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01-03-2022 | Primary Immunodeficiency | Review Article

ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies

Authors: Filippo Consonni, Eleonora Gambineri, Claudio Favre

Published in: Annals of Hematology | Issue 3/2022

Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder characterized by benign or malignant lymphoproliferation and autoimmunity. Classically, ALPS is due to mutations in FAS and other related genes; however, recent research revealed that other genes could be responsible for similar clinical features. Therefore, ALPS classification and diagnostic criteria have changed over time, and several ALPS-like disorders have been recently identified. Moreover, mutations in FAS often show an incomplete penetrance, and certain genotypes have been associated to a dominant or recessive inheritance pattern. FAS mutations may also be acquired or could become pathogenic when associated to variants in other genes, delineating a possible digenic type of inheritance. Intriguingly, variants in FAS and increased TCR αβ double-negative T cells (DNTs, a hallmark of ALPS) have been identified in multifactorial autoimmune diseases, while FAS itself could play a potential role in carcinogenesis. These findings suggest that alterations of FAS-mediated apoptosis could trespass the universe of inborn errors of immunity and that somatic mutations leading to ALPS could only be the tip of the iceberg of acquired immunodeficiencies.

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Title: ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies
Authors: Filippo Consonni
Eleonora Gambineri
Claudio Favre
Publication date: 01-03-2022
Publisher: Springer Berlin Heidelberg
Keywords: Primary Immunodeficiency
Immunodeficiency
Published in: Annals of Hematology / Issue 3/2022
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-022-04761-7

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