtre Ă temps pour transformer la journĂ©e de travail en cĂ©lĂ©bration pascalienne. Ce sera pour une autre fois. Heureusement, Ă dĂ©faut de lâĂ©dition, nous avions lâĂ©diteur. Comme directeur du CIBP, je souhaite souligner lâefficacitĂ© de la formule des journĂ©es de travail telles que nous les avons rĂ©alisĂ©es sur les PensĂ©es, les trois ordres, Antoine Arnauld et Les Provinciales. BrĂšves mais intenses, elles permettent de faire le point au cours dâune rĂ©flexion commune dense, mettant en contact des chercheurs confirmĂ©s avec des Ă©tudiants Ă vocation pascalienne ou simplement attirĂ©s par les nĂ©cessitĂ©s du programme universitaire. Le rĂ©sultat en est toujours solide : on sâen assurera en lisant le volume Ă©ditĂ© par notre ami Jean-Claude Pariente sur Antoine Arnauld Ă la librairie philosophique Vrin, qui concrĂ©tise lâun des objectifs majeurs du CIBP, lâextension de ses relations au monde des spĂ©cialistes de la philosophie. La journĂ©e sur les trois ordres sera sans doute publiĂ©e prochainement par les soins de Martine PĂ©charman-Petit dans une revue philosophique. Enfin, la prĂ©sente livraison permettra Ă nos amis de trouver le dernier Ă©tat des travaux sur les Provinciales
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