Direct and Indirect Effects of Cytomegalovirus-Induced γδ T Cells after Kidney Transplantation

Despite effective anti-viral therapies, cytomegalovirus (CMV) is still associated with direct (CMV disease) and indirect effects (rejection and poor graft survival) in kidney transplant recipients. Recently, an unconventional T cell population (collectively designated as Vδ2neg γδ T cells) has been characterized during the anti-CMV immune response in all solid-organ and bone-marrow transplant recipients, neonates, and healthy people. These CMV-induced γδ T cells undergo a dramatic and stable expansion after CMV infection, in a conventional ‘adaptive’ manner. Similarly as CMV-specific CD8+ αβ T cells, they exhibit an effector/memory TEMRA phenotype and cytotoxic effector functions. Activation of Vd2neg gd T cells by CMV-infected cells involves the TCR and still ill-defined co-stimulatory molecules such LFA-1. A multiple of Vd2neg gd TCR ligands are apparently recognized on CMV-infected cells, the first one identified being the MHC-related molecule endothelial protein C receptor (EPCR). A singularity of CMV-induced Vd2neg gd T cells is to acquire CD16 expression and to exert an antibody-dependent cell-mediated inhibition on CMV replication, which is controlled by a specific cytokine microenvironment. Beyond the well-demonstrated direct anti-CMV effect of Vδ2neg γδ T cells, unexpected indirect effects of these cells have been also observed in the context of kidney transplantation. CMV-induced Vδ2neg γδ T cells have been involved in surveillance of malignancy subsequent to long term immunosuppression. Moreover, CMV-induced CD16+ γδ T cells are cell effectors of antibody-mediated rejection of kidney transplants, and represent a new physiopathological contribution to the well-known association between CMV infection and poor graft survival. All these basic and clinical studies paved the road to the development of a future γδ T cell-based immunotherapy. In the meantime, γδ T cell monitoring should prove a valuable immunological biomarker in the management of CMV infection

Reduced parathyroid functional mass after successful kidney transplantation

Reduced parathyroid functional mass after successful kidney transplantation.BackgroundChronic uremia is responsible for secondary hyperparathyroidism (HPT II). Parathyroid secretion usually tends to normalize after kidney transplantation (KT), but the parameters of the reversibility of HPT II remain poorly defined, particularly the intrinsic mechanisms underlying the improvement of parathyroid function.MethodsThe kinetic functional parameters of the ionized calcium (iCa)/parathormone (PTH) relationship curve were studied in 11 patients with mild to moderate HPT II one and six months after successful KT. Hypercalcemia and hypocalcemia were induced, respectively, by CaCl2 and Na2-ethylenediaminetetraacetic acid (Na2-EDTA) infusions.ResultsThe mean glomerular filtration rate remained stable during follow-up. Basal PTH decreased from 195 ± 54 pg/ml before KT to 70 ± 12 pg/ml six months later (P < 0.005). During the tests, mean PTH levels decreased significantly between the two measured times for all iCa levels, indicating an improved parathyroid function. An analysis of the kinetic parameters of the curves showed significant decreases of the mean maximal and minimal PTH levels, respectively, from 340 ± 91 to 220 ± 30 pg/ml (P = 0.03) and from 25 ± 6 to 15 ± 5 pg/ml (P = 0.005). On the other hand, no change was noted in the parathyroid-cell calcium-sensitivity parameters (slope, set point) assessed using two different approaches, either the entire curve or the limited calcium-mediated suppression curve.ConclusionImprovement of the parathyroid function between the first and sixth months post-KT seems mainly attributable to a reduction of the parathyroid functional mass

BMC Nephrol

An amendment to this paper has been published and can be accessed via the original article

