Abstract
The immune regulator gene AIRE plays an essential role in the establishment of immune tolerance and the prevention of autoimmunity. This transcription factor plays a critical role in promoting self-tolerance in the thymus by regulating the expression of a large number of self-antigens that share the common feature of being tissue-restricted in their expression pattern in the periphery. Dysfunction of AIRE in humans causes a rare disease, autoimmune polyglandular syndrome type 1 (APS1), characterized by an autoimmune response against peripheral tissues, particularly endocrine tissues. Although a few dominant mutations have been described, the inactivation of AIRE is usually caused by recessive mutations. Recent data suggests that alterations in AIRE function contribute not only to APS1 but also to more common forms of autoimmune disease. Here, we present a previously unreported missense mutation (NM_000383.2:c.260 T > C) in exon 2 of the AIRE gene, predicted to cause the substitution (p.(Leu87Pro)) in the CARD domain of the AIRE protein. When inherited in conjunction with another dysfunctional AIRE allele, this mutation was associated with immune dysregulation in a pediatric patient. The presence of hypergammaglobulinemia, malabsorption syndrome, ectodermal dysplasia, mucocutaneous candidiasis, vitiligo, and hypothyroidism as well as the presence of multiple autoantibodies allowed us to confirm an APS1 diagnosis.
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Susana Vitozzi and Eduardo Jorge Fernández are employed by Laboratorios LACE. Partial financial support was provided by Laboratorios LACE, which funded the wet-lab experiments.
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All participants signed consent and informed assent (the 5-year-old proposita and parents) which are in accordance with the ethical standards of the Helsinki declaration of 1964 and its subsequent modifications. This study was approved by the ethical committee of “Reina Fabiola” University Hospital, Córdoba, Argentina.
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Vitozzi, S., Correa, S.G., Lozano, A. et al. A novel missense mutation in the AIRE gene underlying autoimmune polyglandular syndrome type 1. Immunogenetics 76, 69–74 (2024). https://doi.org/10.1007/s00251-023-01324-6
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DOI: https://doi.org/10.1007/s00251-023-01324-6