Gen regulador de autoinmunidad (AIRE) y desarrollo de tiroiditis autoinmune en síndrome de Down
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Palabras clave
Tiroiditis Autoinmune, Síndrome de Down, Trisomía, Gen Regulador de Autoinmunidad (AIRE)
Resumen
Introducción: el gen regulador de autoinmunidad (AIRE), codificado en el cromosoma 21, desempeña un papel central en la eliminación de linfocitos T autorreactivos mediante la selección negativa en el timo. En el síndrome de Down (SD), o trisomía 21, puede inducirse una sobreexpresión de AIRE, lo que se ha relacionado con una mayor prevalencia de enfermedades autoinmunes, como la tiroiditis autoinmune.
Objetivo: analizar las variantes genéticas del gen AIRE asociadas con autoinmunidad en personas con SD, así como los mecanismos epigenéticos y ambientales que pudieran modular su expresión y/o función.
Material y métodos: se realizó un análisis in silico de variantes genéticas y microARN reguladores de AIRE, mediante la revisión de tres plataformas bioinformáticas: Ensembl, ClinVar y miRBase. El procesamiento de datos y el análisis gráfico se llevaron a cabo en Excel (Office 365) y en lenguaje R versión 4.3.0 (Bell Laboratories, EUA).
Resultados: se identificaron 1,104 variantes del gen AIRE asociadas a enfermedades autoinmunes en Ensembl, y 162 variantes patogénicas o probablemente patogénicas en ClinVar. El 19.3 % de las variantes presentaron un potencial impacto funcional. Sin embargo, entre los microARN codificados en el cromosoma 21, no se identificó evidencia concluyente de regulación negativa directa sobre AIRE, salvo reportes preliminares in vitro del miR-155.
Conclusiones: la sobreexpresión de alelos de riesgo, la presencia de variantes estructurales y la regulación epigenética podrían explicar la disfunción de AIRE y la mayor prevalencia de tiroiditis autoinmune en personas con SD. Estos hallazgos respaldan la necesidad de realizar estudios funcionales adicionales, los cuales podrían orientar futuras estrategias diagnósticas o terapéuticas.
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