Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
Rev Med Interne ; 43(6): 342-346, 2022 Jun.
Artigo em Francês | MEDLINE | ID: mdl-35643787

RESUMO

INTRODUCTION: The rate of vaccination in HCWs in France remains low. We aimed to analyze the attitude and beliefs of HCWs toward influenza vaccination in Internal Medicine wards. METHODS: We conducted a cross-sectional survey of HCWs in the departments of Internal Medicine of two tertiary hospitals in France. An anonymous questionnaire designed for this study was used to collect demographic, health beliefs and attitudes, and medical knowledge related to the influenza and influenza vaccine. The survey started shortly prior the 2019 influenza season. RESULTS: The surveys were completed by 158 (29[18-62] years-old ; 75.9% female ; 69.6% non-medical workers) of 187 (84.5%) HCWs. Overall, influenza vaccination coverage rate was 50.6% (n=80/158). Higher vaccination coverage was found in physician and in HCWs who had a better knowledge about the virus transmission. The reason to fulfill vaccination recommendations was to protect the patients, their relatives and themselves for more than 80% of HCWs compliant to vaccination recommendation. More than a third of HCWs (n=59/158; 37.3%) refused to be vaccinated or hesitated. Among them, 12 (12/59, 20.3%) believed that influenza vaccine could cause flu. The main reasons for reluctant HCWs to eventually accept to be vaccinated were a mandatory vaccination program and the demonstration of a better vaccine efficacy to prevent the disease. CONCLUSION: Influenza vaccination coverage among HCWs in Internal Medicine remains low. Education campaigns targeting in priority nurses and nurse assistants is mandatory to improve the compliance of HCWs to vaccination recommendation.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adolescente , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Vacinação , Adulto Jovem
5.
Br J Dermatol ; 182(6): 1415-1422, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31487384

RESUMO

BACKGROUND: The early diagnosis of Sézary syndrome (SS) is challenging. Loss of CD7 and CD26 expression on CD4+ T cells is the currently used criterion in the initial diagnosis and staging of patients with SS. OBJECTIVES: Our aim was to evaluate the respective value of CD26, CD7 and KIR3DL2 expression on CD4+ T cells and total lymphocytes at initial diagnosis of SS. METHODS: This prospective study included 254 patients with clinical features consistent with cutaneous T-cell lymphoma seen at our institution between March 2014 and February 2019. Peripheral blood analysis by flow cytometry was performed for each patient at the time of diagnosis and during follow-up. The diagnosis of SS was based on ISCL/EORTC criteria. RESULTS: The presence of KIR3DL2+ Sézary cells (SCs) ≥ 200 µL-1 correlated with the diagnosis of SS, with sensitivity of 88·6% and specificity of 96·3%. All 154 patients with either inflammatory skin disease or other haematological disease had KIR3DL2+ cells < 200 µL-1 , while eight of them had CD4+ CD26- T cells ≥ 1000 µL-1 . Of five patients with SS and lymphopenia, four had CD4+ CD7- T cells < 1000 µL-1 and three had CD4+ CD26- T cells < 1000 µL-1 . However, all of them had KIR3DL2+ CD4+ T cells ≥ 200 µL-1 . Among patients with available samples during evolution, all B1-staged patients with ≥ 200 µL-1 KIR3DL2+ SCs at diagnosis evolved to B2 stage within 7 months. CONCLUSIONS: KIR3DL2 expression on T cells is highly specific and helps the early diagnosis of SS, especially in those patients with lymphopenia. What's already known about this topic? In the ISCL/EORTC cutaneous T-cell lymphoma (CTCL) categorization of blood involvement (B0-B2), B2 is defined as a T-cell receptor clonal rearrangement in blood, associated with high blood-smear Sézary cell (SC) count. Flow cytometry was developed to circumvent interobserver variability of SC manual counts; however, it mostly relies on detection of cells lacking CD7 and/or CD26 expression. We previously reported the reliability of KIR3DL2 as the first positive SC marker. What does this study add? Based on our analysis of 254 patients, we propose that KIR3DL2 be added to the ISCL/EORTC criteria for initial diagnosis of Sézary syndrome (SS) and B2 staging. This marker improved sensitivity of SS B2-stage CTCL diagnosis with a specificity > 95%, especially for patients with lymphopenia. We found KIR3DL2 helped early diagnosis of SS and was more reliable than CD26 in assessing blood tumour burden during therapy. What is the translational message? SC quantification is the major means of staging at initial diagnosis and monitoring blood tumour burden in a clinical trials setting. We recommend using a threshold value of KIR3DL2+ SCs ≥ 200 µL-1 or KIR3DL2+ SCs/lymphocytes ≥ 10% in the diagnostic criteria of SS and propose a novel algorithm for CTCL B2 blood staging.


