Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency

Patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In contrast to patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1), patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE- expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases. The presence of autoantibodies against other proteins was assessed in patients with inborn errors of the alternative NF-κB using a microarray of around 20,000 human proteins corresponding to a large proportion of the full-length proteome, many of which were in their native conformation.

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#Autoantibodies #COVID-19 #Microarray #Proteinmicroarray