RESUMO
BACKGROUND: Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT). RESULTS: This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients' follow-up: the early period (0-30 days after Allo-HSCT), the intermediate period (30-100 days after Allo-HSCT) and the late period (> 100 days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of < 1000 ng/ml (median 6d vs 8d, p = 0.036). MBL levels < 1000 ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00-6.13), neutropenic period (0-30 days, RR 3.28, 95% CI 1.53-7.06) and intermediate period (30-100 days, RR 2.37, 95% CI 1.15-4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels < 1000 ng/ml (hazard ratio 5.55, 95% CI 1.17-26.30, p = 0.03) but not with MBL2 genotype. CONCLUSIONS: Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6 months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.
Assuntos
Suscetibilidade a Doenças , Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Lectina de Ligação a Manose/genética , Viroses/etiologia , Viroses/mortalidade , Adolescente , Adulto , Biomarcadores , Feminino , Predisposição Genética para Doença , Genótipo , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Polimorfismo Genético , Período Pré-Operatório , Prognóstico , Transplante Homólogo , Viroses/diagnóstico , Adulto JovemAssuntos
Anticorpos Antibacterianos/imunologia , Formação de Anticorpos/imunologia , Síndromes de Imunodeficiência/imunologia , Polissacarídeos Bacterianos/imunologia , Salmonella typhi/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Adulto , Agamaglobulinemia/imunologia , Idoso , Imunodeficiência de Variável Comum/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Salmonella typhi/fisiologia , Febre Tifoide/imunologia , Febre Tifoide/microbiologia , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/administração & dosagem , Vacinação/métodos , Adulto JovemRESUMO
Toll-like receptors (TLRs) are key sensors of mycobacterial infections and play a crucial role in the initiation and coordination of the antimycobacterial innate immune response. T1805G, a functional TLR1 single nucleotide polymorphism (SNP), has been associated with susceptibility to pulmonary tuberculosis (PTB), but contradictory results among different populations have been reported. Our objective was to study this SNP in a genetically homogeneous population to evaluate its role in conferring susceptibility or resistance to PTB. In our population, the 1805G allele and the GG genotype (OR 2.04, 95%CI 1.26-3.31) influence susceptibility to PTB, in contrast with data observed in other populations.
Assuntos
Polimorfismo de Nucleotídeo Único , Receptor 1 Toll-Like/genética , Tuberculose Pulmonar/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Frequência do Gene , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Fatores de Risco , Espanha , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologiaRESUMO
BACKGROUND: The cytokine interleukin-6 (IL-6) is important in both immune responses and cardiovascular diseases. The IL-6 promoter polymorphism -174 G/C is associated with increased plasma concentrations of IL-6. The relationship between IL-6 polymorphisms and graft survival, cardiovascular events, and new-onset diabetes mellitus after kidney transplantation is controversial. OBJECTIVE: To analyze whether IL-6 (-174 G/C) polymorphism influences kidney graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes. METHODS: The IL-6 promoter polymorphism (-174 G/C) was analyzed using the polymerase chain reaction with sequence-specific primers in 335 kidney transplant recipients. Data for graft survival, chronic graft nephropathy, cardiovascular events, and new-onset diabetes were obtained retrospectively from clinical records. Categorical variables were compared between individuals with CC, GG, and GC genotypes using χ2 tests. Survival analysis was performed using the Kaplan-Meier method, comparing groups using the log-rank test. RESULTS: No significant differences were observed in 5-year graft survival between individuals with CC and GC/GG genotypes (85.3% vs 77.1%; P=.22). Nor were significant differences noted in the rates of chronic allograft nephropathy (37.5% vs 33.8%; P=.48), cardiovascular events (10.0% vs 23.0%; P=.10), or new-onset diabetes (7.5% vs 11.8%; P=.28). CONCLUSION: There is no association between IL-6 (-174 G/C) polymorphism and graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.
