Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα)
Wayne Bainter, Vassilios Lougaris, Jacqueline G. Wallace, Yousef R. Badran, Rodrigo Hoyos‐Bachiloglu, Zachary T. Peters, Hazel Wilkie, Mrinmoy Das, Erin Janssen, Abdallah Beano, Khaoula Ben Farhat, Christy Kam, Luisa Bercich, Paolo Incardona, Vincenzo Villanacci, Maria Pia Bondioni, Antonella Meini, Manuela Baronio, Phammela Abarzua, Silvia Parolini, Giovanna Tabellini, Stefano Maio, Birgitta Schmidt, Jeffrey D. Goldsmith, George M. Murphy, Georg A. Holländer, Alessandro Plebani, Janet Chou, Raif S. Geha
Abstract
infection. In addition, these mice demonstrate a severe reduction in medullary thymic epithelial cells, impaired thymocyte negative selection, a restricted TCRVβ repertoire, a selective expansion of potentially autoreactive T cell clones, a decreased frequency of regulatory T cells, and infiltration of liver, pancreas, and lung by activated T cells coinciding with organ damage. Hence, this study identifies IKKα deficiency as a previously undescribed cause of primary immunodeficiency with associated autoimmunity.