Early onset combined immunodeficiency and autoimmunity in patients with loss-of-function mutation in LAT

Abstract: The adapter protein linker for activation of T cells (LAT) is a critical signaling hub connecting T cell antigen receptor triggering to downstream T cell responses. In this study, we describe the first kindred with defective LAT signaling caused by a homozygous mutation in exon 5, leading to a premature stop codon deleting most of the cytoplasmic tail of LAT, including the critical tyrosine residues for signal propagation. The three patients presented from early childhood with combined immunodeficiency and severe autoimmune disease. Unlike in the mouse counterpart, reduced numbers of T cells were present in the patients. Despite the reported nonredundant role of LAT in Ca2+ mobilization, residual T cells were able to induce Ca2+ influx and nuclear factor (NF) κB signaling, whereas extracellular signal-regulated kinase (ERK) signaling was completely abolished. This is the first report of a LAT-related disease in humans, manifesting by a progressive combined immune deficiency with severe autoimmune disease

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Journal of experimental medicine. - 213, 7 (2016) , 1185-1199, ISSN: 1540-9538

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2019
• Urheber: Keller, Bärbel ; Zaidman, Irina ; Yousefi, Omid Sascha ; Hershkovitz, Dov ; Stein, Jerry ; Unger, Susanne ; Schachtrup, Kristina ; Sigvardsson, Mikael ; Kuperman, Amir A. ; Shaag, Avraham ; Schamel, Wolfgang ; Elpeleg, Orly ; Warnatz, Klaus ; Stepensky, Polina
• Beteiligte Personen und Organisationen: Centrum für Chronische Immundefizienz ; Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie ; Arbeitsgruppe Immunologie, Prof. Dr. Wolfgang W. Schamel ; Albert-Ludwigs-Universität Freiburg. CIBSS - Centre for Integrative Biological Signalling Studies

Weitere Informationen

• DOI: 10.1084/jem.20151110
• URN: urn:nbn:de:bsz:25-freidok-1359956
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:47 MEZ