RESUMO
The immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disease characterized by targeted chromosome breakage, directly related to a genomic methylation defect. It manifests with phenotypic and clinical variability, with the most consistent features being developmental delay, facial anomalies, cytogenetic defects and immunodeficiency with a reduction in serum immunoglobulin levels. From the molecular point of view, ICF syndrome was always divided into ICF type I (ICF1) and ICF type 2 (ICF2). Mutations in DNMT3B gene are responsible for ICF1, while mutations in ZBTB24 have been reported to be responsible for ICF2. In this study, we describe a Lebanese family with three ICF2 affected brothers. Sanger sequencing of the coding sequence of ZBTB24 gene was conducted and revealed a novel deletion: c.396_397delTA (p.His132Glnfs*19), resulting in a loss-of-function of the corresponding protein. ZBTB24 belongs to a large family of transcriptional factors and may be involved in DNA methylation of juxtacentromeric DNA. Detailed molecular and functional studies of the ZBTB24 and DNMT3B genes are needed to understand the pathophysiology of ICF syndrome.
Assuntos
Síndromes de Imunodeficiência/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Sequência de Aminoácidos , Criança , Pré-Escolar , Aberrações Cromossômicas , Cromossomos Humanos/genética , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , Análise Mutacional de DNA , Face/anormalidades , Face/patologia , Feminino , Deleção de Genes , Testes Genéticos/métodos , Humanos , Síndromes de Imunodeficiência/patologia , Líbano , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , Doenças da Imunodeficiência Primária , DNA Metiltransferase 3BRESUMO
A serosurvey for Human T-cell Lymphotropic virus type 1 (HTLV-I)/HTLV-II was conducted in 1,900 blood donors, 120 pregnant women and 436 high-risk group patients in Beirut, Lebanon. One of the 1,900 blood donors was anti-HTLV-I/II-seroreactive on screening by enzyme immunoassay (EIA) but was indeterminate by Western blot and negative by polymerase chain reaction. None of the other 556 subjects studied was seroreactive by EIA. The credibility of the zero prevalence of HTLV-I/II infection among the Lebanese blood donors is supported by the absence of seroreactivity of antibodies in the multiply transfused patients. It seems therefore that the prevalence of HTLV-I/II appears to be less than 1 in 2,456 in the Lebanese population and hence, HTLV-I/II infection does not appear to require routine screening in Lebanon.
Assuntos
Doadores de Sangue , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Adolescente , Adulto , Doadores de Sangue/estatística & dados numéricos , Anticorpos Antideltaretrovirus/imunologia , Anticorpos Antideltaretrovirus/isolamento & purificação , Feminino , Infecções por HTLV-I/sangue , Infecções por HTLV-I/virologia , Infecções por HTLV-II/sangue , Infecções por HTLV-II/virologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Humanos , Líbano/epidemiologia , Masculino , Programas de Rastreamento , Gravidez , Prevalência , Fatores de RiscoRESUMO
The importance of sexual transmission in the epidemiology of hepatitis G virus (HGV) and hepatitis C virus (HCV) was evaluated in two groups of HIV-1-positive Lebanese patients. Members of one group (90 patients) were HIV-1-infected via sexual route and denied intravenous drug (IVD) use, while members of the other group (28 patients) became HIV-1-infected parenterally and confessed frequent IVD use. The overall prevalence of HGV infection was relatively high in both groups and with no statistically significant difference between them (28% among IVD users vs 32% among the non-IVD users) despite the fact that non-IVD users were significantly older (32.7 +/- 1.7 years) than the IVD users (24.0 +/- 1.4 years) (P < 0.01). Conversely, there was a clear association between IVD use and HCV infection (25% for IVD users vs 7% for non-IVD users) despite the significantly lower age of the IVD users. These results point to the efficient transmission of HGV via the sexual route, while the transmission of HCV is mainly via the parenteral route. CD4+ lymphocyte counts were known on only 82 HIV1-infected patients. Although the number of HGV-RNA-positive patients (three) was small compared with anti-HGV-positive patients (24), a relationship was not found between CD4+ lymphocyte counts and the presence of HGV-RNA in the HIV-1-positive patients. The role of HGV in causing significant liver disease is still under dispute.
Assuntos
Infecções por Flaviviridae/transmissão , Vírus GB C , Hepatite Viral Humana/transmissão , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Distribuição por Idade , Contagem de Linfócito CD4 , Feminino , Infecções por Flaviviridae/epidemiologia , Infecções por HIV/epidemiologia , HIV-1 , Hepatite Viral Humana/epidemiologia , Humanos , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/análiseRESUMO
The HLA-A, -B, -DR and DQ phenotypes have been defined in a panel of 217 Lebanese. These subjects were all unrelated, belonged to different religious communities and originated from the various provinces of Lebanon. All the broad class I specificities tested, except splits A25(10), B54(22) and B56(22), were present in this panel. When HLA-A and -B antigen frequencies were compared with data on the Caucasoids, Negroids and Orientals, several similarities in antigen frequencies could be found between some frequencies observed in the Lebanese and those observed in the Negroids and/or Orientals. There were no frequencies equivalent to those particular to the Caucasoids. In addition, two groups of class I antigens could be distinguished: a first group (A32, B14, B18, B35, B38, B39, B41 and B50) showing higher frequencies, and a second group (A31, B27, B60 and B62) showing lower frequencies than those observed in the Caucasoids, Negroids and Orientals. However, when analysed separately, several mediterranean ethnic groups, notably the Greeks and Italians, have a frequency profile equivalent to that of the Lebanese, with the exception of the B41 specificity, which is particularly high in the Lebanese (14.2%). The data concerning the class II antigens are the most interesting. All the specificities were present in the panel. The HLA-DR5 is the highest frequency of DR antigens in the present panel (58.9%) and nearly all DR5 positive individuals are DR11. The DR11 allele accounts for 33.1% of the total DR gene frequency. The highest DQ antigen frequency is that of DQ3 (76.4%), the majority of which is DQ7 (66.4%). We observed a high DR11-DQ7 haplotype frequency (29.4%) with a significant delta value for linkage disequilibrium. There is no linkage disequilibrium between B41 and DR11. The commonly observed linkage disequilibrium between the DQ5 allele, and the DR1, DR2, DR10 and DR14 alleles are not significant in this Lebanese panel.
Assuntos
Antígenos HLA/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Epitopos , Feminino , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Humanos , Líbano , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
The agent of the majority of parenterally transmitted non-A, non-B hepatitis is the hepatitis C virus (HCV). In this study, we estimate the HCV seropositivity in 7,771 blood donors and 317 patients on hemodialysis in 5 different centres, of which 4 are situated in Beirut. The used screening test consists of a second generation EIA technique. The study shows that 0.41% of blood donors are HCV seropositive. The mean percentage of seropositive patients is about 27% but the comparison of centres among them showed a high variability (10, 19, 21, 33 et 39%). The blood transfusion, the number of years on hemodialysis and the screening of blood donors seem to be the main risk factors. Reducing the number of transfusions to hemodialysed patients and screening antibodies anti-HCV in blood donations are primordial.
Assuntos
Doadores de Sangue , Hepacivirus/isolamento & purificação , Diálise Renal , Adolescente , Adulto , Idoso , Doadores de Sangue/estatística & dados numéricos , Feminino , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Anticorpos Anti-Hepatite C/sangue , Humanos , Técnicas Imunoenzimáticas , Líbano/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Diálise Renal/estatística & dados numéricos , Fatores de Risco , Estudos Soroepidemiológicos , Fatores de Tempo , Reação TransfusionalAssuntos
Anticorpos/sangue , Proteínas do Sistema Complemento/imunologia , Citotoxicidade Imunológica , Antígenos HLA/imunologia , Transplante de Rim/imunologia , Especificidade de Anticorpos , Linfócitos B/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo/métodos , Antígenos HLA-D/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Linfócitos T/imunologia , Listas de EsperaRESUMO
Recently we identified hepatitis C virus (HCV) genotype 4 as the principle genotype among Lebanese thalassaemics. In an attempt to confirm the predominance of genotype 4 in Lebanon and perhaps in the Middle East, genotyping was attempted on 142 HCV-infected Lebanese patients from five different hospitals in the country. These included 38 HCV-positive patients with symptomatic liver disease who were referred to gastroenterologists and 104 HCV-positive patients with no symptoms of liver disease: 27 patients with thalassaemia, 30 patients on haemodialysis, 32 multi-transfused and 15 intravenous drug users. HCV genotyping was performed on PCR HCV RNA-positive samples using a commercial line probe assay (LiPA; Innogenetics, Ghent, Belgium). HCV genotype 4 is found to be the predominant genotype among HCV-infected Lebanese patients (ranging from 34.2% to 53.3%) followed by 1a (ranging from 12.5% to 43.3%) and 1b (ranging from 8.0% to 34.4%). In patients with symptomatic liver disease, however, genotype 4 (34.2%) was preceded by genotype 1a (39.5%). The predominance of HCV genotype 4 in our population (45.7%) confirms the predominance of HCV genotype 4 in Lebanon and most of the Arab countries in the Middle East but contrasts with data reported from non-Arab Middle Eastern Countries as can be seen from the literature review. Implications of genotyping for clinical outcome of HCV infection, response to treatment as well as for vaccine development are discussed.
Assuntos
Hepacivirus/classificação , Hepatite C/virologia , Adulto , Feminino , Genótipo , Hepacivirus/genética , Humanos , Líbano , Masculino , Pessoa de Meia-Idade , Oriente MédioRESUMO
During a 2-year period, blood samples from 2505 Lebanese blood donors were chosen at random, at various periods of time at one blood donation centre (Hotel Dieu de France, Beirut, Lebanon) and were screened for markers of HBV infection (HBsAg, anti-HBc and anti-HBs). The study showed HBsAg positivity of 0.6% and an overall exposure rate to HBV of 10.0%. Out of the 2505 blood donors screened, 56 (22%) were found to be 'anti-HBc alone' positive which is almost four times the HBsAg positivity. The 56 'anti-HBc alone' samples were retested by another ELISA kit commercially available and 54 samples were 'anti-HBc alone' positive by both assays. The 54 samples had no serological markers as evidence of infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Only seven (13%) out of the 54 samples were HBV DNA positive by PCR and all were HBV genotype D. All seven HBV DNA-positive samples had HBV DNA levels below 400 copies/ml. Although any circulating HBV DNA among our 'anti-HBc alone' blood donors was below the detection limit of our Amplicor Monitor assay, some of these samples had circulating virus. A national study, where a larger number of blood donors from different blood donation centres across the country will perhaps determine whether screening for anti-HBc in addition to HBsAg detection is needed in Lebanese blood donors.
Assuntos
Doadores de Sangue , Anticorpos Anti-Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B/diagnóstico , Adulto , Biomarcadores/sangue , Sangue/virologia , DNA Viral/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B/epidemiologia , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/análise , Humanos , Incidência , Líbano/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Medição de Risco , Estudos de Amostragem , Sensibilidade e Especificidade , Carga ViralRESUMO
Three groups of Lebanese patients (haemophiliacs, patients on cycled cancer chemotherapy who were regularly receiving blood transfusions, and intravenous drug users) and a control group of healthy blood donors were checked for markers of infection with hepatitis viruses (B and C) and human retroviruses (HIV and HTLV-I). Compared with the controls, all three groups of patients were more likely to be seropositive for antibody to hepatitis C virus (anti-HCV), and the haemophiliacs and cancer patients (but not the relatively young drug users) were more likely to be seropositive for hepatitis B virus (HBV). All the haemophiliacs and cancer patients found to be carrying the surface antigen of HBV (HBsAg) and/or to be seropositive for anti-HCV had given the same result when tested before the screening of blood and blood products for HBsAg and anti-HCV became routine practice in Lebanon (a decade before the present study). The four intravenous drug users (IVDU) found seropositive for HBV (two cases) or anti-HCV (two cases) had seroconverted in the 2 years prior to the present study. In addition to highlighting the problem of HCV infection among IVDU, the present results emphasise the need for the careful screening of donated blood for all blood-borne viruses, and for the exclusive use of disposable equipment in the management of cancer patients. The anti-HBV vaccination of IVDU is recommended but only the results of further clinical evaluation will show whether the similar vaccination of patients on cycled cancer chemotherapy is of value. Although none of the patients or controls was found positive for anti-HIV-1, anti-HIV-2 or anti-HTLV-I, the routine screening of blood and blood products for these viruses (particularly for HIV) should remain mandatory.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HTLV-I/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Adulto , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Transfusão de Sangue , Feminino , Genótipo , Infecções por HIV/imunologia , Infecções por HTLV-I/imunologia , Hemofilia A/complicações , Hemofilia A/epidemiologia , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/imunologia , Humanos , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , RNA Viral/sangue , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Exposure to hepatitis C virus (HCV), hepatitis G virus (HGV) and the carrier 'rate' for hepatitis B virus (HBsAg) were investigated in thalassaemia patients in