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Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS)

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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.

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Acknowledgments

This work was financially supported by the grants of the Science and Technology Project from Education Department of Jiangxi province (GJJ14021) and the Natural Science Foundation of Jiangxi province (20142BAB205072)

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The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Department of Hematology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China

      Pu Li & Fei Li

    2. State Drug Clinical Trial Agency, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China

      Ping Huang

    3. Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

      Ye Yang & Mu Hao

    4. State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China

      Mu Hao

    5. Department of Pharmacy, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China

      Hongwei Peng

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    Correspondence to Fei Li.

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    P.L. designed and wrote the manuscript. P.H. contributed to manuscript revision and final manuscript review. Y.Y., M.H., and H.P. contributed to manuscript revision. F.L. contributed to the design of the review and the approval of the final manuscript.

    Pu Li and Ping Huang contributed equally to this work.

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    Li, P., Huang, P., Yang, Y. et al. Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS). Clinic Rev Allerg Immunol 50, 55–63 (2016). https://doi.org/10.1007/s12016-015-8466-y

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