Mûr-de-Bretagne, France
Mûr-de-Bretagne, France

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Corpechot C.,University Pierre and Marie Curie | Chretien Y.,University Pierre and Marie Curie | Johanet C.,Service dImmunologie | Chazouillres O.,University Pierre and Marie Curie | Poupon R.,University Pierre and Marie Curie
Journal of Hepatology | Year: 2012

Background & Aims: Smoking has been identified as a potential predisposition factor for primary biliary cirrhosis (PBC). However, it remains unclear whether it is associated with more active and severe disease. Our aim was to assess the relationships between smoking and the severity of the elementary histological lesions, as well as the biochemical and immunological features of PBC. Methods: Smoking history data were collected from 223 PBC patients using a standardized questionnaire. Histological data were available in 164 patients at presentation. Liver fibrosis and histological inflammatory activity were semi-quantified according to a METAVIR-based classification system. Odds ratios (OR) were assessed using a logistic regression analysis. Results: Smoking history prior to diagnosis was reported in 58 patients (26%). Twenty-five patients (11%) were active smokers at diagnosis. Male gender (OR, 4.5), alcohol intake >20 g/d (OR, 4.2), and F3-F4 fibrosis stage (OR, 2.7), but not inflammatory grade, bile duct changes, biochemical or immunological features, were associated with smoking history. Smoking intensity was significantly higher in patients with F3-F4 stage (8.1 ± 14.2 pack-years vs. 3.0 ± 7.0 pack-years; p = 0.01). Adjusted logistic regression identified smoking history and smoking intensity as independent risk factors of advanced fibrosis. Each pack-year of increase in smoking intensity was associated with a 5.0% (95% CI, 1.3-8.7%) increased likelihood of advanced fibrosis. Conclusions: Smoking increases, in a dose-dependent fashion, the risk of liver fibrosis in PBC without apparent increase in the histological inflammatory activity, bile duct lesions, biochemical, and immunological features of the disease. PBC patients should be strongly encouraged not to smoke. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


PubMed | Laboratoire dImmunologie and Service dImmunologie
Type: Journal Article | Journal: Immunologic research | Year: 2016

Autoantibodies are a common feature of rheumatoid arthritis (RA), and their detection is used as a diagnostic tool in medical practice. Rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) detection in patients sera are now included in 2010 ACR/EULAR criteria for RA diagnosis. In this study, we evaluated a new vimentin-derived ACPA ELISA, the anti-cyclic citrullinated peptide high sensitive (CCP hs) test, and we compared its performance with the RF IgM and anti-CCP3 tests on a French multicenter cohort of 84 RA patients, 107 non-RA patients and 100 healthy controls. Sensitivities for RA diagnosis were 71.4, 84.5 and 64.3 % and specificities were 88.4, 86.9 and 87.3 % for CCP hs, CCP3 and RF IgM, respectively. There was a moderate correlation between CCP hs and CCP3 titers (Pearsons r = 0.43; p < 0.0001). These results support the contention that anti-CCP hs antibodies are new reliable ACPA with high specificity for RA.


PubMed | French National Center for Scientific Research, Service dImmunologie, Clermont University and French National Institute for Agricultural Research
Type: | Journal: Journal of immunology research | Year: 2016

Bacterial vaginosis (BV), the most common genital infection in reproductive-aged women, is associated with increased risk of sexually transmitted infections. Its etiology remains unclear, especially the role of Gardnerella (G.) vaginalis, an anaerobic bacterium characteristic of the BV-alteration of the vaginal ecosystem. In the genital mucosa, dendritic cells (DCs) sense bacteria of the microenvironment via receptors and then orchestrate the immune response by induction of different T cell subtypes. We investigated the interactions between G. vaginalis and human monocyte-derived DCs using a wide range of bacterial concentrations (multiplicity of infection from 0.01 to 100), and the effects of this pathogen on PHA-induced lymphocyte proliferation. As observed by electron microscopy and cytometry, G. vaginalis reduced the internalization ability of DCs by forming extracellular clusters and induced neither DC maturation, nor DC secretion of cytokines, except at the highest dose with a very early DC maturation state. The same profile was observed on lymphocytes with significant increases of proliferation and cytokine secretion only at the highest bacterial concentration. Our findings indicate that G. vaginalis possesses slight immune-stimulating activities against DCs and T cells, reflecting thus a defective inflammatory response and giving rise to the atypical, non- or low-grade, inflammatory clinical disease profile.


