RESUMO
The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-ß (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-ß and IFN-γ levels.
Assuntos
Artrite Infecciosa/virologia , Citocinas/metabolismo , Infecções por Deltaretrovirus/virologia , Deltaretrovirus/fisiologia , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Alelos , Artrite Infecciosa/genética , Artrite Infecciosa/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Infecções por Deltaretrovirus/genética , Infecções por Deltaretrovirus/metabolismo , Feminino , Frequência do Gene , Genótipo , Haplótipos , Interações Hospedeiro-Patógeno , Humanos , Interferon gama/metabolismo , Interferons , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Contagem de Linfócitos , Masculino , Células Th1/metabolismo , Células Th2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Carga ViralRESUMO
About 95% of HTLV-1 infected patients remain asymptomatic throughout life, and the risk factors associated with the development of related diseases, such as HAM/TSP and ATL, are not fully understood. The human leukocyte antigen-G molecule (HLA-G), a nonclassical HLA class I molecule encoded by MHC, is expressed in several pathological conditions, including viral infection, and is related to immunosuppressive effects that allow the virus-infected cells to escape the antiviral defense of the host. The 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene influences the stability of the transcripts and could be related to HTLV-1-infected cell protection and to the increase of proviral load. The present study analyzed by conventional PCR the 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene in 150 unrelated healthy subjects, 82 HTLV-1 infected patients with symptoms (33 ATL and 49 HAM), and 56 asymptomatic HTLV-1 infected patients (HAC). In addition, the proviral load was determined by quantitative real-time PCR in all infected groups and correlated with 14-bp insertion/deletion genotypes. The heterozygote genotype frequencies were significantly higher in HAM, in the symptomatic group, and in infected patients compared to control (p < 0.05). The proviral load was higher in the symptomatic group than the HAC group (p < 0.0005). The comparison of proviral load and genotypes showed that -14-bp/-14-bp genotype had a higher proviral load than +14-bp/-14-bp and +14-bp/+14-bp genotypes. Although HLA-G 14-bp polymorphism does not appear to be associated with HTLV-1 related disease development, it could be a genetic risk factor for susceptibility to infection.
Assuntos
Infecções por Deltaretrovirus/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Mutação INDEL , Polimorfismo Genético , Adolescente , Adulto , Idoso , DNA Viral/genética , Suscetibilidade a Doenças , Feminino , Genótipo , Antígenos HLA-G , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Carga Viral/genéticaRESUMO
Fifteen patients with adult T-cell leukemia/lymphoma (ATLL) were identified in less than a two-year period in the Crown Heights-Bedford Stuyvesant section of Brooklyn, NY. All patients were black; nine patients originated from the Caribbean islands and six from the southern United States. Two of the patients were father and daughter, the first evidence of familial occurrence in the United States. Their clinical course was similar to that of previously described patients with this disorder. To our knowledge, these 15 patients represent the largest series of ATLL reported in the United States. We recommend that ATLL be seriously considered in the differential diagnosis of patients with non-Hodgkin's lymphoma, mycosis fungoides, lymphatic leukemia, or hypercalcemia.
Assuntos
Infecções por Deltaretrovirus/diagnóstico , Adulto , Idoso , População Negra , Infecções por Deltaretrovirus/etnologia , Infecções por Deltaretrovirus/genética , Diagnóstico Diferencial , Feminino , Humanos , Leucemia Linfoide/diagnóstico , Linfoma não Hodgkin/diagnóstico , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Estudos Retrospectivos , Estados Unidos , Índias Ocidentais/etnologiaRESUMO
The clinical syndrome earlier designated as paraparesia espástica del Pacífico is an isolated form of tropical spastic paraparesis (TSP) that was reported in 1981 in the southern Pacific lowlands of Columbia in and near Tumaco. The clinical features are similar to those of TSP reported in Jamaica, Martinique, the Seychelles, and the Ivory Coast of Africa and resemble also those clinical features of the human T-lymphotropic virus type I (HTLV-I)-associated myelopathy described in southern Japan. Since HTLV-I infection is closely associated with TSP, we conducted a case-control study to evaluate the role of HTLV-I-associated risk factors among patients from the endemic focus in Tumaco, Colombia, and the seroprevalence rates of this virus in other geographical areas of the Pacific Colombian lowlands with and without TSP. From our seroprevalence study of antibodies to HTLV-I among TSP index patients, matched controls, household contacts (first- and second-degree relatives), and healthy controls from these areas, we found a strong association between HTLV-I and TSP. Also, there is a high seroprevalence of HTLV-I among sexual partners of patients and to a lesser extent among their offspring and other relatives some of whom had an early mean acquisition of antibodies to HTLV-I. Heterosexual promiscuity and other close interpersonal contact may play an important role in the transmission of TSP in the Pacific lowlands of Colombia.