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.

免疫调节基因AIRE在建立免疫耐受和预防自身免疫方面发挥着重要作用。该转录因子通过调节大量自身抗原的表达，在促进胸腺自身耐受性方面发挥着关键作用，这些自身抗原的共同特征是其在外周的表达模式受到组织限制。人类 AIRE 功能障碍会导致一种罕见疾病，即 1 型自身免疫性多腺体综合征 (APS1)，其特征是针对外周组织，特别是内分泌组织的自身免疫反应。尽管已经描述了一些显性突变，但 AIRE 失活通常是由隐性突变引起的。最近的数据表明，AIRE 功能的改变不仅会导致 APS1，还会导致更常见的自身免疫性疾病。在这里，我们提出了 AIRE 基因外显子 2 中先前未报道的错义突变 (NM_000383.2:c.260 T > C)，预计会导致 AIRE 蛋白 CARD 结构域中的替换 (p.(Leu87Pro))。当与另一个功能失调的 AIRE 等位基因一起遗传时，这种突变与儿科患者的免疫失调有关。高丙种球蛋白血症、吸收不良综合征、外胚层发育不良、皮肤粘膜念珠菌病、白癜风和甲状腺功能减退症以及多种自身抗体的存在使我们能够确认 APS1 的诊断。