PubMed | Pediatrie Generale, Groupe Hospitalier Est, Lyon University Hospital Center, University of Lyon and 16 more.
Type: | Journal: Joint, bone, spine : revue du rhumatisme | Year: 2016

Studies of early-onset systemic lupus erythematosus (SLE) have identified monogenic forms of the disease. The primary objective of this study was to compare the clinical and laboratory features of the first patients included in the GENIAL/LUMUGENE cohort to those reported in previous publications. The secondary objective was to determine whether subgroups with a distinctive pattern of clinical and biological features are seen in predominantly genetic forms of SLE.GENIAL/LUMUGENE is a French nationwide study of the clinical, immunological, and genetic features of juvenile-onset SLE (clinicaltrials.gov #NCT01992666). Clinical and laboratory data from the first 64 patients younger than 18 years who were included in the first part of the study were collected retrospectively. Predefined criteria were used to divide the patients into three subgroups: syndromic SLE (n=10) and familial SLE (n=12) - both presumed to have a strong genetic component -- and other forms of early-onset SLE (n=42).The predefined criteria for identifying subgroups based on knowledge of the clinical and epidemiological features of monogenic SLE showed a significantly younger age at onset in syndromic SLE (P<0.05) and a lower frequency of joint manifestations in familial SLE.In this study, clinical and epidemiological data alone failed to identify a specific patient subgroup characterized by the same disease presentation or progression. This result may be related to the small sample size or indicate marked heterogeneity of juvenile-onset SLE. Genetic studies using new sequencing techniques in these patients might identify genetic factors responsible for marked phenotypic variability.


Tattevin P.,Service des Maladies Infectieuses et Reanimation Medicale | Tattevin P.,French Institute of Health and Medical Research | Monnier D.,Service dImmunologie | Monnier D.,French Institute of Health and Medical Research | And 10 more authors.
Journal of Infectious Diseases | Year: 2010

Background. Severe sepsis results in a sustained deleterious immune dysregulation. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism, plays a pivotal role in immune tolerance and is induced during various inflammatory conditions. Methods. Plasma samples obtained from patients with septic shock (n = 38), severe sepsis (n = 35), or sepsis (n = 10) and from healthy donors (n = 26) were analyzed for IDO activity by high-performance liquid chromatography. Lymphocyte, monocyte, and regulatory T cell counts as well as monocytic human leukocyte antigen DR (HLA-DR) expression were quantified by flow cytometry. Peripheral blood mononuclear cells and purified CD14+ and CD14- fractions were assayed in vitro for spontaneous and inducible IDO expression and activity. Results. IDO activity gradually increased according to sepsis severity, and septic patients who died had higher IDO activity on admission than did survivors (P =0.013). Monocytes were a major source of active IDO in normal peripheral blood. The percentage and absolute number of circulating CD14+ cells were increased in septic patients, and their monocytes remained fully able to produce functional IDO after NF-κB-independent interferon γ stimulation but not through NF-κB-dependent Toll-like receptor engagement. Conclusions. IDO activity is increased during severe sepsis and septic shock and is associated with mortality. IDO production could be used to better characterize monocyte reprogramming in sepsis. © 2010 by the Infectious Diseases Society of America. All rights reserved.


PubMed | Service de pneumologie, Service dimmunologie, Service de radiologie, University of Rennes 1 and Service de reanimation medicale
Type: | Journal: Revue des maladies respiratoires | Year: 2016

Auto-immune pulmonary alveolar proteinosis is a rare disorder characterized by the accumulation of surfactant proteins in the alveoli.We report a case of a 41-year-old smoker, presenting initially with acute respiratory failure. Whole lung lavages were effective initially but only for a few weeks. GM-CSF subcutaneous injections were not effective, and then plasmapheresis were tried.This is the fifth report of the use of this treatment in auto-immune pulmonary alveolar proteinosis. Plasmapheresis was not effective in our patient.


