Epigenetics and Immune Disease Group, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain.
Department of Pediatrics, Division of Immunology, Allergy, and Retrovirology, Baylor College of Medicine, Houston, TX, USA; William T. Shearer Texas Children's Hospital Center for Human Immunobiology, Houston, TX, USA.
Trends Immunol. 2023 Nov;44(11):902-916. doi: 10.1016/j.it.2023.09.005. Epub 2023 Oct 7.
Inborn errors of immunity (IEIs) comprise a variety of immune conditions leading to infections, autoimmunity, allergy, and cancer. Some IEIs have no identified mutation(s), while others with identical mutations can display heterogeneous presentations. These observations suggest the involvement of epigenetic mechanisms. Epigenetic alterations can arise from downstream activation of cellular pathways through both extracellular stimulation and genetic-associated changes, impacting epigenetic enzymes or their interactors. Therefore, we posit that epigenetic alterations and genetic defects do not exclude each other as a disease-causing etiology. In this opinion, encompassing both basic and clinical viewpoints, we focus on selected IEIs with mutations in transcription factors that interact with epigenetic enzymes. The intricate interplay between these factors offers insights into genetic and epigenetic mechanisms in IEIs.
先天性免疫缺陷（IEIs）包括多种导致感染、自身免疫、过敏和癌症的免疫疾病。一些 IEIs 没有明确的突变，而其他具有相同突变的患者可能表现出异质性。这些观察结果表明，表观遗传机制的参与。表观遗传改变可以通过细胞途径的下游激活产生，包括细胞外刺激和遗传相关的改变，影响表观遗传酶或其相互作用蛋白。因此，我们假设，表观遗传改变和遗传缺陷并不相互排斥，都是致病病因。在这篇观点文章中，我们同时包含了基础和临床观点，重点关注转录因子基因突变与表观遗传酶相互作用的几种 IEIs。这些因素之间的复杂相互作用为 IEIs 中的遗传和表观遗传机制提供了深入的了解。
