Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: The RH blood group system has many RHCE variant alleles that have arisen through gene conversion or nucleotide changes. Two probands, with red blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to resolve the weak c expression. STUDY DESIGN AND METHODS: Hemagglutination tests were performed by automated and manual procedures. Genomic DNA analysis was performed by sequencing of Exons 1 to 10 of RHCE and RHD. RESULTS: The probands' RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad, Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the presence of C/G at Position 676 (E/e polymorphism) and the association of the E polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro amino acid substitution in the mature RhcE polypeptide. Replacement of leucine 245 by proline in the eighth transmembrane domain of the RhcE protein may have a steric effect on the protein such that most anti-E reagents do not bind and the interaction between anti-c and c antigen is also affected. CONCLUSION: We report a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had weakened c expression and typed E- with conventional anti-E reagents. These data, once again, highlight the fact that the genotype does not always reflect the phenotype.
ISSN: 0041-1132

hal-00839022
https://hal.archives-ouvertes.fr/hal-00839022
DOI : 10.1111/j.1537-2995.2012.03860.x
PUBMED : 22958092

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Cancer is the main complication of transplantation surgery. The literature concerning renal transplant recipients among the Afro-Caribbean population is scant. The aim of this study was to determine the incidence of cancer in these patients, with the secondary objective being to identify predisposing factors for cancer. This was an epidemiological and retrospective study that included all Guadeloupians of phototype V-VI undergoing renal transplantation from 01/01/2004 to 31/12/2011. Skin cancer screening was performed before transplantation and during an annual dermatological consultation following transplantation. Screening for non-cutaneous cancers was guided by clinical symptoms or by the results of the screening examinations recommended in the current guidelines. At the study time-point (31/12/2011), all patients were examined by a dermatologist. One hundred and two patients were included : 42 women and 60 men (mean age: 52.1±11.6 years at transplantation). Eight cancers were diagnosed. The cumulative incidence of cancer was 7.8% at 3 years. Three factors were associated with more rapid onset of cancer: personal history or familial history of cancer, and genital lesion induced by HPV. Our results suggest a low incidence of cancer in Afro-Caribbean renal transplant patients. Personal or family history of cancer and HPV-induced genital lesions would appear to accelerate the onset of cancer in this population.
ISSN: 0151-9638

hal-01260468
https://hal.archives-ouvertes.fr/hal-01260468
https://hal.archives-ouvertes.fr/hal-01260468/document
https://hal.archives-ouvertes.fr/hal-01260468/file/2015%2C%20Ameline.pdf
https://hal.archives-ouvertes.fr/hal-01260468/file/14%20148%20Fig%201%20ap.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0140-6736

hal-01632370
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01632370
DOI : 10.1016/S0140-6736(17)32419-4
PUBMED : 29082874

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B
Résumé : International audience
AIMS: Indications for surgery in acute infective endocarditis (IE) are detailed in guidelines, but their application is not well known. We analysed the agreement between the patient's attending physicians and European Society of Cardiology guidelines regarding indications for surgery. We also assessed whether surgery was performed in patients who had an indication. METHODS AND RESULTS: From the 2008 prospective population-based French survey on IE, 303 patients with definite left-sided native IE were identified. For each case, we prospectively recorded (i) indication for surgery according to the attending physicians and (ii) indication for surgery according to guidelines. Surgery was indicated in 194 (65%) patients according to attending physicians and in 221 (73%) according to guidelines, while 139 (46%) underwent surgery. Agreement was moderate between attending physicians and guidelines (kappa 0.41-0.59) and between indication according to guidelines and the performance of surgery (kappa 0.38). Of the 90 (30%) patients not operated despite indication, contraindication to surgery was reported by the attending physicians in 42 (47%), and indication was not identified in 48 (53%). One-year survival was 76% in patients with indication and surgery performed (n = 131), 69% in patients without indication and no surgery (n = 74), 56% in patients with identified indication and contraindication to surgery (n = 42), and 60% in patients with no identified indication (n = 48; P = 0.059). CONCLUSION: Cardiac surgery during acute IE was recommended in almost three out of four patients, although fewer than half were actually operated. Indication was not acknowledged by the attending physicians in one out of six patients
ISSN: 0195-668X

hal-01255874
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01255874
DOI : 10.1093/eurheartj/ehv650
PUBMED : 26685134