Moulignier A.,Rothschild | Mikol J.,Service dAnatomie et Cytologie Pathologiques | Heran F.,Rothschild | Galicier L.,Service dImmunologie
BMJ Case Reports | Year: 2014

Primary histiocytic sarcoma (HS) of the central nervous system (CNS) is a rare haematopoietic neoplasm. The inconsistent terminology and diagnostic criteria currently used for CNS HS have complicated the appreciation of the clinical aspects of the disease. The main differential diagnoses are non-Hodgkin's lymphoma, reactive histiocytic proliferation, dendritic cell neoplasm, undifferentiated carcinoma, inflammatory pseudotumour, Rosai-Dorfman disease and abscess. The true diagnosis of CNS HS requires an extensive immunophenotypic workup using specific histiocytic markers, such as CD163, with the exclusion of markers of other cell lineages. This clinicopathological case report describes an improved approach towards the differential diagnosis of CNS HS. Copyright 2014 BMJ Publishing Group. All rights reserved.


Sallee M.,Aix - Marseille University | Daniel L.,Service dAnatomo pathologie | Piercecchi M.-D.,Service de Medecine Legale et Droit de la Medecine | Jaubert D.,Aix - Marseille University | And 3 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Cardiac complications are frequently seen in thrombotic thrombocytopaenic purpura related to ADAMTS13 deficiency. We describe the case of a 43-year-old woman who was diagnosed with an atypical haemolytic-uraemic syndrome (aHUS) associated with a pathogenic mutation in the factor H gene (C623S). After 15 days of treatment, she suffered a sudden cardiac arrest and died despite intensive resuscitation attempts. She showed only one cardiovascular risk factor, hypercholesterolaemia. Her sudden death was secondary to cardiac infarction related to a coronary thrombotic microangiopathy. This is the first case of aHUS related to a mutation in the factor H gene associated with cardiac microangiopathy. This case emphasizes the need to screen for cardiac complication during the treatment of aHUS. © 2010 The Author.


Grealy R.,St James's Hospital | White M.,St James's Hospital | Stordeur P.,Service dImmunologie | Kelleher D.,St James's Hospital | And 3 more authors.
Mediators of Inflammation | Year: 2013

Introduction. Severe sepsis in humans may be related to an underlying profound immune suppressive state. We investigated the link between gene expression of immune regulatory cytokines and the range of illness severity in patients with infection and severe sepsis. Methods. A prospective observational study included 54 ICU patients with severe sepsis, 53 patients with infection without organ failure, and 20 healthy controls. Gene expression in peripheral blood mononuclear cells (PBMC) was measured using real-time polymerase chain reaction. Results. Infection differed from health by decreased expression of the IL2, and IL23 and greater expression of IL10 and IL27. Severe sepsis differed from infection by having decreased IL7, IL23, IFNγ, and TNFα gene expression. An algorithm utilising mRNA copy number for TNFα, IFNγ, IL7, IL10, and IL23 accurately distinguished sepsis from severe sepsis with a receiver operator characteristic value of 0.88. Gene expression was similar with gram-positive and gram-negative infection and was similar following medical and surgical severe sepsis. Severity of organ failure was associated with serum IL6 protein levels but not with any index of cytokine gene expression in PBMCs. Conclusions. Immune regulatory cytokine gene expression in PBMC provides a robust method of modelling patients' response to infection. © 2013 Robert Grealy et al.


PubMed | Service de nephrologie CHU dOran, Service de reanimation pediatrique CHU dOran, Service dimmunologie and Service de cardiologie
Type: Journal Article | Journal: Annales de cardiologie et d'angeiologie | Year: 2016

Malignant hypertension (HTA), pediatrics, is unique by its clinical presentation, defined as severe hypertension accompanied by ischemic failure of one or more organs.Retroprospective study of cases of children admitted to pediatric intensive care. We chose a decline of 10 years from September 1994 to December 2004 for the first time, and from January 2005 to December 2015 for the second period; and we identified the cases presenting malignant hypertension (mHTA).Sixty-six patients were included, a prevalence of 0.6%. The age of patients ranged from 12months to 16years. The symptoms are related to the consequences of hypertension or condition in question. The most found signs are headache in more than 7%. Cerebrovascular event in 6%. A hypertensive convulsive encephalopathy 33.3% of patients. Renal disease is common, of varying severity. A fundus retinopathy was found in 47% stage 3, stage 4 in 51%. mHTA defined for the mean SBP values of 175mmHg and DBP average 112,5mmHg is often secondary to renal causes. The treatment is symptomatic with antihypertensive associated with the etiological treatment. Evolution is good out of 7 deaths.mHTA is a rare condition in the pediatric population. The clinical signs of functional rich under their impact on vital organs. The support must be early in intensive care.

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