Assuntos
Sobrevivência de Enxerto , Interleucina-6/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , HumanosRESUMO
OBJECTIVE: To study whether two functional single nucleotide polymorphisms of the CC chemokine ligand 5 (CCL5) gene could affect susceptibility to pulmonary tuberculosis (TB) in a human immunodeficiency virus negative genetically homogeneous population, containing newly diagnosed patients with active disease. DESIGN: Seventy-six patients with active pulmonary TB (PTB) and 157 healthy control subjects from Cantabria, northern Spain, were genotyped for the CCL5 -403G/A and -28C/G polymorphisms. RESULTS: The frequency of the CCL5-403G/A and -28C/G promoter polymorphisms were significantly different between patients with active TB and control subjects. Three of the four possible haplotypes were also significantly different. The G/G-C/C diplotype was much more frequent in the healthy control group and the G/G-G/G and A/A-C/C diplotypes were more frequent in patients with PTB. CONCLUSION: Our findings indicate that CCL5 may play a role in conferring susceptibility to active PTB. Thus, the -403G and -28C alleles, either separately or combined in the G-C haplotype and the GG/CC diplotype, may be related to protection against PTB. By contrast, the -403A and -28G alleles, the G-G or A-C haplotypes and the G/G-G/G and A/A-C/C diplotypes may confer susceptibility to PTB.
Assuntos
Quimiocina CCL5/genética , Predisposição Genética para Doença/genética , Tuberculose Pulmonar/genética , Alelos , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Espanha , População BrancaRESUMO
Because a profound dysregulation of the immune system occurs in primary immunodeficiencies, viral infections are not uncommon. Human herpesvirus (HHV)-8 DNA was detected by polymerase chain reaction (PCR) analysis, Southern blotting, and in situ hybridization (ISH) in peripheral blood mononuclear cells and lymphoid organs (bone marrow, spleen, and lymph nodes) and endothelial and epithelial cells and macrophages from several organs (skin, lung, esophagus, intestine, choroid plexus [but not in brain or cerebellum], heart, striated muscle, liver, and kidney) of a human immunodeficiency virus-negative infant with DiGeorge anomaly who died of disseminated infection. Epstein-Barr virus DNA sequences were detected in the spleen and lymph nodes (by PCR and ISH) and in bone marrow (only by ISH) but not in blood or nonlymphoid organs. This report is believed to be the first of multiorgan dissemination of HHV-8 in a primary immunodeficiency.
Assuntos
DNA Viral/análise , Síndrome de DiGeorge/complicações , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Infecções Oportunistas/complicações , Southern Blotting , DNA Viral/genética , Endotélio/citologia , Endotélio/virologia , Células Epiteliais/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Soronegatividade para HIV , Infecções por Herpesviridae/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 8/genética , Humanos , Hibridização In Situ , Recém-Nascido , Leucócitos Mononucleares/virologia , Tecido Linfoide/virologia , Macrófagos/virologia , Infecções Oportunistas/virologia , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
We describe a girl with DiGeorge anomaly and normal cytogenetic and molecular studies, whose clinical course was complicated by graft versus host disease caused by intrauterine materno-fetal transfusion, and several immunohematological alterations including a monoclonal gammapathy of undetermined significance (first IgG, which subsequently changed to IgM). The main clinical features and pathological findings are discussed.
Assuntos
Síndrome de DiGeorge/complicações , Transfusão Feto-Materna/complicações , Doença Enxerto-Hospedeiro/complicações , Linfócitos T/imunologia , Pré-Escolar , Quimera , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/imunologia , Evolução Fatal , Feminino , Transfusão Feto-Materna/genética , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Linhagem , GravidezRESUMO
OBJECTIVE: To describe one case of symptomatic skin and pleural Kaposi sarcoma (KS) associated with kidney transplantation. Diagnosis was supported by morphologic study and human herpesvirus 8 (HHV-8) detection in both tissues. Pulmonary involvement was not present. DESIGN: The presence of HHV-8 DNA sequences was proved using polymerase chain reaction (PCR), Southern blot hybridization, and in situ hybridization. SETTING: Human herpesvirus 8 is found in most KS from patients with and without the acquired immunodeficiency syndrome. Clinically significant pulmonary infiltration by KS is diagnosed uncommonly antemortem, and pleural disease is exceptional. PATIENT: A 49-year-old man who had renal transplant with immunosuppressive therapy (tacrolimus and prednisone) and developed a cutaneous KS. A pleural effusion appeared without pulmonary involvement. Both lesions disappeared when immunosuppressive drugs were suspended. Later, the pleural effusion and the cutaneous lesions reappeared. Pleural biopsy specimens showed KS infiltration. OUTCOME: The patient refused treatment and was lost to follow-up. RESULTS: The skin and pleural biopsies showed a proliferation of spindle-shaped cells positive for CD34. The HHV-8 sequences were detected by nested PCR. No amplification was detected in uninvolved skin from the patient or in peripheral blood mononuclear cells from 10 healthy individuals used as controls. The Southern blot hybridization confirmed these results. CONCLUSIONS: To our knowledge, this is the first report of HHV-8 in symptomatic pleural KS, which was probably associated with immunosuppression after kidney transplantation. The demonstration of HHV-8 DNA in biopsy material in the appropriate cells could be diagnostic when the morphologic setting is consistent with KS.
