RESUMO
Endemic Chediak-Higashi Syndrome occurs in a restricted geographic area (Pregonero, State of Táchira, Venezuela). Neutrophils from these patients were unable to digest Candida albicans in vitro, but showed normal or increased metabolic activities. This finding supports the view that the endemic syndrome is bona fide Chediak-Higashi Syndrome.
Assuntos
Síndrome de Chediak-Higashi/fisiopatologia , Neutrófilos/fisiologia , Síndrome de Chediak-Higashi/genética , Humanos , Valores de Referência , VenezuelaRESUMO
Four Venezuelan patients with the autosomal recessive Chediak-Higashi syndrome (CHS) were studied. The results confirm the severe reduction in natural killer (NK) cell activity, as previously described and showed also a decline in the activity of cells involved in antibody-dependent cellular cytotoxicity (ADCC). No defect was found in the production of immunoglobulins and of specific antibodies to measles, varicella, herpes simplex, and cytomegalo viruses. Two of the patients had extremely high antibody titers to the Epstein-Barr virus (EBV) specific viral capsid antigen (VCA), to the restricted (R) component of the EBV-induced early antigen complex, and to the EBV-associated nuclear antigen (EBNA). These two patients had enlarged livers, spleens, and lymph nodes indicative of the lymphoproliferative phase. The other two patients were initially negative for all EBV-associated antibodies but seroconverted subsequently and, in the course of a year, also developed high antibody titers to VCA and R. In one of these patients the primary infection was accompanied by moderate signs of infectious mononucleosis (IM) followed after more than 6 months by persistent hepatosplenomegaly. The other patient also developed signs of a lymphoproliferative syndrome with hepatosplenomegaly and jaundice and died 8 months later. Such high anti-R titers are seen frequently in Burkitt's lymphoma, but rarely in other conditions. It is likely that the high antibody titers reflect an increased production of VCA and R due to defective NK and ADCC cell activities so that productively infected B lymphocytes are no longer eliminated before they have synthesized maximal amounts of antigens. The high anti-EBNA titers suggest normal T lymphocyte function. The possibility that the accelerated, lymphoma-like phase of the CHS involves EBV-transformed cells is discussed.
Assuntos
Anticorpos Antivirais/biossíntese , Síndrome de Chediak-Higashi/imunologia , Infecções por Herpesviridae/imunologia , Células Matadoras Naturais/imunologia , Adulto , Anticorpos Antivirais/análise , Citotoxicidade Celular Dependente de Anticorpos , Proteínas Sanguíneas/análise , Síndrome de Chediak-Higashi/complicações , Síndrome de Chediak-Higashi/epidemiologia , Pré-Escolar , Citotoxicidade Imunológica , Feminino , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4/imunologia , Humanos , Imunidade Celular , Lactente , Masculino , VenezuelaRESUMO
Fourteen cases of the Chediak-Higashi syndrome found in twelve non-related families living in a defined geographical area not larger than 200 km2 of the Tachira State, Venezuela (population of around 72,000 inhabitants) were diagnosed between 1967 and 1974. The patients were pre-school or nursing age children except one eleven year old female. Six of the patients were male. All showed the same typical somatic characteristics of this syndrome. Four cases were 2 pairs of brothers. Consanguinity of the parents was seen in only two families, even though the majority of them come from the same restricted geographic zone (Pregonero). Since this anomaly is supposedly produced by a rare recessive autosomal gene, the existence of its high frequency in a small Venezuelan region may be explained through the "founder effect" in a population with a high inbreeding coefficient.