Autoimmune lymphoproliferative syndrome due to somatic FAS mutation (ALPS-sFAS) combined with a germline caspase-10 (CASP10) variation

Immunobiology
Ana Martínez-FeitoLuis M Allende

Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency caused by impaired Fas/FasL-mediated apoptosis of lymphocytes and is characterized by chronic nonmalignant or benign lymphoproliferation, autoimmune manifestations and expansion of double negative (DN) T-cells (TCRαβ+CD4-CD8-). Most cases of ALPS are associated with germline (ALPS-FAS) or somatic (ALPS-sFAS) heterozygous FAS mutations or a combination of both. Here we report three unrelated patients with ALPS-sFAS. Only one of them showed impaired Fas function in PHA-activated T-cells. In this patient, the genetic analysis of the caspase-10 gene (CASP10) identified a heterozygous germline change in exon 9 (c.1337A>G) causing Y446C substitution in the caspase-10 protein. In addition, this patient had a dysregulated T- and B-cell phenotype; circulating lymphocytes showed expansion of T effector memory CD45RA+ (TEMRA) CD4 T-cells, effector memory CD8 T-cells, CD21(low) B-cells and reduced memory switched B-cells. Additionally, this patient showed altered expression in T-cells of several molecules that change during differentiation from naïve to effector cells (CD27, CD95, CD57 and perforin). Molecular alterations in genes of the Fas pathway are necessary ...Continue Reading

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Citations

Nov 11, 2017·F1000Research·Karen Bride, David Teachey
Jul 17, 2019·British Journal of Haematology·Maurizio MianoFrancesca Fioredda
Dec 20, 2018·Immunological Reviews·Sonia Meynier, Frédéric Rieux-Laucat
Jun 19, 2018·Journal of Clinical Immunology·Frédéric Rieux-LaucatBénédicte Neven
Feb 19, 2020·Human Genetics·Conor Gruber, Dusan Bogunovic
Aug 24, 2019·Cell and Tissue Research·Takashi SuzukiYasuhiro Kon
Mar 18, 2020·Genes & Diseases·Ankita SinghAmit Rawat
Dec 29, 2020·Critical Reviews in Clinical Laboratory Sciences·Laura Casamayor-PoloLuis M Allende
May 28, 2021·The New England Journal of Medicine·Satu Mustjoki, Neal S Young
Jun 26, 2021·Biomedical Journal·Aude MagerusFrédéric Rieux-Laucat
Jul 1, 2021·Nature Reviews. Rheumatology·Yuriy BaglaenkoSoumya Raychaudhuri

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