Assuntos
Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Micose Fungoide/diagnóstico , Estudos Prospectivos , Receptores KIR3DL2 , Reprodutibilidade dos Testes , Síndrome de Sézary/diagnóstico , Neoplasias Cutâneas/diagnóstico
6.
Br J Dermatol ; 181(6): 1315-1317, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31206589
9.
Curr Res Transl Med ; 64(2): 107-13, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27316394

RESUMO

Autologous hematopoietic stem cell transplantation (AHSCT) is currently investigated as treatment for severe and refractory autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), Crohn's disease (CD) and systemic lupus erythematosus. Randomized clinical trials in MS, SSc and CD have shown the efficacy of AHSCT to promote control of disease activity and progression, when compared to conventional treatment. The use of high dose immunosuppressive conditioning is essential to eliminate the autoimmune repertoire, and the re-infusion of autologous hematopoietic stem cells avoids long-term leucopenia by reconstitution of both immune and hematological systems. Recent studies showed that AHSCT is able to deplete the autoimmune compartment and further promote the formation of a new auto-tolerant immune repertoire, reducing the inflammatory milieu and leading to long-term clinical remission without any complementary post-graft treatment. Deep knowledge about the mechanisms of action related to AHSCT-induced remission is required for the management of possible post-AHSCT relapse and improvement of clinical protocols. This paper will review the mechanisms enrolled in the immune response resetting promoted by AHSCT in patients with autoimmune diseases.


Assuntos
Doenças Autoimunes/terapia , Transplante de Células-Tronco Hematopoéticas , Subpopulações de Linfócitos/imunologia , Tolerância a Antígenos Próprios/imunologia , Doenças Autoimunes/imunologia , Seleção Clonal Mediada por Antígeno , Previsões , Sobrevivência de Enxerto , Humanos , Depleção Linfocítica , Receptores de Antígenos de Linfócitos T/imunologia , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Transplante Autólogo
10.
Bone Marrow Transplant ; 49(8): 1089-92, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24842524

RESUMO

Previous studies on regulatory T-cell (Treg) reconstitution after allogeneic hematopoietic SCT (HSCT) have suggested that, within the GVHD process, imbalance between effector T cells and Tregs may be more important than the absolute numbers of circulating Tregs. No study has analyzed naive vs memory Treg reconstitution in a longitudinal cohort with large numbers of patients. The reconstitution of total and subsets of Treg was prospectively analyzed by flow cytometry in 185 consecutive recipients at 3, 6, 12 and 24 months after allogeneic HSCT. The levels of total, naive and memory Tregs increased, mainly within the memory subset, but remained lower than healthy controls up to 2 years after transplantation. Reduced-intensity conditioning and peripheral blood (PBSC) as the source of stem cells were associated with better 3-month reconstitution. In multivariate analysis, PBSC, recipient age ⩽25 and no anti-thymoglobulin in the conditioning regimen were associated with a better Treg reconstitution. Naive Treg long-term reconstitution was mainly influenced by recipient age. Whereas prior acute GVHD impaired Treg reconstitution, Treg subsets (absolute numbers and frequencies relative to CD4(+) T-cell subsets) at 3, 6 and 12 months after HSCT were not associated with the occurrence of a later episode of chronic GVHD.