Lebanon, a group that has not been studied in the past. The HCV genotypes and their distribution in the 395 thalassaemics, all of whom had been registered at the Chronic Care Center (CCC) in Hazmieh since 1996, were also studied. Of the 55 samples (14%) found positive for anti-HCV, 19 were also positive for HCV RNA. The 19 samples of HCV RNA were mostly of genotype 4 (37%), followed by 1a and 3a (21% each), lb (16%) and 2b (5%). Most (14; 74%) of the 19 HCV-RNA-positive samples, but only 13 (36%) of the 36 samples that were negative for HCV RNA although anti-HCV-positive, were positive for anti-HGV. Among 100 anti-HCV-negative samples, eight (8%) were anti-HGV positive. Only one (0.28%) of all 395 patients investigated was found to be HBsAg-positive. All of the HBV- and HCV-positive patients had initially been found positive in 1996, when they were first registered at the CCC, and none of the remaining patients had seroconverted since. As none of the patients had been checked for anti-HGV until the present study, the history of their exposure to HGV was unknown. These results emphasise the importance of screening all blood donations collected in Lebanon for HBsAg and anti-HCV. This and stringent infection-control measures are necessary steps to limit the spread of HBV, HCV and perhaps HGV to thalassaemics.
Assuntos
Hepacivirus/genética , Hepatite Viral Humana/epidemiologia , Talassemia beta/complicações , Adolescente , Adulto , Criança , Feminino , Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/epidemiologia , Vírus GB C , Genótipo , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Hepatite Viral Humana/complicações , Humanos , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Soroepidemiológicos , Reação Transfusional , Talassemia beta/terapiaRESUMO
Human HLA class I deficiency is a rare disease which, in most of the patients described to date, results from a defect in subunit 1 or 2 of the peptide transporter associated with antigen processing (TAP). The clinical features of TAP deficiency include a chronic inflammation of the respiratory tract and/or granulomatous skin lesions. In this report, we describe two adult siblings with an HLA class I deficiency. One individual had only spontaneously-healing skin granulomatous lesions, while the second did not display any of the symptoms associated with HLA class I deficiency and could be considered to be healthy. We show that the patients display a homozygous TAP2 mutation which blocks the maturation of HLA class I molecules. Cell surface expression of these molecules is strongly reduced, but three times higher than on cells from other previously described TAP-deficient individuals. This higher expression results, at least in part, from the presence of HLA-B7 molecules which are probably empty of peptide. The numbers of CD8+ alphabeta T cells are almost normal in these patients. The anti-EBV T-cell response of one patient is mediated by HLA-B7 restricted CD8+ alphabeta T lymphocytes recognizing the BMRF1 nuclear EBV antigen, demonstrating that CD8+ alphabeta T cells can participate in anti-viral responses. This study shows that TAP deficiency can remain totally asymptomatic for several decades, and suggests that in some cases, TAP-independent immune responses provide efficient protection from most of the common intracellular pathogens.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Deleção de Genes , Antígenos de Histocompatibilidade Classe I/sangue , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Transformada , Feminino , Genótipo , Antígeno HLA-B7/imunologia , Células HeLa , Herpesvirus Humano 4/imunologia , Antígenos de Histocompatibilidade Classe I/classificação , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Mutagênese , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Células Tumorais CultivadasRESUMO
Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by the WHO Nomenclature Committee for Factors of the HLA System. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese patient suffering from ankylosing spondylitis (AS). This new variant differs from the common HLA-B*2705 DNA sequence at five different nucleotide positions. These nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97. Since this novel allele is encountered in an AS patient, the associated sequence changes are not expected to affect significantly neither the presentation of a putative arthritogenic peptide nor the conformation-dependent recognition by effector cells.