University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
J Allergy Clin Immunol. 2024 Jan;153(1):67-76. doi: 10.1016/j.jaci.2023.11.004. Epub 2023 Nov 17.
Chronic nonmalignant lymphoproliferation and autoimmune cytopenia are relevant manifestations of immunohematologic diseases of childhood. Their diagnostic classification is challenging but important for therapy. Autoimmune lymphoproliferative syndrome (ALPS) is a genetically defined inborn error of immunity combining these manifestations, but it can explain only a small proportion of cases. Diagnostic categories such as ALPS-like disease, common variable immunodeficiency, or Evans syndrome have therefore been used. Advances in genetics and increasing availablity of targeted therapies call for more therapy-oriented disease classification. Moreover, recent discoveries in the (re)analysis of genetic conditions affecting FAS signaling ask for a more precise definition of ALPS. In this review, we propose the term autoimmune lymphoproliferative immunodeficiencies for a disease phenotype that is enriched for patients with genetic diseases for which targeted therapies are available. For patients without a current molecular diagnosis, this term defines a subgroup of immune dysregulatory disorders for further studies. Within the concept of autoimmune lymphoproliferative immunodeficiencies, we propose a revision of the ALPS classification, restricting use of this term to conditions with clear evidence of perturbation of FAS signaling and resulting specific biologic and clinical consequences. This proposed approach to redefining ALPS and other lymphoproliferative conditions provides a framework for disease classification and diagnosis that is relevant for the many specialists confronted with these diseases.
慢性非恶性淋巴增生症和自身免疫性血细胞减少症是儿童免疫血液疾病的相关表现。其诊断分类具有挑战性，但对治疗很重要。自身免疫性淋巴增生综合征（ALPS）是一种遗传性免疫缺陷病，可同时出现这些表现，但它只能解释一小部分病例。因此，使用了一些诊断类别，如 ALPS 样疾病、常见可变免疫缺陷或 Evans 综合征。遗传学的进步和靶向治疗的可用性增加，要求对疾病进行更具针对性的分类。此外，最近在影响 Fas 信号转导的遗传疾病的（重新）分析中发现，需要更精确地定义 ALPS。在这篇综述中，我们提出了自身免疫性淋巴增生性免疫缺陷的术语，用于一种疾病表型，该表型富含可进行靶向治疗的遗传疾病患者。对于目前没有分子诊断的患者，该术语定义了免疫调节紊乱疾病的一个亚组，以进行进一步研究。在自身免疫性淋巴增生性免疫缺陷的概念中，我们提出了对 ALPS 分类的修订，将该术语的使用限于明确证据表明 Fas 信号转导受到干扰且导致特定生物学和临床后果的情况。这种重新定义 ALPS 和其他淋巴增生性疾病的方法为疾病分类和诊断提供了一个框架，对许多面临这些疾病的专家具有重要意义。
