RESUMEN
BACKGROUND: Kaposi's sarcoma-associated herpes virus is associated with primary effusion lymphoma and multicentric Castleman's disease. METHODS: Seropositivity to lytic and latent Kaposi's sarcoma herpes virus (KSHV) antigens were examined in 2083 lymphomas and 2013 controls from six European countries. RESULTS: Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and 3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds ratio (OR)=4.11, 95% confidence interval (CI)=1.57-10.83) and multiple myeloma (OR=0.31, 95% CI=0.11-0.85). CONCLUSION: The KSHV is unlikely to contribute importantly to lymphomagenesis among immunocompetent subjects. However, the observed association with SMZL may underline a chronic antigen mechanism in its aetiology.
Asunto(s)
Anticuerpos/inmunología , Antígenos Virales/inmunología , Herpesvirus Humano 8/inmunología , Linfoma no Hodgkin/inmunología , Sarcoma de Kaposi/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedad de Castleman/inmunología , Niño , Preescolar , Europa (Continente) , Femenino , Humanos , Lactante , Recién Nacido , Linfoma no Hodgkin/virología , Linfoma de Efusión Primaria/inmunología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
To investigate a possible association between human herpesvirus 8 (HHV-8) and prostate cancer, we evaluated HHV-8 seroprevalence in 2 case-control studies. HHV-8 antibodies were detected by immunofluorescence with cells expressing lytic viral proteins and by enzyme immunoassays with recombinant viral structural protein (K8.1) and latent protein (latency-associated nuclear antigen-1; open reading frame 73), respectively. HHV-8 seroprevalence tended to be lower in patients with prostate cancer than in control subjects, but there was no significant difference in either study. These data imply that HHV-8 is not a major prevalent cause of prostate cancer.
Asunto(s)
Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 8/patogenicidad , Neoplasias de la Próstata/virología , Adulto , Negro o Afroamericano , Anticuerpos Antivirales/análisis , Estudios de Casos y Controles , District of Columbia/epidemiología , Infecciones por Herpesviridae/epidemiología , Humanos , Italia/epidemiología , Masculino , Hiperplasia Prostática/virología , Estudios Seroepidemiológicos , Población BlancaRESUMEN
OBJECTIVE: To characterize immune phenotype and thymic function in HIV-1-infected adults with excellent virologic and poor immunologic responses to highly active antiretroviral therapy (HAART). METHODS: Cross-sectional study of patients with CD4 T cell rises of > or = 200 x 10(6) cells/l (CD4 responders; n = 10) or < 100 x 10(6) cells/l (poor responders; n = 12) in the first year of therapy. RESULTS: Poor responders were older than CD4 responders (46 versus 38 years; P < 0.01) and, before HAART, had higher CD4 cell counts (170 versus 35 x 106 cells/l; P = 0.11) and CD8 cell counts (780 versus 536 x 10(6) cells/l; P = 0.02). After a median of 160 weeks of therapy, CD4 responders had more circulating naive phenotype (CD45+CD62L+) CD4 cells (227 versus 44 x 10(6) cells/l; P = 0.001) and naive phenotype CD8 cells (487 versus 174 x 10(6) cells/l; P = 0.004) than did poor responders (after 130 weeks). Computed tomographic scans showed minimal thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P = 0.006). Poor responders had fewer CD4 cells containing T cell receptor excision circles (TREC) compared with CD4 responders (2.12 versus 27.5 x 10(6) cells/l; P = 0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P = 0.05). Metabolic labeling studies with deuterated glucose indicated that the lower frequency of TREC-containing lymphocytes in poor responders was not caused by accelerated proliferation kinetics. CONCLUSION: Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos/fisiología , Infecciones por VIH/tratamiento farmacológico , VIH-1/inmunología , Timo/fisiología , Adulto , Linfocitos T CD4-Positivos/inmunología , Femenino , Reordenamiento Génico de Linfocito T/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Subgrupos Linfocitarios , Masculino , Persona de Mediana Edad , Telómero/genética , Replicación ViralRESUMEN
Although treatment with combination antiretroviral therapy leads to a reduction in the level of plasma viremia and an improvement in CD4 T cell count for most patients, for a minority of patients, an improvement in CD4 T cell count occurs despite the failure of treatment to suppress viral replication. Recent reports suggest that these discordant improvements in CD4 T cell count may last for months to years and are associated with improved clinical outcomes. In a retrospective observational study, we evaluated the effect of therapy cessation on 8 patients with discordant immunologic responses to therapy and found that improved CD4 T cell responses are dependent upon ongoing drug pressure. If antiretroviral agents that are likely to resuppress the virus are not available, we suggest that patients continue the therapy associated with immunologic improvement to maximize the clinical benefit of the discordant response.