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
The aim of this study was to investigate the role of socioeconomic and healthcare use characteristics in the participation in breast, cervical and colorectal cancer screening in the French West Indies. We used data from a national health survey conducted in 2014 in Martinique (n=2026) and Guadeloupe (n=2028). Logistic regressions adjusted for various sociodemographic and morbidity variables were performed. The following determinants were investigated: having hot water at home, having received income support for low-income individuals during the last year, educational level, occupational class, complementary health insurance, healthcare renouncement and visit to the general practitioner (GP) during the last year. Multiple imputations were performed to account for missing values. We observed the following cancer screening rates: 78.1% for cervical cancer, 81.5% for breast cancer and 59.5% (women) and 50.8% (men) for colorectal cancer. Higher cervical cancer screening participation was reported among women with qualified occupation and having visited the GP during the last year and lower participation among women who never worked. Higher screening participation was reported among participants having hot water at home and having visited the GP during the last year for breast and colorectal (men and women) cancer. Unexpectedly, a lower colorectal cancer screening participation was found among women with qualified occupation. We observed social inequalities in participation in cancer screening in the French West Indies, which stresses the need to continue efforts to increase screening rates in this population.
ISSN: 0959-8278

hal-01525894
http://hal.upmc.fr/hal-01525894
http://hal.upmc.fr/hal-01525894/document
http://hal.upmc.fr/hal-01525894/file/Menvielle_2016_Socioeconomic_and.pdf
DOI : 10.1097/CEJ.0000000000000329

Éditeur(s) : HAL CCSD
Résumé : International audience
Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.
European Respiratory Journal

hal-01647080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647080
DOI : 10.1183/13993003.00716-2017
PUBMED : 29074543

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0360-5442

hal-01654082
https://hal.inria.fr/hal-01654082
DOI : 10.1016/j.energy.2016.06.004

Éditeur(s) : HAL CCSD John Libbey Eurotext
Résumé : National audience
ISSN: 1635-0421

hal-01118600
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118600
DOI : 10.1684/ers.2014.0751

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Background We conducted this systematic review and meta-analysis to address the open question of a possible association between the socioeconomic level of the neighborhoods in which pregnant women live and the risk of Congenital Heart Defects (CHDs), Neural Tube Defects (NTDs) and OroFacial Clefts (OFCs). Methods We searched MEDLINE from its inception to December 20th, 2015 for case-control, cohort and ecological studies assessing the association between neighborhood socioeconomic level and the risk of CHDs, NTDs and the specific phenotypes Cleft Lip with or without Cleft Palate (CLP) and Cleft Palate (CP). Study-specific risk estimates were pooled according to random-effect and fixed-effect models. Results Out of 245 references, a total of seven case-control studies, two cohort studies and two ecological studies were assessed in the systematic review; all studies were enrolled in the meta-analysis with the exception of the two cohort studies. No significant association has been revealed between CHDs or NTDs and neighborhood deprivation index. For CLP phenotype subgroups, we found a significantly higher rate in deprived neighborhoods (Odds Ratios (OR) = 1.22, 95% CI: 1.10, 1.36) whereas this was not significant for CP phenotype subgroups (OR = 1.20, 95%CI: 0.89, 1.61). Conclusion In spite of the small number of epidemiological studies included in the present literature review, our findings suggest that neighborhood socioeconomic level where mothers live is associated only with an increased risk of CLP phenotype subgroups. This finding has methodological limitations that impede the formulation of firm conclusions, and further investigations should confirm this association. © 2016 Deguen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN: 1932-6203

hal-01406070
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01406070
DOI : 10.1371/journal.pone.0159039
PUBMED : 27783616

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a human carcinogen according to the International Agency for Research on Cancer. In addition to triggering apoptotic signals, B[a]P may induce survival signals, both of which are likely to be involved in cancer promotion. We previously suggested that B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell survival signaling in rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing on energy metabolism. We found that B[a]P promoted a metabolic reprogramming. Cell respiration decreased and lactate production increased. These changes were associated with alterations in the tricarboxylic acid cycle which likely involve a dysfunction of the mitochondrial complex II. The glycolytic shift relied on activation of the Na+/H+ exchanger 1 (NHE1) and appeared to be a key feature in B[a]P-induced cell survival related to changes in cell phenotype (epithelial-to-mesenchymal transition and cell migration).
ISSN: 2045-2322

