RESUMO
Three males with the X-linked lymphoproliferative syndrome (XLP) with hypo- or agammaglobulinemia following Epstein-Barr virus (EBV) infection and two males with the chronic mononucleosis syndrome were investigated for immune responses to EBV-determined antigens. Males with XLP showed profound cellular immune defects. Markedly diminished responses of natural killer cell and interferon-activated killer cell activities and impaired leukocyte migration inhibition responses to phytohemagglutinin were determined in patients with XLP. The two patients with chronic mononucleosis showed less severe defects. All patients showed partial or complete impairment of their EBV-specific immune responses as measured by leukocyte migration inhibition. EBV-specific antibodies were markedly diminished against EBV-associated nuclear antigen, early antigen, and viral capsid antigen in males with XLP. In contrast, patients with chronic mononucleosis had elevated antibodies to most EBV-specific antigens. Individuals with life-threatening EBV-induced lymphoproliferative disorders may exhibit multiple defective immune mechanisms against the virus.
Assuntos
Herpesvirus Humano 4/imunologia , Células Matadoras Naturais/imunologia , Transtornos Linfoproliferativos/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Agamaglobulinemia/imunologia , Animais , Anticorpos Antivirais/análise , Antígenos Virais/imunologia , Criança , Doença Crônica , Feminino , Ligação Genética , Humanos , Imunidade Celular , Imunidade Inata , Mononucleose Infecciosa/imunologia , Interferons/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Transtornos Linfoproliferativos/genética , Masculino , Linhagem , Infecções Tumorais por Vírus/imunologia , Cromossomo XRESUMO
We have analysed the prognostic influence of cytogenetic findings at diagnosis in a group of 502 children with acute lymphoblastic leukaemia (ALL), treated on MRC UKALL X, in whom clonal cytogenetic abnormalities were detected at diagnosis. Despite the overall improvement in outcome in children treated on this protocol compared with previous trials, some cytogenetically-defined groups were still associated with a poor outcome and ploidy retained some prognostic significance. Patients with high hyperdiploid ALL (39% of those with clonal abnormalities) had a favourable outcome with event free survival of 71% at 5 years. Those with near haploidy (1%), hypodiploidy (9%) and low hyperdiploidy (16.5%) had a relatively poor prognosis with event-free survival at 5 years of 17%, 42% and 49% respectively. Only two of 12 children with Ph-positive leukaemia are alive in remission and abnormalities of chromosome 11q23 were also associated with a high risk of treatment failure. In contrast, the t(1;19) was associated with improved event-free survival of 87.5% at 5 years. A number of other non-random abnormalities were identified with no clear prognostic significance. We conclude that identification of certain genetic changes remains important in the management of acute lymphoblastic leukaemia, although whether molecular diagnosis of clinically relevant abnormalities can now supplant cytogenetics in the clinical trials context remains to be determined.