Change search
ReferencesLink to record
Permanent link

Direct link
Early onset combined immunodeficiency and autoimmunity in patients with loss-of-function mutation in LAT
University of Medical Centre, Germany; University of Freiburg, Germany.
Ruth Rappaport Childrens Hospital, Israel.
University of Medical Centre, Germany; University of Freiburg, Germany; University of Freiburg, Germany; University of Freiburg, Germany.
Rambam Health Care Campus, Israel.
Show others and affiliations
2016 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 213, no 7, 1185-1199 p.Article in journal (Refereed) Published
Abstract [en]

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) kappa B 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.

Place, publisher, year, edition, pages
ROCKEFELLER UNIV PRESS , 2016. Vol. 213, no 7, 1185-1199 p.
National Category
Cell and Molecular Biology
URN: urn:nbn:se:liu:diva-131197DOI: 10.1084/jem.20151110ISI: 000380849800009PubMedID: 27242165OAI: diva2:971894

Funding Agencies|German Federal Ministry of Education and Research [BMBF 01EO1303]; Deutsche Forschungsgemeinschaft [DFG WA 1597/4-1]; Hebrew University; Hadassah Medical Center; Excellence Initiative of the German Research Foundation (Spemann Graduate School) [GSC-4]

Available from: 2016-09-19 Created: 2016-09-12 Last updated: 2016-10-12

Open Access in DiVA

fulltext(2336 kB)3 downloads
File information
File name FULLTEXT01.pdfFile size 2336 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Sigvardsson, Mikael
By organisation
Division of Microbiology and Molecular MedicineFaculty of Medicine and Health Sciences
In the same journal
Journal of Experimental Medicine
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 3 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 16 hits
ReferencesLink to record
Permanent link

Direct link