Droits : http://creativecommons.org/licenses/by/
hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/file/The%20environmental%20carcinogen-CCBY%20%281%29.pdf
DOI : 10.1038/srep30776

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Chaperone synthesis in response to proteotoxic stress is dependent on a family of transcription factors named heat shock factors (HSFs). The two main factors in this family, HSF1 and HSF2, are co-expressed in numerous tissues where they can interact and form heterotrimers in response to proteasome inhibition. HSF1 and HSF2 exhibit two alternative splicing isoforms, called α and β, which contribute to additional complexity in HSF transcriptional regulation, but remain poorly examined in the literature. In this work, we studied the transcriptional activity of HSF1 and HSF2 splicing isoforms transfected into immortalized Mouse Embryonic Fibroblasts (iMEFs) deleted for both Hsf1 and Hsf2, under normal conditions and after proteasome inhibition. We found that HSF1α is significantly more active than the β isoform after exposure to the proteasome inhibitor MG132. Furthermore, we clearly established that, while HSF2 had no transcriptional activity by itself, short β isoform of HSF2 exerts a negative role on HSF1β-dependent transactivation. To further assess the impact of HSF2β inhibition on HSF1 activity, we developed a mathematical modelling approach which revealed that the balance between each HSF isoform in the cell regulated the strength of the transcriptional response. Moreover, we found that cellular stress such as proteasome inhibition could regulate the splicing of Hsf2 mRNA. All together, our results suggest that relative amounts of each HSF1 and HSF2 isoforms quantitatively determine the cellular level of the proteotoxic stress response.
ISSN: 1932-6203

inserm-00814784
http://www.hal.inserm.fr/inserm-00814784
http://www.hal.inserm.fr/inserm-00814784/document
http://www.hal.inserm.fr/inserm-00814784/file/journal.pone.0056085.pdf
DOI : 10.1371/journal.pone.0056085

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: In immunocompromised patients, alternative schedules more immunogenic than the standard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy. We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults. This study reports the long-term persistence of the immune response. DESIGN AND METHODS: In a prospective, multicenter, randomized, patient-blinded trial, two doses of AS03A-adjuvanted H1N1v vaccine containing 3.75 μg haemagglutinin (n = 155; group A) or nonadjuvanted H1N1v vaccine containing 15 μg haemagglutinin (n = 151; group B), were administered 21 days apart. Haemagglutination inhibition and neutralizing antibodies were assessed 6 and 12 months after vaccination. RESULTS: In group A and B, the seroprotection rates were 83.7 and 59.4% at month 6, and 70.4 and 49.3 at month 12, respectively. In a multivariate analysis, persistence of seroprotection 12 months after vaccination was negatively associated with current smoking (odds ratio = 0.6, P = 0.03) and positively related with the AS03A-adjuvanted H1N1v vaccine (odds ratio = 2.7, P = 0.0002). CONCLUSION: In HIV-1-infected adults, two doses of adjuvanted influenza vaccine induce long-term persistence of immune response up to 1 year after vaccination.
ISSN: 0269-9370

hal-00875148
https://hal.archives-ouvertes.fr/hal-00875148
DOI : 10.1097/QAD.0b013e328359f27a
PUBMED : 23018437

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
Lionnet et al. recently reported a high prevalence of retinopathy (RET) and otologic disorders (OTD) in patients with sickle cell-hemoglobin C disease (SC), while a significant number of patients had renal diseases (mainly glomerulopathy; GLO) and osteonecrosis (OST). The pathophysiological processes of these complications in SC are not well defined, although blood hyperviscosity has been suspected, but never tested to the best of our knowledge, as responsible for several chronic complications in SC disease1,2. The aim of this study was to analyze the associations between hematological and hemorheological parameters and chronic complications in adult SC patients.
ISSN: 0390-6078

inserm-01081709
http://www.hal.inserm.fr/inserm-01081709
http://www.hal.inserm.fr/inserm-01081709/document
http://www.hal.inserm.fr/inserm-01081709/file/2014%2C%20Lemonne%20-%20Impaired%20blood%20rheology%20plays%20a%20role%20in%20the%20chronic%20disorders%20associated%20with%20sickle%20cell-hemoglobin%20C%20disease.pdf
PUBMED : 24633868

Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVE: To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments. DESIGN: Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months. SETTING: University hospitals. PATIENT(S): Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (+/-) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied. INTERVENTION(S): Semen analyses and aneuploidy study by FISH were performed at each time point. MAIN OUTCOME MEASURE(S): Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment. RESULT(S): Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD +/- radiotherapy or CHOP/MOPP-ABV. After ABVD +/- radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment. CONCLUSION(S): Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.
Fertility and sterility

hal-01477204
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477204
DOI : 10.1016/j.fertnstert.2016.10.001
PUBMED : 27810161

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Lead in homes is a well-known source of childhood lead exposure,which is still of concern due to the health effects of low lead doses. This study aims to describe lead contamination in the homes of children aged 6 months to 6 years in France (without overseas). Between October 2008 and August 2009 ,484 housing units were investigated. Lead in tap water and total and leachable lead levels from floor dust, outdoor soils and paint chips were measured. X-ray fluorescence measurements were carried out on non-metallic and metallic substrates. Nationwide results are provided. The indoor floor dust lead (PbD) geometric mean (GM) was 8.8 microg/m2 (0.8 microg/ft2) and 6.8 mmicrog/m2 (0.6 mg/ft2) for total and leachable lead respectively; 0.21% of homes had an indoor PbD loading above 430.5 microg/m2 (40 microg/ft2). The outdoor play area concentration GM was 33.5microg/kg and 21.7microgkg in total and leachable lead respectively; 1.4% of concentrations were higher than or equal to 400microg/kg. Outdoor floor PbD GM was 44.4 mg/m2 (4.1 mg/ft2) that was approximately 3.2 times higher than the GM of indoor PbD. Lead-based paint (LBP) was present in 25% of dwellings, LBP on only non-metallic substrates was present in 19% of homes and on metallic substrates in 10% of dwellings. The GM of lead concentrations in tap water was below 1 microg/L; 58% of concentrations were lower than 1 microg/L and 2.9% were higher than or equal to 10 mg/L. The age cut-off for homes with lead would be 1974 for paint and 1993 for indoor floor dust. This study provides, for the first time, a look at the state of lead contamination to which children are exposed in French housing. Moreover, it provides policy makers an estimate of the number of French dwellings sheltering children where abatement should be conducted.
Environmental Research

hal-00714516
https://hal.archives-ouvertes.fr/hal-00714516

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA(*) IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1(*) 04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology. © 2012 Movement Disorder Society.
ISSN: 0885-3185

inserm-00721562
http://www.hal.inserm.fr/inserm-00721562
http://www.hal.inserm.fr/inserm-00721562/document
http://www.hal.inserm.fr/inserm-00721562/file/Table1.pdf
http://www.hal.inserm.fr/inserm-00721562/file/Table2.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Lead in homes is a well-known source of childhood lead exposure, which is still of concern due to the health effects of low lead doses. This study aims to describe lead contamination in the homes of children aged 6 months to 6 years in France (without overseas). Between October 2008 and August 2009, 484 housing units were investigated. Lead in tap water and total and leachable lead levels from floor dust, outdoor soils and paint chips were measured. X-ray fluorescence measurements were carried out on non-metallic and metallic substrates. Nationwide results are provided. The indoor floor dust lead (PbD) geometric mean (GM) was 8.8 μg/m² (0.8 μg/ft²) and 6.8 μg/m² (0.6 μg/ft²) for total and leachable lead respectively; 0.21% of homes had an indoor PbD loading above 430.5 μg/m² (40 μg/ft²). The outdoor play area concentration GM was 33.5 mg/kg and 21.7 mg/kg in total and leachable lead respectively; 1.4% of concentrations were higher than or equal to 400 mg/kg. Outdoor floor PbD GM was 44.4 μg/m² (4.1 μg/ft²) that was approximately 3.2 times higher than the GM of indoor PbD. Lead-based paint (LBP) was present in 25% of dwellings, LBP on only non-metallic substrates was present in 19% of homes and on metallic substrates in 10% of dwellings. The GM of lead concentrations in tap water was below 1 μg/L; 58% of concentrations were lower than 1 μg/L and 2.9% were higher than or equal to 10 μg/L. The age cut-off for homes with lead would be 1974 for paint and 1993 for indoor floor dust. This study provides, for the first time, a look at the state of lead contamination to which children are exposed in French housing. Moreover, it provides policy makers an estimate of the number of French dwellings sheltering children where abatement should be conducted.
ISSN: 0013-9351

