Division of Pediatric Hematology, Children's Hospital of Philadelphia, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.
Curr Opin Pediatr. 2012 Feb;24(1):1-8. doi: 10.1097/MOP.0b013e32834ea739.
Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of disrupted lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. Clinical manifestations include lymphadenopathy, splenomegaly, and autoimmune cytopenias. A number of new insights have improved the understanding of the genetics and biology of ALPS. These will be discussed in this review.
A number of key observations have been made recently that better define the pathophysiology of ALPS, including the characterization of somatic FAS variant ALPS, the identification of haploinsufficiency as a mechanism of decreased Fas expression, and the description of multiple genetic hits in FAS in some families that may explain the variable penetrance of the disease. In addition, ALPS has been shown to be a more common condition, as patients diagnosed with other disorders, including Evans syndrome and common variable immune deficiency, have been found to have ALPS. Finally, the treatment of the disease has changed as splenectomy and rituximab have been shown to have unexpected ALPS-specific toxicities, and mycophenolate mofetil and sirolimus have been demonstrated to have marked activity against the disease.
On the basis of novel advances, the diagnostic algorithm and recommended treatment for ALPS have changed significantly, improving quality of life for many patients.
自身免疫性淋巴增生综合征（ALPS）是一种淋巴细胞稳态失调的疾病，是由于 Fas 凋亡途径的突变引起的。临床表现包括淋巴结病、脾肿大和自身免疫性血细胞减少症。许多新的见解提高了对 ALPS 的遗传学和生物学的理解。本文将对此进行讨论。
最近有一些关键的观察结果更好地定义了 ALPS 的病理生理学，包括体细胞 Fas 变异型 ALPS 的特征、Fas 表达减少的杂合不足机制的鉴定，以及在一些家族中描述的 Fas 中的多个遗传缺陷，这可能解释了该疾病的可变外显率。此外，已经表明 ALPS 是一种更为常见的疾病，因为诊断为其他疾病（包括 Evans 综合征和常见可变免疫缺陷）的患者被发现患有 ALPS。最后，由于脾切除术和利妥昔单抗已被证明具有意想不到的 ALPS 特异性毒性，而吗替麦考酚酯和西罗莫司已被证明对该疾病具有显著的活性，因此疾病的治疗方法发生了变化。
基于新的进展，ALPS 的诊断算法和推荐的治疗方法发生了重大变化，提高了许多患者的生活质量。
