PDF(Pubmed)
Abstract：
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.
摘要：
慢性非恶性淋巴细胞增生和自身免疫性血细胞减少是儿童免疫血液病的相关表现。他们的诊断分类具有挑战性，但对治疗很重要.自身免疫-淋巴增生综合征（ALPS）是一种遗传定义的先天免疫错误，结合了这些表现，但只能解释一小部分案例。诊断类别，如“ALPS样”疾病，常见可变免疫缺陷(CVID)，或Evans综合征因此被使用。遗传学的进步和靶向治疗的可用性的增加要求更多的面向治疗的疾病分类。此外，影响FAS信号传导的遗传条件的（重新）分析的最新发现要求对ALPS进行更精确的定义。在这次审查中,我们提出的术语自身免疫-淋巴增殖性免疫缺陷(ALPID)是指这样一种疾病表型,该表型对于有针对性治疗的遗传疾病患者是丰富的.对于没有当前分子诊断的患者，它定义了免疫失调性疾病的亚组以供进一步研究。在ALPID的概念中，我们提议修订ALPS分类，将该术语的使用限制在有明确证据表明FAS信号传导紊乱并导致特定生物学和临床后果的条件下。这种提出的重新定义ALPS和其他淋巴组织增生性疾病的方法为许多面临这些疾病的专家提供了疾病分类和诊断的框架。