hal-00732138
https://hal.archives-ouvertes.fr/hal-00732138
DOI : 10.1016/j.envres.2012.04.005
PUBMED : 22551852

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Cytomegalovirus (CMV) infection is common among HIV-infected patients but its repercussion on the course of CD4+ and CD8+ T cells after cART initiation remains elusive. The French Dat'AIDS cohort enrolled 5,688 patients on first-line cART, from which we selected patients who achieved HIV suppression for at least 12 months without modification of cART, and for whom CMV serostatus was available. Five hundred and three patients fulfilled the selection criteria (74% male, median age 43 yrs, 15.5% CDC stage C), of whom 444 (88.3%) were seropositive for CMV (CMV+). Multivariate analyses using mixed-linear models adjusted for the time from HIV suppression, sex, age, transmission risk group, duration of HIV follow-up, the interaction between time from HIV suppression and CMV+ serol-ogy, and the nadir CD4 count revealed a negative correlation between CMV+ and CD4: CD8 ratio (coeff. =-0.16; p = 0.001). This correlation was also observed among patients displaying optimal CD4 recovery (!500 cells/mm3 at M12; coeff. =-0.24; p = 0.002). Hence, CMV+ serostatus antagonizes normalization of the CD4:CD8 ratio, although further analyses of the impact of co-morbidities that associate with CMV serostatus, like HCV infection, are needed to elucidate this antagonism formally. However, this might reflect a premature T cell senescence, thus advocating for a close monitoring of T cells in CMV co-infected patients. In addition, our results raise the question of the benefit of treatment for asymptomatic CMV co-infection in HIV-infected patients.
ISSN: 1932-6203

inserm-01418700
http://www.hal.inserm.fr/inserm-01418700
http://www.hal.inserm.fr/inserm-01418700/document
http://www.hal.inserm.fr/inserm-01418700/file/journal.pone.0165774.PDF
DOI : 10.1371/journal.pone.0165774

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The aim of this study was to evaluate the role of family history of cancer and personal history of other medical conditions in the aetiology of the oral cavity cancer in France. METHODS: We used data from 689 cases of oral cavity squamous cell carcinoma and 3481 controls included in a population-based case--control study, the ICARE study. Odds-ratios (ORs) associated with family history of cancer and personal medical conditions and their 95% confidence intervals (95% CI) were estimated by unconditional logistic regression and were adjusted for age, gender, area of residence, education, body mass index, tobacco smoking and alcohol drinking. RESULTS: Personal history of oral candidiasis was related to a significantly increased risk of oral cavity cancer (OR 5.0, 95% CI 2.1-12.1). History of head and neck cancers among the first-degree relatives was associated with an OR of 1.9 (95% CI 1.2-2.8). The risk increased with the number of first-degree relatives with head and neck cancer. CONCLUSION: A family history of head and neck cancer is a marker of an increased risk of oral cavity cancer and should be taken into account to target prevention efforts and screening. Further studies are needed to clarify the association between oral cavity cancer and personal history of candidiasis.
ISSN: 1471-2407

inserm-00913514
http://www.hal.inserm.fr/inserm-00913514
http://www.hal.inserm.fr/inserm-00913514/document
http://www.hal.inserm.fr/inserm-00913514/file/1471-2407-13-560.pdf
DOI : 10.1186/1471-2407-13-560

Éditeur(s) : HAL CCSD
Résumé : International audience
The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.
Mediators of Inflammation

hal-01544268
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01544268
DOI : 10.1155/2017/1359064
PUBMED : 28607531
PUBMEDCENTRAL : PMC5457781