Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia.

Plasmodium species, the parasitic agents of malaria, invade erythrocytes to reproduce, resulting in erythrocyte loss. However, a greater loss is caused by the elimination of uninfected erythrocytes, sometimes long after infection has been cleared. Using a mouse model, we found that Plasmodium infection induces the generation of anti-self antibodies that bind to the surface of uninfected erythrocytes from infected, but not uninfected, mice. These antibodies recognize phosphatidylserine, which is exposed on the surface of a fraction of uninfected erythrocytes during malaria. We find that phosphatidylserine-exposing erythrocytes are reticulocytes expressing high levels of CD47, a "do-not-eat-me" signal, but the binding of anti-phosphatidylserine antibodies mediates their phagocytosis, contributing to anemia. In human patients with late postmalarial anemia, we found a strong inverse correlation between the levels of anti-phosphatidylserine antibodies and plasma hemoglobin, suggesting a similar role in humans. Inhibition of this pathway may be exploited for treating malarial anemia.

[Mutations of resistance of HIV-1 in previously untreated patients at penitentiary centers of the Autonomous Community of Valencia, Spain. REPRICOVA study]. / Mutaciones de resistencia de virus de la inmunodeficiencia humana tipo 1 en pacientes no tratados de los centros penitenciarios de la Comunidad Valenciana. Estudio REPRICOVA.

BACKGROUND: Our purpose was to determine the prevalence of mutations of resistance to nucleoside inhibitors of reverse transcriptase (NIRT) and protease inhibitors (PI) in the HIV-1 genotype of naïve infected subjects in the prisons of the Autonomous Community of Valencia, Spain. PATIENTS AND METHOD: Multicentric, descriptive, cross-sectional study of prevalence including a systematic stratified and randomised sampling by centres. Demographic, clinical, virological and immunological data were collected. The HIV gene of protease and transcriptase was studied in peripheral blood plasma samples by means of double PCR amplification and subsequent automatic sequence. Reference: wild strain HXB2. RESULTS: Plasma was obtained from 133 individuals (119 men and 14 women). 117 samples were selected and the rest did not have enough copies for transcription. With regard to NIRT, 7 samples (5.2% of total) showed some mutation of resistance: M41L, D67N, L210W and K219Q, all them secondary to and associated with resistance to zidovudine, abacavir as well as group B multinucleoside-resistance. With regard to PI, only one sample showed a primary mutation, M46I, which was associated with resistance to indinavir. Moreover, a further 41 samples were found to express some secondary mutation. CONCLUSIONS: In our series, there was a low number of primary mutations of resistance. These results allow us to exclude the systematic use of resistance tests before an initiation antiretroviral therapy.

[Epidemiology of Paget's disease. Peculiarities in the province of Zamora]. / Epidemiología de la enfermedad de Paget. Peculiaridades en la provincia de Zamora.

BACKGROUND: Some paramyxovirus (measles, respiratory syncytial virus, and dog's distemper virus) are currently considered to be responsible for Paget's disease of the bone. A relevant role is also given to inheritance as predisposing factor. Some authors have found an association between HLA antigens with this disease, but without unanimous agreement. Although this hypothesis of an interaction between a genetic factor and a viral infectious agent is the most accepted universally, there is not yet a definitive cause for the disease. The participation of some other environmental factors has not been ruled out. METHODS: One hundred and forty patients in the Zamora province were studied. The geographic distribution in the different areas of the province was analyzed and also whether there was family aggregation all cases. HLA-I was determined in 59 patients and HLA-II in cases with aggregation. The mineral composition (calcium, fluorine, magnesium, nitrates, and chlorine) analysis of public running water was carried out in all population centers in the province. RESULTS: Aggregation was found in four families (four, two, four, and three siblings, respectively). Although HLA-I antigens were determined in 59 patients, no association was found. HLA-II antigens were also determined in the involved patients with family links and no association was found between these antigens and the disease. A much higher aggregation was found in some particular areas in our province and these foci coincided with some characteristics of mineral composition of public running waters. CONCLUSIONS: There is a genetic factor predisposing to the disease, as family aggregation occurs with a higher frequency than would otherwise be expected. Nevertheless, no association with HLA antigens was found. This disease is more common in some particular geographic areas, thus supporting the hypothesis of an environmental factor as trigger. An association was found between mineral composition of public running waters and patient geographic distribution.

Las vacunas hexavalentes: una realidad en el futuro de la vacunación / Hexavalent vaccines: a fact in vaccination future

Las vacunas hexavalentes combinan antígenos frente a seis enfermedades en una unidad de administración simple. Esto conlleva múltiples ventajas: vacunación contra polio con VPI, vacunación con Pa (Pertussis acelular), reducción del número de inyecciones, mejora de coberturas de vacunación, simplificación de los programas de vacunación, posibilidad de reducción de los costes de los programas de vacunación y mayor facilidad en el transporte y almacenaje. No obstante, las vacunas combinadas también deben superar una serie de problemas: la combinación debe ser estable, no debe haber interferencias inmunológicas, la eficacia, seguridad y tolerancia han de ser iguales o superiores a las vacunas monovalentes, los adyuvantes y excipientes no deben interferir con todos los antígenos y el volumen total a inyectar debe ser pequeño. Múltiples estudios han demostrado que las vacunas hexavalentes han superado estas dificultades. Se realiza una revisión sobre el uso de las vacunas hexavalentes (DTP-Hib-VPI-HB), analizando la conveniencia de la introducción de estas vacunas en los calendarios de vacunación (AU)

Mutaciones de resistencia de virus de la inmunodeficiencia humana tipo 1 en pacientes no tratados de los centros penitenciarios de la comunidad valenciana. estudio repricova / Mutations of resistance of HIV-1 in previously untreated patients at penitentiary centers of the Autonomous Community of Valencia, Spain. REPRICOVA study

FUNDAMENTO: Determinar la prevalencia de mutaciones de resistencia a inhibidores nucleósidos de la transcriptasa inversa (INTI) y a inhibidores de proteasas (IP) en el genoma del virus de la inmunodeficiencia humana tipo 1 de infectados no tratados de las prisiones de la Comunidad Valenciana. PACIENTES Y MÉTODO: Estudio multicéntrico, descriptivo, transversal de prevalencia en un día. Muestreo aleatorio, sistemático estratificado por centros. Se recogen variables demográficas, clínicas, virológicas e inmunológicas. Se estudia el gen de la proteasa y de la transcriptasa del VIH en muestras plasmáticas de sangre periférica mediante doble amplificación por reacción en cadena de la polimerasa y subsiguiente secuenciación automática. Secuencia de referencia: cepa salvaje HXB2. RESULTADOS: Se obtiene plasma de 133 individuos (119 varones y 14 mujeres). Se secuencian 117 muestras, ya que las restantes no tienen suficiente número de copias para ser transcritos. Respecto a INTI, 7 muestras (el 5,2 por ciento del total) presentaba alguna mutación de resistencia: M41L, D67N, L210W y K219Q, todas secundarias y asociadas a resistencia a zidovudina, abacavir y multirresistencia del grupo B. Respecto a IP, sólo una muestra expresa la primaria M46I asociada a resistencia a indinavir; otras 41 muestras expresan alguna mutación secundaria. CONCLUSIONES: En la serie analizada, hay un escaso número de mutaciones primarias de resistencia. Estos resultados permiten excluir la utilización sistemática de las pruebas de resistencia previas a la terapia antirretroviral de inicio (AU)