title: Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS).
abstract: Autoimmune lymphoproliferative syndrome (ALPS), a disorder characterized by immune dysregulation due to disrupted lymphocyte homeostasis, is mainly resulted from the mutations in FAS-mediated apoptotic pathway. In addition, other mutations of the genes such as Fas-ligand (FASLG), Caspase 10 (CASP10) and Caspase 8 (CASP8), NRAS and KRAS have also been observed in a small number of patients with ALPS or ALPS-related disorders. However, approximately 20-30% of patients with ALPS have unidentified defect. Its clinical manifestations observed in multiple family members include unexplained lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias such as thrombocytopenia, neutropenia, and anemia due to excessive production of antibodies by lymphocytes, elevated number of double-negative T (DNT) cells, and increased risk of lymphoma. As a very rare disease, ALPS was first characterized in the early 1990s. More than 300 families with hereditary ALPS have been reported till now; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years. ALPS has historically considered as a primary immune defect presenting in early childhood, however, recent studies have shown that it may be more common than previous thought because adult onset presentation is increasingly becoming recognized and more adult ALPS patients are diagnosed. The new genetic and biological insights have improved the understanding of ALPS and a number of targeted therapeutic strategies such as mycophenolate mofetil, sirolimus, and pentostatin have been successfully applied in ALPS patients with promising treatment efficacy. This article comprehensively reviews the clinical and laboratory manifestations, new research advances in the molecular pathogenesis, diagnosis and treatments of this disorder.
authors: Department of Hematology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China.
authors: Pu
authors: P
authors: Li
authors: State Drug Clinical Trial Agency, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
authors: Ping
authors: P
authors: Huang
authors: Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
authors: Ye
authors: Y
authors: Yang
authors: Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.|State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors: Mu
authors: M
authors: Hao
authors: Department of Pharmacy, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China.
authors: Hongwei
authors: H
authors: Peng
authors: Department of Hematology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China. yx021021@sina.com.
authors: Fei
authors: F
authors: Li
mesh_terms: D000818:Animals; D056735:Autoimmune Lymphoproliferative Syndrome / Q000175:diagnosis* / Q000209:etiology* / Q000378:metabolism / Q000628:therapy*; D015415:Biomarkers; D003131:Combined Modality Therapy; D003937:Diagnosis, Differential; D006801:Humans; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: Autoimmune lymphoproliferative syndrome; Cytopenia; Double-negative T cells; FAS; Gene mutation; Treatment