Down syndrome fits an immunophenotype of combined immunodeficiency with immunodysregulation, manifesting with increased susceptibility to infections, autoimmunity, autoinflammatory diseases, and hematologic malignancies. Qualitative and quantitative alterations in innate and adaptive immunity are found in most individuals with Down syndrome. However, there is substantial heterogeneity and no correlation between immunophenotype and clinical presentation. Previously, it was thought that the immunological changes in Down syndrome were caused by precocious aging. We emphasize in this review that the immune system in Down syndrome is intrinsically different from the very beginning. The overexpression of specific genes located on chromosome 21 contributes to immunodeficiency and immunodysregulation, but gene expression differs between genes located on chromosome 21 and depends on tissue and cell type. In addition, trisomy 21 results in gene dysregulation of the whole genome, reflecting the complex nature of this syndrome in comparison to well-known inborn errors of immunity that result from monogenic germline mutations. In this review, we provide an updated overview focusing on inborn errors of adaptive immunity in Down syndrome.

唐氏综合征符合联合免疫缺陷和免疫失调的免疫表型，表现为对感染、自身免疫、自身炎症性疾病和血液系统恶性肿瘤的易感性增加。在大多数唐氏综合症患者中发现先天免疫和适应性免疫的定性和定量改变。然而，免疫表型与临床表现之间存在很大的异质性且没有相关性。以前，人们认为唐氏综合症的免疫学变化是由早熟引起的。我们在这篇综述中强调，唐氏综合症的免疫系统从一开始就有着本质的不同。位于 21 号染色体上的特定基因的过度表达导致免疫缺陷和免疫失调，但基因表达因位于 21 号染色体上的基因而异，并取决于组织和细胞类型。此外，与众所周知的由单基因种系突变引起的先天免疫错误相比，21 三体导致整个基因组的基因失调，反映了这种综合征的复杂性。在这篇综述中，我们提供了一个更新的概述，重点关注唐氏综合症中适应性免疫的先天性错误。