A Kindred With Mutant IKAROS and Autoimmunity

    April 2018 in “ Journal of Allergy and Clinical Immunology ”
    Erika Van Nieuwenhove, Josselyn E. Garcia‐Perez, Christine Helsen, Princess D. Rodriguez, Pauline A. van Schouwenburg, James Dooley, Susan Schlenner, Mirjam van der Burg, Els Verhoeyen, Rik Gijsbers, Seth Frietze, Hilde Schjerven, Isabelle Meyts, Frank Claessens, Stéphanie Humblet‐Baron, Carine Wouters, Adrian Liston
    TLDR A mutation in the IKZF1 gene causes immune system overactivity, linked to autoimmune diseases like lupus.
    The study identified a novel p.L188V mutation in the IKZF1 gene, which encodes the transcription factor IKAROS, in a family with autoimmune manifestations. This mutation resulted in a loss of DNA binding capacity, leading to hyperresponsive peripheral B cells and increased follicular helper T cell numbers. It was associated with decreased expression of CD22, a molecule crucial for negative feedback, contributing to B cell hyperactivation. The findings provided a mechanistic explanation for the link between IKZF1 variants and autoimmunity, particularly systemic lupus erythematosus (SLE), highlighting IKAROS's role in regulating B cell activation and its potential impact on autoimmune diseases.
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