Leche materna: características funcionales de los oligosacáridos de la leche materna (Parte 2) / Breast milk: functional characteristics of breast milk oligosaccharides (Part 2)

Durante los primeros meses de vida, los oligosacáridos de la leche materna (HMOs) aportados por la leche materna participan en procesos asociados con la maduración de tejidos y sistemas del tubo digestivo, modulan algunos de sus procesos metabólicos y ejercen efectos prebióticos y antimicrobianos. Otros efectos estudiados son su contribución a la instalación, desarrollo y estimulación de la microbiota residente con predomino de Bifidobacterium y Bacteroides, con efectos protectores frente a posibles colonizaciones o patologías por enteropatógenos (bacterianas, virus o parásitarias) que pueden actuar nivel local en el tubo digestivo, pero también pueden influir a nivel sistémico. Los HMOs modularían el desarrollo de la inmunidad innata y adaptativa, y probablemente previenen el desarrollo de fenómenos de atopia/alergia. Una patología propia de la etapa neonatal de los prematuros es la enterocolitis necrosante y algunos HMOs podrían disminuir el riesgo de su manifestación. Las actividades de los oligosacáridos de la leche materna contribuyen a la adaptación del lactante a los desafíos que plantea su entorno incluyendo la prevención de algunas patologías en edades posteriores, como es el caso de la diabetes tipo 1 y la obesidad.

During the first months of life, breast milk oligosaccharides (HMOs) stimulate development of the gastrointestinal tract in newborns and young infants; they modulate its metabolism and transport capabilities. Additionally, they exert prebiotic and antimicrobial activities and contribute to the development of the resident intestinal microbiota with a predominance of Bifidobacterium and Bacteroides and protect from colonization and infections by enteropathogens (bacteria, virus or parasites). It is highly probable that their activities extend beyond infancy and persist into adult life. HMOs stimulate the development of the innate and adaptive immune systems and decrease the risk of atopy/allergy. Their intake has been associated with a degree of protection against as necrotizing enterocolitis among premature infants. HMOs contribute to the long term adaptation and protection of newborn infants to unfavorable conditions of their environment and in this way may contribute to protect breastfed infants from type 1 diabetes and obesity.

Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling

Oligosaccharides are implicated in the development of the immune response notably in complement activation. Anti-tumoural immunotherapy by monoclonal antibodies (mAbs) offers some advantages to chemotherapy including cell targeting but some of them are inefficient to generate cytotoxicity dependent complement (CDC) known to be important in the antibody’s efficacy. The aim of this study is to give a CDC activity of mAb by linkage of a complement activating oligosaccharide to this antibody via a hetero-bifunctional linker allowing control of the conjugation reaction. We worked on non Hodgkin Burkitt’s lymphoma as cancer source, Fab fragments of rituximab devoid of complement activity as mAb and the trisaccharide Gal alpha(1→3)Gal beta(1→4)GlcNAc as immunogenic glycan. The bioconjugate Fab-Gal was characterized by biochemical methods and we demonstrated that the α-Gal epitope was recognized by seric immunoglobulins. After checking the recognition capacity of the Fab-Gal conjugate for the CD20 epitope, in vitro assays were performed to evaluate the activation of the complement cascade by the Fab-Gal conjugate. The effect of this bioconjugate was confirmed by the evaluation of the proliferation response of Burkitt’s cell line. The relative facility realization of this strategy represents new approaches to increase activities of mAbs.

Características serológicas y análisis inmunohistológico del anticuerpo monoclonal IHI-15 ANTI-A: resultados de su evaluacion en Nantes / Serological characteristics and immnunohistological analysis of the IHI-15 anti-A monoclonal antibody: results of the evaluation at Nantes

Se revisan los resultados de la evaluación del anticuerpo monoclonal IHI-15 anti-A en el III Taller/Simposio Internacional de Anticuerpos Monoclonales contra Antígenos de Grupos Sanguíneos y Relacionados efectuado en Nantes, Francia. El IHI-15 es una molécula de IgM que aglutina a los eritrocitos humanos que expresan al antígeno A del sistema ABO. Se comprobó su especificidad, avidez, título y potencia por distintos métodos de hemaglutinación frente a los principales subgrupos de A y frente a las variantes débiles. En el método de hemaglutinación por centrifugación en microplacas reaccionó con una muestra de la variante Ax y otras débiles (A3 y A2B) con un título mayor que otros de referencia. Su reactividad inmunohistológica lo identifica con los anticuerpos dirigidos contra estructura A tipo 3/4 porque marca preferentemente a las células epiteliales en la mucosa pilórica y duodenal de secretores A en el área del aparato de Golgi. No reaccionó por ELISA con los trisacáridos A, ni tetrasacáridos A tipo 1 sintéticos. El IHI-15 anti-A es la base del reactivo hemoclasificador Hemo-CIM anti-A que cumple con las especificaciones de la OMS para los métodos de hemaglutinación por centrifugación en tubos y láminas portaobjeto, que comercializa CIMAB, S.A

Antibody response of Mexican infants to Haemophilus influenzae type b capsular polyribosylribitol phosphate. Differences between natural and vaccine induced (Oligosaccharide-CRM197 conjugated vaccine) immunization

In this study we compared natural vs induced Haemophilus influenzae type b (hib) anti-capsular polyribosylribitol phosphate (PRP) antibody response in a low socioeconomic population. One hundred twenty five 2-month-old children received the complete HbOC vaccine immunization scheme and a boster dose at 15 month of age. One hundred twenty five non-immunized children served as the control group. Serum Hib anti-PRP antibody titers were determuined by ELISA in all children. We found at the end of the primary immunization scheme an antibody concentration of 27.28 µg/ml in the immunized group vs. 7.48 µg/ml in the control group. The antibody response was mainly of the IgG1 class in both groups. After the booster dose the antibody concentration was 30.14 g/ml in the vaccinated group vs. 6.06 µg/ml in the control group (p<0.01). Ninety nine percent of immunized and non-immunized infants had titers greater than 1 µg/ml. These results confirm that immunization with the HbOC vaccine induces an important increase in anti-PRP specific antibody titer, but they also demonstrate that natural exposure induces responses higher than those referred as protective (1 µg/ml)