Women in Brussels street names. Topography of a minoritisation

The article proposes an examination of odonyms in Brussels, i.e. the names of its streets, through the prism of gender. After a systematic survey of street names and the characteristics of the female figures honoured – which reveals a glaring imbalance between the female and male street names in Brussels (there are ten times fewer female odonyms than male odonyms in the Region) – the article analyses the practices and strategies used by municipal representatives to feminise street names and do justice to the memory of women through a transformation of the toponymy, among other things. On the one hand, it reveals the constraints linked to legislation, urban morphology and gender stereotypes which weigh on the undertaking to increase the number of female street names and, on the other hand, it analyses the action of elected representatives and the influence of feminist organisations which fight against the minoritisation of women in the materiality of the Brussels urban space.L’article propose un examen de l’odonymie de Bruxelles, c’est-à-dire des dénominations de ses voiries, sous le prisme du genre. Après un relevé systématique du nom des rues et des caractéristiques des figures féminines mises en valeur, qui révèle un déséquilibre criant entre les noms féminins et masculins des rues de Bruxelles (sur l’ensemble de la Région, on compte dix fois moins d’odonymes féminins que masculins), l’article analyse les pratiques et les stratégies déployées par les élu∙e∙s à l’échelle communale pour féminiser le nom des rues et rendre justice à la mémoire des femmes à travers une transformation de la toponymie, entre autres. D’une part, il dévoile les contraintes liées à la législation, à la morphologie urbaine ou aux stéréotypes genrés qui pèsent sur l’entreprise d’accroissement du nombre de noms de rues féminins et, d’autre part, il analyse l’action des élu∙e∙s et l’influence des organisations féministes qui luttent contre la minorisation des femmes dans la matérialité de l’espace urbain bruxellois.Het artikel onderzoekt de Brusselse straatnaamgeving vanuit genderoogpunt. Na een systematisch overzicht van de straatnamen en van de kenmerken van de vrouwelijke figuren in straatnamen, waaruit een overduidelijke wanverhouding tussen het gebruik van vrouwen- en mannennamen in Brusselse straatnamen (in het hele Gewest zijn er tien keer minder vrouwelijke straatnamen dan mannelijke) blijkt, onderzoekt het artikel de praktijken en de strategieën van verkozenen op gemeentelijk niveau om straatnamen te vervrouwelijken en om de nagedachtenis van vrouwen eer aan te doen door onder andere de toponymie te herzien. Enerzijds wijst het artikel op de beperkingen die verband houden met de wetgeving, stadsmorfologie of genderstereotypen en die het moeilijk maken om het aantal vrouwelijke straatnamen te verhogen. Anderzijds analyseert het de inspanningen van verkozenen en de invloed van vrouwenorganisaties die de strijd aanbinden tegen de minorisering van vrouwen in de materialiteit van de Brusselse stadsruimte

Vrouwen in Brusselse straatnamen. Topografie van een minorisering

Het artikel onderzoekt de Brusselse straatnaamgeving vanuit genderoogpunt. Na een systematisch overzicht van de straatnamen en van de kenmerken van de vrouwelijke figuren in straatnamen, waaruit een overduidelijke wanverhouding tussen het gebruik van vrouwen- en mannennamen in Brusselse straatnamen (in het hele Gewest zijn er tien keer minder vrouwelijke straatnamen dan mannelijke) blijkt, onderzoekt het artikel de praktijken en de strategieën van verkozenen op gemeentelijk niveau om straatnamen te vervrouwelijken en om de nagedachtenis van vrouwen eer aan te doen door onder andere de toponymie te herzien. Enerzijds wijst het artikel op de beperkingen die verband houden met de wetgeving, stadsmorfologie of genderstereotypen en die het moeilijk maken om het aantal vrouwelijke straatnamen te verhogen. Anderzijds analyseert het de inspanningen van verkozenen en de invloed van vrouwenorganisaties die de strijd aanbinden tegen de minorisering van vrouwen in de materialiteit van de Brusselse stadsruimte.L’article propose un examen de l’odonymie de Bruxelles, c’est-à-dire des dénominations de ses voiries, sous le prisme du genre. Après un relevé systématique du nom des rues et des caractéristiques des figures féminines mises en valeur, qui révèle un déséquilibre criant entre les noms féminins et masculins des rues de Bruxelles (sur l’ensemble de la Région, on compte dix fois moins d’odonymes féminins que masculins), l’article analyse les pratiques et les stratégies déployées par les élu∙e∙s à l’échelle communale pour féminiser le nom des rues et rendre justice à la mémoire des femmes à travers une transformation de la toponymie, entre autres. D’une part, il dévoile les contraintes liées à la législation, à la morphologie urbaine ou aux stéréotypes genrés qui pèsent sur l’entreprise d’accroissement du nombre de noms de rues féminins et, d’autre part, il analyse l’action des élu∙e∙s et l’influence des organisations féministes qui luttent contre la minorisation des femmes dans la matérialité de l’espace urbain bruxellois.The article proposes an examination of odonyms in Brussels, i.e. the names of its streets, through the prism of gender. After a systematic survey of street names and the characteristics of the female figures honoured – which reveals a glaring imbalance between the female and male street names in Brussels (there are ten times fewer female odonyms than male odonyms in the Region) – the article analyses the practices and strategies used by municipal representatives to feminise street names and do justice to the memory of women through a transformation of the toponymy, among other things. On the one hand, it reveals the constraints linked to legislation, urban morphology and gender stereotypes which weigh on the undertaking to increase the number of female street names and, on the other hand, it analyses the action of elected representatives and the influence of feminist organisations which fight against the minoritisation of women in the materiality of the Brussels urban space