Assuntos
Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Memória Imunológica , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Linfócitos T Reguladores/patologia , Fatores de Tempo
11.
Transl Psychiatry ; 2: e201, 2012 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-23212585

RESUMO

Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of severe psychotic disorders.


Assuntos
Transtorno Bipolar/virologia , Variações do Número de Cópias de DNA/genética , Retrovirus Endógenos/genética , Genes env/genética , Esquizofrenia/virologia , Toxoplasmose/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/genética , Estudos de Casos e Controles , Retrovirus Endógenos/metabolismo , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esquizofrenia/sangue , Esquizofrenia/genética
12.
Int Immunopharmacol ; 11(6): 652-60, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21255695

RESUMO

Plant polysaccharides present an interesting potential as immunomodulators, particularly in the induction of antitumoral responses, principally because of their molecular complexity and low in vivo toxicity. Activation of dendritic cells (DCs) could improve antitumoral responses usually diminished in cancer patients, and natural adjuvants provide a possibility of inducing this activation. Herein, we investigated the immunomodulatory activity of a neutral plant polysaccharide Galactomannan on human monocyte-derived DCs (MDDC). MDDCs were stimulated with Galactomannan (GLM) from Caesalpinia spinosa and both phenotypic and functional activities were assessed by flow cytometry and real-time PCR. The phagocytic ability of MDDCs was determined by using E-coli pHrodo particles and induction of T-lymphocyte allostimulation was determined after T-cell staining with carboxyfluorescein succinimidyl ester (CFSE). In MDDCs, purified Galactomannan induced phenotypic maturation revealed by increased expression of CD83, CD86, CD206, and HLA-DR. Functional experiments showed the loss of particulate antigen uptake in Galactomannan-stimulated DCs and increased alloantigen presentation capacity. Finally, Galactomannan increased protein and mRNA levels of pro-inflammatory cytokines including IL-1ß, IL-6, IL-8, IL-12p70, and TNF-α. These data reveal that Galactomannan obtained from Caesalpinia spinosa promotes effective activation of MDDCs. This adjuvant-like activity may have therapeutic applications in clinical settings where immune responses need boosting.


Assuntos
Adjuvantes Imunológicos/farmacologia , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Mananas/farmacologia , Apresentação de Antígeno/efeitos dos fármacos , Antígenos de Diferenciação/metabolismo , Caesalpinia/imunologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Separação Celular , Citocinas/genética , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Citometria de Fluxo , Galactose/análogos & derivados , Humanos , Ativação Linfocitária/efeitos dos fármacos , Teste de Cultura Mista de Linfócitos , Fagocitose/efeitos dos fármacos , Linfócitos T/imunologia
13.
14.
Lancet ; 354(9190): 1598-603, 1999 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-10560675

RESUMO

BACKGROUND: Granulomatous syndromes, such as Wegener's granulomatosis, are defined according to complex criteria, but the underlying cause is rarely identified. We present evidence for a new aetiology for chronic granulomatous lesions associated with a recessive genetic defect, which is linked to the human leucocyte antigen (HLA) locus. METHODS: Five adults with necrotising granulomatous lesions in the upper respiratory tract and skin, associated with recurrent bacterial respiratory infections and skin vasculitis, were identified. A diagnosis of Wegener's granulomatosis was considered in all of them, but abandoned because of an incompatible disease course and resistance to immunosuppressive treatments. Peripheral-blood samples were taken and analysed by immunohistochemistry and fluorescent-activated-cell-sorter analysis. Since all five patients were homozygous for the HLA locus, we looked for genetic defects located within the HLA-locus with PCR and restriction fragment length polymorphism. FINDINGS: A severe decrease in cell-surface expression of HLA class-I molecule was seen in all patients. Defective expression of the transporter associated with antigen presentation (TAP) genes was responsible for the HLA class-I down-regulation, and in two patients we identified a mutation in the TAP2 gene responsible for the defective expression of the TAP complex. We showed the presence of autoreactive natural killer (NK) cells and gammadelta T lymphocytes in the peripheral blood cells of two patients. Correction of the genetic defect in vitro restored normal expression of HLA class-I molecules and prevented self-reactivity in the patients' cells. Histology of granulomatous lesions showed the presence of a large proportion of activated NK cells. INTERPRETATION: Our findings define the cause and pathogenesis of a new syndrome that affects patients with a defective surface expression of HLA class-I molecules. The syndrome resembles Wegener's granulomatosis both clinically and histologically. Patients have chronic necrotising granulomatous lesions in the upper respiratory tract and skin, recurrent infections of the respiratory tract, and skin vasculitis. A predominant NK population within the granulomatous lesions suggests that the pathophysiology of the skin lesions may relate to the inability of HLA class-I molecules to turn off NK cell responses. Accurate genetic analysis of a defined syndrome can provide a better understanding of the cause and pathogenesis of a disease.