Assuntos
DNA Viral/análise , Herpesvirus Humano 8/genética , Terapia de Imunossupressão/efeitos adversos , Transplante de Rim , Neoplasias Pleurais/virologia , Sarcoma de Kaposi/virologia , Southern Blotting , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Reação em Cadeia da Polimerase , Sarcoma de Kaposi/etiologia , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologiaRESUMO
HLA class II genes were analyzed to study IDDM susceptibility in Cantabria (Northern Spain). Patients showed highly significant increases in DRB1*0301 (RR = 4.581, p < 0.00005), DRB1*0401 (RR = 2.6, p < 0.05), DRB1*0402 (RR = 8.78, p < 0.05) and DRB1*0405 (RR = 14.73, p < 0.005). Highly significant diferences were in the DQA1*0301 (RR = 3.62, p < 0.000005) and DQA1*0501 (RR = 2.13, p < 0.05) alleles. DQB*0201 (RR = 4.1, p < 0.00005) and DQB1*0302 (RR = 5.42, p < 0.000005) alleles were also significantly increased. A significant increase in DRB1*0402-DQA1*0301-DQB1*0302 (RR = 16.18, p < 0.05), DRB1*0405-DQA1*0301-DQB1*0302 (RR = 16.12, p < 0.05), DRB1*0301-DQA1*0501-DQB1*0201 (RR = 4.58, p < 0.00005) and DRB1*0401-DQA1*0301-DQB1*0302 (RR = 4.36, p < 0.005) was apparent in the diabetic group, while the DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1401-DQA *0104-DQB1*05031 protective haplotypes (RR = 0.17 and 0.09, p < 0.0005 and 0.05, respectively) were significantly lower in patients. The absence of Asp57 and the presence of Arg52 were associated with disease in a dose-dependent manner. Several genotypes encoding the identical DQalpha52/DQbeta57 phenotype carried very different RRs. Finally, the Cantabrian population has the highest incidence of IDDM reported for Spain (15.2 of 100.000 in the 0-14 age group, Poisson's 95% CI: 10.6-19.3).
Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe II/genética , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Ligação Genética , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Teste de Histocompatibilidade , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Espanha/epidemiologia , População Branca/genéticaRESUMO
BACKGROUND: Hereditary angioneurotic edema (HANE) is an autosomal dominant disease due to genetic alterations at the C1 inhibitor gene. Mutations within the C1 inhibitor gene are responsible for the molecular defect in type II HANE. Most of the dysfunctional proteins result from mutations involving the Arg-444 (the P-1 site of the reactive center) or amino acids NH2-terminal to the reactive center. MATERIALS AND METHODS: We have studied a Spanish family with type II HANE by using polymerase chain reaction (PCR) to amplify the exon eight of the C1 inhibitor gene. The purified 338-bp PCR product was subcloned and transformed into competent cells. After overnight cultures, we extracted the cloning vector from the positive colonies and sequenced both strands of the PCR product from each patient and healthy members of the family. RESULTS: We show that affected individuals in this family have a missense mutation, changing an adenine to cytosine in the codon 445. This substitution changes threonine at the P-1' site of the reactive center to a proline. This mutation generates a new restriction site, recognized by Bsi YI. CONCLUSIONS: To our knowledge, this is the first molecular defect characterized in a Spanish family with type II HANE, and to date, this is the first reported mutation at the P-1' site of the reactive center in individuals with type II HANE. This new mutation located at the reactive center emphasizes once more time the enormous heterogeneity of this gene.