Many inborn errors of immunity (IEI) manifest with hallmarks of both immunodeficiency and immune dysregulation due to uncontrolled immune responses and impaired immune homeostasis. A subgroup of these disorders frequently presents with autoimmunity and lymphoproliferation (ALPID phenotype). After the initial description of the genetic basis of autoimmune lymphoproliferative syndrome (ALPS) more than 20 years ago, progress in genetics has helped to identify many more genetic conditions underlying this ALPID phenotype. Among these, the majority is caused by a group of autosomal-dominant conditions including CTLA-4 haploinsufficiency, STAT3 gain-of-function disease, activated PI3 kinase syndrome, and NF-κB1 haploinsufficiency. Even within a defined genetic condition, ALPID patients may present with staggering clinical heterogeneity, which makes diagnosis and management a challenge. In this review, we discuss the pathophysiology, clinical presentation, approaches to diagnosis, and conventional as well as targeted therapy of the most common ALPID conditions.

中文翻译：

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儿童期自身免疫性淋巴增殖性免疫缺陷（ALPID）：免疫稳态破坏和免疫失调

许多先天性免疫错误 (IEI) 表现为由于免疫反应不受控制和免疫稳态受损而导致的免疫缺陷和免疫失调的特征。这些疾病的一个亚组经常表现为自身免疫和淋巴细胞增殖（ALPID 表型）。20 多年前首次描述了自身免疫性淋巴组织增生综合征 (ALPS) 的遗传基础，之后遗传学的进展帮助识别了更多潜在于该 ALPID 表型的遗传条件。其中，大多数是由一组常染色体显性病症引起，包括 CTLA-4 单倍体不足、STAT3 功能获得性疾病、激活 PI3 激酶综合征和 NF-κB1 单倍体不足。即使在明确的遗传条件下，ALPID 患者也可能表现出惊人的临床异质性，这给诊断和治疗带来了挑战。在这篇综述中，我们讨论了最常见 ALPID 病症的病理生理学、临床表现、诊断方法以及常规和靶向治疗。