Lymphocyte subsets in Chediak-Higashi patients.

Peripheral blood lymphocyte subsets were studied in 6 Chediak-Higashi patients and 12 family members. The lymphocyte subsets were characterized by monoclonal antibody reagents and fluorescence flow-cytometry. An increase in OKT8 (suppressor/cytotoxic) and a decrease in OKT4 (helper) cell populations was observed in all patients studied. No correlation was seen between the clinical status (presence or absence of the lymphoproliferative phase) and the percentage of the lymphocyte subsets. The patient's mothers also had an increased percentage of OKT8-positive cells. The significance of these findings is discussed regarding the patients clinical course.

Reactivity of antiserum to human brain with peripheral blood lymphocytes.

Antisera to human brain (AHBS) and human thymocytes (AHTS) were produced in rabbits and selectively absorbed to render them specific for T cells. After absorption AHBS, but not AHTS, lost most of its cytotoxic activity against T cells. Absorbed AHBS bound up to 95% of peripheral blood T lymphocytes as detected by indirect immunofluorescence and inhibited up to 46% of the lytic activity of AHTS; however, it was incapable of inhibiting the E-rosette formation of T lymphocytes. All 10 samples of human peripheral blood lymphocytes, pretreated with AHBS, were significantly suppressed in their response to antigens, but fewer samples were affected in their response to mitogens and to allogeneic stimulation, indicating diversity in the nature of the receptors involved in the cellular responses.

Elevated antibody titers to Epstein-Barr virus and low natural killer cell activity in patients with Chediak-Higashi syndrome.

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.

Chediak-Higashi syndrome: immunological responses to Epstein-Barr virus studies in gene heterozygotes.

Immunologic studies were performed in five fathers and nine mothers of patients with Chediak-Higashi Syndrome (CHS). Antibody response to Epstein-Barr virus capsid antigen was higher than in normal controls. Antibodies to diffuse component of the early antigen were not detected and serum antibodies to the restricted component of the early antigen were observed in 64% of the subjects studied. Low natural killer activity and increased proportions of OKT8 positive cells were increased. These data indicate that immunologic alterations similar to those seen in CHS patients can be observed in their asymptomatic parents.

Chédiak-Higashi syndrome in a Venezuelan black child.

One case of Chédiak-Higashi syndrome (CHS) in a black male child, born to a consanguineous couple from a rural village in the State of Falcón, is described. At birth the child had marked skin depigmentation and ash-gray hair. A few months later he developed an almost normal black skin color. The diagnosis of CHS was established by the presence of large peroxidase-positive granules in his leukocytes. Neutrophils showed decreased chemotaxis and lack of digestive capacity against Candida albicans. Unusual features included extreme rarity of CHS in blacks, progressive repigmentation of the skin, and an early benign evolution. A high consanguinity index in the village from which this patient originated raised the possibility of the presence of a new cluster of this disease in Venezuela.

Hemoglobin Hofu associated with beta 0-thalassemia.

A mild anemia (hemoglobin 9 g/dl) was found in a patient from Seville (Spain) with marked morphological abnormalities in the peripheral blood smear. The red cell osmotic fragility showed a mild resistance curve with a mean cell fragility (MCF) of 0.375% NaCl (normal = 0.450). Chemical Chemical and thermal instability test and search for inclusion bodies gave positive results. Hemoglobin electrophoresis at pH 8.9 revealed absence of Hb A, a major component of fast mobility (94%), and increased Hb F and Hb A2 levels (1.5% and 4.6%, respectively). The fast fraction, isolated and purified by means of cellulose acetate electrophoresis, precipitated in acid acetone and treated with urea 8 M and mercaptoethanol, revealed an anomalous beta chain. Trypsin-digested globin peptides were separated by high-voltage electrophoresis at pH 6.4 and ascendant chromatography. With differential staining, an extra peptide was detected in an unusual site, more anodic than alpha Tp4 but in lower position. Peptide map of the fast beta chain, stained with ninhydrin, and also for Tyr, confirmed the position of the new peptide and the absence of the usual beta Tp13. The new peptide, separated by high-voltage electrophoresis at pH 3.5, revealed absence of Val and the presence of an additional Glu residue, which should appear only in position beta 126. The diagnosis of Hb Hofu (alpha 2 beta 2 126 Val----Glu; H4) was reached, thus interpreting its increase and the absence of Hb A, as an association with beta o-thalassemia, producing a mild hemolytic anemia. Evidence was obtained that Hb Hofu is a mild unstable hemoglobin variant.

Caracteristicas hematologicas de la poblacion del Estado Falcon (Venezuela). I. Variantes hemoglobinicas, antigeno Australia y niveles de immunoglobulinas. / Hematologic characteristics of the population of the Falcon State (Venezuela). I. Hemoglobin variants, Australian antigen and immunoglobulin levels

Se estudio 501 donantes voluntarios del Banco de Sangre del Hospital Alfredo van Grieken de Coro en cuanto a variantes o alteraciones hemoglobinicas, antigeno Australia y niveles de inmunoglobulinas. Los grupos sanguineos ABO y Rh mostraron una distribucion que puede considerarse caracteristica para la poblacion venezolana. Se encontro 2,40% con valores aumentados de Hb F, 2,99% con valores moderadamente aumentados de HbA2, 0,40% con valores francamente aumentados de A2, 3,79 de Hb AS, 0,80% de Hb AC y 0,20% de Hb AD Punjab, lo cual indica que en el estado Falcon de cada 11 sujetos 1 tiene alguna variante o alteracion hemoglobinica. Estos resultados representan la intensa mezcla racial que viene operandose en el estado desde la epoca del descubrimiento, habiendose encontrado variantes hemoglobinicas prevalentes en africanos y espanoles. El antigeno Australia, estudiado en 300 donantes, mostro una positividad del 2,33%, que es mayor que la encontrada en Caracas.Los niveles de inmunoglobulinas A, G y M, determinadas en 25 donantes, resultaron un poco mas altos que los obtenidos en donantes de Caracas

Sindrome de Chediak-Higashi en un infante de raza negra. / Chediak-Higashi syndrome in a negroid race infant

El sindrome de Chediak-Higashi es una rara condicion autosomica recesiva. Ninguno de los casos descritos previamente era de raza negra. La observada consanguinidad en los padres de nuestro paciente, ha sido igualmente demostrada en la mitad de los casos. Sin embargo, en los casos previamente reportados, fue raramente observada la consanguinidad. El estudio de la pequena poblacion rural donde los padres nacieron revelo evidencia preliminar de un alto indice de consanguinidad. Esto lleva a la posibilidad que nuevos casos de este sindrome puedan ser encontrados y que esta poblacion pueda constituirse en el segundo foco de esta enfermedad en Venezuela

Leucemias en Venezuela asociadas al virus humano de leucemia/linfoma tipo I (HTLV-1) / Human T cells leukaemia/limphoma virus type I (HTLV-1) associated leukaemias in Venezuela

Se describen 5 casos de leucemias positivas para el virus humano de leucemia/linfoma tipo I (HTLV-1). Tres de los pacientes eran nativos de una región de alta endemicidad para este virus, (Estado Zulia, Venezuela) y padecían de leucemia aguda linfoblástica o indiferenciada. Los otros dos pacientes eran originarios de una zona de baja endemicidad (Caracas), con leucemia linfocítica crónica y promielocítica aguda. El estudio de los marcadores de superficie celular no mostró evidencia de un fenotipo de leucemia de célula T del adulto en ningún caso y sugiere que la infección por HTLV-1 puede estar asociada con desórdenes proliferativos no T. Alternativamente HTLV-1 puede ser el agente etiológico de una variedad de formas de leucemias, específicamente en las áreas de alta endemicidad en el Caribe