Les femmes dans le nom des rues bruxelloises. Topographie d’une minorisation

L’article propose un examen de l’odonymie de Bruxelles, c’est-à-dire des dénominations de ses voiries, sous le prisme du genre. Après un relevé systématique du nom des rues et des caractéristiques des figures féminines mises en valeur, qui révèle un déséquilibre criant entre les noms féminins et masculins des rues de Bruxelles (sur l’ensemble de la Région, on compte dix fois moins d’odonymes féminins que masculins), l’article analyse les pratiques et les stratégies déployées par les élu∙e∙s à l’échelle communale pour féminiser le nom des rues et rendre justice à la mémoire des femmes à travers une transformation de la toponymie, entre autres. D’une part, il dévoile les contraintes liées à la législation, à la morphologie urbaine ou aux stéréotypes genrés qui pèsent sur l’entreprise d’accroissement du nombre de noms de rues féminins et, d’autre part, il analyse l’action des élu∙e∙s et l’influence des organisations féministes qui luttent contre la minorisation des femmes dans la matérialité de l’espace urbain bruxellois.Het artikel onderzoekt de Brusselse straatnaamgeving vanuit genderoogpunt. Na een systematisch overzicht van de straatnamen en van de kenmerken van de vrouwelijke figuren in straatnamen, waaruit een overduidelijke wanverhouding tussen het gebruik van vrouwen- en mannennamen in Brusselse straatnamen (in het hele Gewest zijn er tien keer minder vrouwelijke straatnamen dan mannelijke) blijkt, onderzoekt het artikel de praktijken en de strategieën van verkozenen op gemeentelijk niveau om straatnamen te vervrouwelijken en om de nagedachtenis van vrouwen eer aan te doen door onder andere de toponymie te herzien. Enerzijds wijst het artikel op de beperkingen die verband houden met de wetgeving, stadsmorfologie of genderstereotypen en die het moeilijk maken om het aantal vrouwelijke straatnamen te verhogen. Anderzijds analyseert het de inspanningen van verkozenen en de invloed van vrouwenorganisaties die de strijd aanbinden tegen de minorisering van vrouwen in de materialiteit van de Brusselse stadsruimte.The article proposes an examination of odonyms in Brussels, i.e. the names of its streets, through the prism of gender. After a systematic survey of street names and the characteristics of the female figures honoured – which reveals a glaring imbalance between the female and male street names in Brussels (there are ten times fewer female odonyms than male odonyms in the Region) – the article analyses the practices and strategies used by municipal representatives to feminise street names and do justice to the memory of women through a transformation of the toponymy, among other things. On the one hand, it reveals the constraints linked to legislation, urban morphology and gender stereotypes which weigh on the undertaking to increase the number of female street names and, on the other hand, it analyses the action of elected representatives and the influence of feminist organisations which fight against the minoritisation of women in the materiality of the Brussels urban space

Proteomic mass spectra classification using decision tree based ensemble methods.

MOTIVATION: Modern mass spectrometry allows the determination of proteomic fingerprints of body fluids like serum, saliva or urine. These measurements can be used in many medical applications in order to diagnose the current state or predict the evolution of a disease. Recent developments in machine learning allow one to exploit such datasets, characterized by small numbers of very high-dimensional samples. RESULTS: We propose a systematic approach based on decision tree ensemble methods, which is used to automatically determine proteomic biomarkers and predictive models. The approach is validated on two datasets of surface-enhanced laser desorption/ionization time of flight measurements, for the diagnosis of rheumatoid arthritis and inflammatory bowel diseases. The results suggest that the methodology can handle a broad class of similar problems

High Risk of Acute Kidney Failure in Kidney Transplant Recipients Early after Bariatric Surgery

Bariatric surgery is routinely proposed to patients suffering from obesity including kidney transplant recipients. In this specific population, bariatric surgery has a positive impact in long-term outcomes in terms of patient and graft survival. We report here the cases of 4 patients with five post-kidney transplantation bariatric surgeries who experimented acute renal injury early after surgery. Creatinine rising occurred between day 14 and day 20 after surgery. In all cases, it was due to dehydration leading to a pre-renal acute renal failure. The specific care of kidney transplanted patients is discussed: single kidney associated with pre-existing altered kidney function associated with concomitant use of nephrotoxic drugs. Specific education intervention before surgery associated with careful early management of hydration after surgery is mandatory for these patients

Biomedicines

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest

Discovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ProteinChip approach.

peer reviewedOBJECTIVE: To identify serum protein biomarkers specific for rheumatoid arthritis (RA), using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. METHODS: A total of 103 serum samples from patients and healthy controls were analyzed. Thirty-four of the patients had a diagnosis of RA, based on the American College of Rheumatology criteria. The inflammation control group comprised 20 patients with psoriatic arthritis (PsA), 9 with asthma, and 10 with Crohn's disease. The noninflammation control group comprised 14 patients with knee osteoarthritis and 16 healthy control subjects. Serum protein profiles were obtained by SELDI-TOF-MS and compared in order to identify new biomarkers specific for RA. Data were analyzed by a machine learning algorithm called decision tree boosting, according to different preprocessing steps. RESULTS: The most discriminative mass/charge (m/z) values serving as potential biomarkers for RA were identified on arrays for both patients with RA versus controls and patients with RA versus patients with PsA. From among several candidates, the following peaks were highlighted: m/z values of 2,924 (RA versus controls on H4 arrays), 10,832 and 11,632 (RA versus controls on CM10 arrays), 4,824 (RA versus PsA on H4 arrays), and 4,666 (RA versus PsA on CM10 arrays). Positive results of proteomic analysis were associated with positive results of the anti-cyclic citrullinated peptide test. Our observations suggested that the 10,832 peak could represent myeloid-related protein 8. CONCLUSION: SELDI-TOF-MS technology allows rapid analysis of many serum samples, and use of decision tree boosting analysis as the main statistical method allowed us to propose a pattern of protein peaks specific for RA