Assuntos
Doença Granulomatosa Crônica/genética , Antígenos de Histocompatibilidade Classe I/genética , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/imunologia , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Alelos , Western Blotting , Códon , Diagnóstico Diferencial , Regulação para Baixo , Feminino , Granulomatose com Poliangiite/diagnóstico , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imuno-Histoquímica , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Mutação , Fenótipo , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
J Immunol ; 163(11): 6045-52, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10570292

RESUMO

Generation of the HLA-A0201 (A2) influenza Matrix 58-66 epitope contained within the full-length Matrix protein is impaired in cells lacking the proteasome subunits low molecular protein 2 (LMP2) and LMP7. This Ag presentation block can be relieved by transfecting the wild-type LMP7 cDNA into LMP7-deficient cells. A mutated form of LMP7, lacking the two threonines at the catalytic active site, was equally capable of relieving the block in presentation of the influenza Matrix A2 epitope. These observations were extended by analyzing whether modification of the influenza Matrix protein could overcome the block in presentation of the A2 Matrix epitope. Expression of either a rapidly degraded form of the full-length Matrix protein or shorter Matrix fragments led to an efficient presentation of the A2 influenza Matrix epitope by LMP7-negative cells. These findings demonstrate two main points: 1) LMP7 incorporation into the proteasome is of greater importance for the generation of the influenza A2 Matrix epitope than the presence of the LMP7's catalytic site; and 2) the interplay between cytosolic proteases and stability of target proteins is of importance in optimization of Ag presentation. These observations may have relevance to the immunodominance of tumor and viral epitopes and raise the possibility that generation of shorter protein fragments could be a mechanism to ensure optimal Ag presentation by cells expressing low levels of LMP7.


Assuntos
Apresentação de Antígeno , Cisteína Endopeptidases/metabolismo , Epitopos Imunodominantes , Vírus da Influenza A/imunologia , Complexos Multienzimáticos/metabolismo , Fragmentos de Peptídeos/imunologia , Proteínas da Matriz Viral/imunologia , Meia-Vida , Fragmentos de Peptídeos/metabolismo , Complexo de Endopeptidases do Proteassoma , Processamento de Proteína Pós-Traducional , Proteínas/genética , Proteínas/metabolismo , Proteínas da Matriz Viral/metabolismo
16.
Hum Immunol ; 42(3): 195-202, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7759306

RESUMO

MS is an autoimmune demyelinating disease that has been known to be associated with the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype. TAP1 and TAP2, two genes encoded within the MHC class II region between HLA-DP and -DQ loci, display genetic variability and are involved in the transport of antigenic peptides from the cytoplasm to the endoplasmic reticulum. Comparison of 116 MS patients with Caucasoid controls did not reveal any significant correlation between the previously described alleles of the TAP1 and TAP2 genes and MS. We report here an additional TAP2 dimorphism at codon 386, called I and J, corresponding to a silent mutation. An increased frequency of the J variant was observed in the patient population. The J mutation was not found in linkage disequilibrium with the HLA-DRB1*1501 allele and can be considered an additional genetic susceptibility marker of the disease.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Esclerose Múltipla/genética , Polimorfismo Genético/genética , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Sequência de Aminoácidos , Sequência de Bases , Predisposição Genética para Doença , Antígenos HLA-D/genética , Humanos , Dados de Sequência Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA