Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency

Abstract NF-κB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant...

Full description

Saved in:
Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2016-03, Vol.164, p.52-56
Main Authors: Klemann, Christian, Pannicke, Ulrich, Morris-Rosendahl, Deborah J, Vlantis, Katerina, Rizzi, Marta, Uhlig, Holm, Vraetz, Thomas, Speckmann, Carsten, Strahm, Brigitte, Pasparakis, Manolis, Schwarz, Klaus, Ehl, Stephan, Rohr, Jan C
Format: Article
Language:English
Subjects:
Alleles
Allergy and Immunology
Anti-TNF treatment
Behcet Syndrome - diagnosis
Behcet Syndrome - genetics
Behcet Syndrome - immunology
Behçet's disease
Female
Hematopoietic Stem Cell Transplantation
HSCT
Humans
I-kappa B Kinase - deficiency
I-kappa B Kinase - genetics
I-kappa B Kinase - immunology
IBD
IKBKG
Inflammatory Bowel Diseases - immunology
Male
NEMO deficiency
Siblings
Skewed X-inactivation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract NF-κB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behçet's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. After transplantation no more severe infections occurred, indicating that an active wild-type NEMO allele in only 10% of immune cells restores host defense. Yet he developed inflammatory bowel disease (IBD). While gut infiltrating immune cells stained strongly for nuclear p65 indicating restored NEMO function, this was not the case in intestinal epithelial cells — in contrast to cells from conventional IBD patients. These results extend murine observations that epithelial NEMO-deficiency suffices to cause IBD. High anti-TNF doses controlled the intestinal inflammation and symptoms of Behçet's disease.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2016.01.010