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A kindred with mutant IKAROS and autoimmunity

Tijdschriftbijdrage - Tijdschriftartikel

IKAROS (encoded by IKZF1) is an important hematopoietic transcription factor critical for early B cell differentiation, with major defects known to lead to low B cell numbers and hypogammaglobulinemia. More perplexing is the link between IKZF1 variants and autoimmunity, including polymorphisms associated with susceptibility to SLE, and recently, rare variants driving monogenic autoimmunity. We identified a novel p.L188V mutation in IKZF1 in the index patient and her father and found this mutation to lead to loss of DNA binding. Peripheral B cells lacking a full complement of IKAROS function show upregulation of molecules accentuating B cell activation, while CD22, a key negative feedback circuit, is suppressed. The resulting hyperresponsiveness of peripheral B cells, in combination with elevated follicular helper T cell (Tfh) numbers, provides a putative mechanistic explanation for the association of IKZF1 variants with the emergence of autoimmune manifestations in this kindred.
Tijdschrift: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
ISSN: 0091-6749
Issue: 2
Volume: 142
Pagina's: 699 - 702
Jaar van publicatie:2018
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:6
CSS-citation score:1
Auteurs:International
Authors from:Government, Higher Education
Toegankelijkheid:Open