Publication: Producción y caracterización de extractos alergénicos polimerizados de alternaria alternata. Evaluación de su alergenicidad e inmunogenicidad
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2018-03-21
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Universidad Complutense de Madrid
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Abstract
Las enfermedades alérgicas suponen un importante problema de salud a nivel mundial debido a su creciente incidencia, elevada prevalencia y coste asistencial. Los hongos son la tercera causa más frecuente de patologías respiratorias y los más relacionados con un mal pronóstico del asma. Los géneros Alternaria y Cladosporium son los más frecuentemente relacionados con enfermedades respiratorias de tipo alérgico, siendo Alternaria el que presenta mayor prevalencia de sensibilización, sobretodo en el área Mediterránea. La inmunoterapia específica con alérgenos es el único tratamiento efectivo para la desensibilización alergénica y que puede cambiar la historia natural de la enfermedad. Sin embargo, no está exenta de riesgos. La vacunación con extractos alergénicos del hongo Alternaria alternata produce frecuentemente reacciones alérgicas en los pacientes tras su administración. Existen numerosos factores que influyen en la composición alergénica de los extractos que pueden comprometer la seguridad y eficacia de las vacunas. La modificación química de los alérgenos mediante su entrecruzamiento con glutaraldehído (polimerización) permite disminuir la alergenicidad de los extractos alergénicos sin comprometer su capacidad inmunogénica. La inmunoterapia específica con alérgenos polimerizados, ha demostrado ser eficaz en el tratamiento de enfermedades alérgicas producidas por pólenes, ácaros y epitelios de animales. Determinadas fuentes alergénicas presentan dificultades para polimerizar con glutaraldehído, como los alérgenos de A. alternata...
Allergic diseases represent an important global health problem due to their increasing incidence, high prevalence and cost of care. Fungi are the third most frequent cause of respiratory diseases and the most related to a poor prognosis of asthma. The genera Alternaria and Cladosporium are the most frequently related to allergic respiratory diseases, being Alternaria the most prevalent source of sensitization, especially in the Mediterranean area. Immunotherapy of allergic diseases is the only effective treatment for allergen desensitization and can change the natural history of the disease. However, it is not exempt of risks. Vaccination with Alternaria alternata allergenic extracts frequently produces allergic reactions in the patients, following its administration. Numerous factors influence the allergenic composition of the extracts which may compromise the safety and efficacy of the vaccines. Chemical modification of allergens by crosslinking with glutaraldehyde (polymerization), allows to reduce the allergenicity of the allergenic extracts without compromising their immunogenic capacity. Specific immunotherapy with polymerized allergens has been shown to be effective in the treatment of allergic diseases caused by pollens, mites and animal epithelia. Certain allergenic sources present difficulties to polymerize with glutaraldehyde, as is the case of A. alternata allergens. The main objective of this work was the production and characterization of allergenic extracts of A. alternata modified with glutaraldehyde with decreased allergenicity while maintaining its immunogenicity. To achieve it, it was necessary to optimize and standardize the methods of culture and the purification of allergens. The culture in a liquid medium provided a higher protein yield than in semisolid medium (a 33% increase)...
Allergic diseases represent an important global health problem due to their increasing incidence, high prevalence and cost of care. Fungi are the third most frequent cause of respiratory diseases and the most related to a poor prognosis of asthma. The genera Alternaria and Cladosporium are the most frequently related to allergic respiratory diseases, being Alternaria the most prevalent source of sensitization, especially in the Mediterranean area. Immunotherapy of allergic diseases is the only effective treatment for allergen desensitization and can change the natural history of the disease. However, it is not exempt of risks. Vaccination with Alternaria alternata allergenic extracts frequently produces allergic reactions in the patients, following its administration. Numerous factors influence the allergenic composition of the extracts which may compromise the safety and efficacy of the vaccines. Chemical modification of allergens by crosslinking with glutaraldehyde (polymerization), allows to reduce the allergenicity of the allergenic extracts without compromising their immunogenic capacity. Specific immunotherapy with polymerized allergens has been shown to be effective in the treatment of allergic diseases caused by pollens, mites and animal epithelia. Certain allergenic sources present difficulties to polymerize with glutaraldehyde, as is the case of A. alternata allergens. The main objective of this work was the production and characterization of allergenic extracts of A. alternata modified with glutaraldehyde with decreased allergenicity while maintaining its immunogenicity. To achieve it, it was necessary to optimize and standardize the methods of culture and the purification of allergens. The culture in a liquid medium provided a higher protein yield than in semisolid medium (a 33% increase)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Bioquímica y Biología Molecular III, leída el 18-05-2017