Decreased activation-induced cell death by EBV-transformed B-cells from a patient with autoimmune lymphoproliferative syndrome caused by a novel FASLG mutation

Pediatric Research
Raquel Ruiz-GarcíaL M Allende

Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency characterized by chronic lymphoproliferation, autoimmune manifestations, expansion of double-negative T-cells, and susceptibility to malignancies. Most cases of ALPS are caused by germline or somatic FAS mutations. We report the case of an ALPS patient due to a novel homozygous Fasligand gene mutation (ALPS-FASLG). ALPS biomarkers were measured and FASLG mutation was identified. Functional characterization was carried out based on activation-induced cell death (AICD) and cytotoxicity assays. This report describes the cases of a patient who presented a severe form of ALPS-FASLG, and his brother who had died due to complications related to ALPS. Moreover, in another family, we present the first case of lymphoma in a patient with ALPS-FASLG. Functional studies showed defective Fasligand-mediated apoptosis, cytotoxicity, and AICD in T-cell blasts. Otherwise, expression of the FASLG gene and corresponding protein was normal, but the shedding of the Fasligand was impaired in T-cells. Additionally, analyzing Epstein-Barr virus (EBV)-transformed B-cells, our results indicate impaired AICD in ALPS-FASLG patients. Patients with autosomal recessive inheritance of...Continue Reading

References

Jun 1, 1967·The Journal of Pediatrics·V C Canale, C H Smith
Sep 1, 1996·The Journal of Clinical Investigation·J WuJ D Mountz
Oct 2, 2004·The New England Journal of Medicine·Eliska HolzelovaFrédéric Rieux-Laucat
Feb 22, 2008·Critical Reviews in Oncology/hematology·Dirk BrennerRüdiger Arnold
Mar 17, 2010·The Journal of Allergy and Clinical Immunology·Iusta CaminhaJoão Bosco Oliveira
Dec 25, 2010·The Journal of Clinical Investigation·Aude Magerus-ChatinetFrédéric Rieux-Laucat
Aug 4, 2012·The Journal of Allergy and Clinical Immunology·Aude Magerus-ChatinetFrédéric Rieux-Laucat

❮ Previous
Next ❯

Citations

Nov 11, 2017·F1000Research·Karen Bride, David Teachey
Jan 1, 2021·Frontiers in Public Health·Jessica De LomaKarin Broberg
Dec 29, 2020·Critical Reviews in Clinical Laboratory Sciences·Laura Casamayor-PoloLuis M Allende
Jun 26, 2021·Biomedical Journal·Aude MagerusFrédéric Rieux-Laucat
Aug 20, 2021·Gene·Raja Ishaq Nabi KhanAshok Kumar Tiwari
Sep 11, 2021·Expert Review of Clinical Immunology·Michele P Lambert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Discover the latest research on ALPS here.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis