Clinical and Immunological Phenotype of Patients With Primary Immunodeficiency Due to Damaging Mutations in NFKB2
We conclude that heterozygous damaging mutations in NFKB2 represent a distinct PID entity exceeding the usual clinical spectrum of CVID. Impairment of the non-canonical NF-κB pathway affects pivotal mechanisms of central tolerance as well as function and differentiation of numerous lymphocyte-subpopulations. Therefore, damaging NFKB2 mutations cause a more severe form of PID with early-onset and a distinct, multifaceted auto-immunity with primarily T cell mediated autoimmune diseases, such as alopecia, lymphocytic organ infiltration, and possibly ACTH-deficiency.
The authors would like to thank the patients and their families as well as all physicians involved in their care for their active contribution. We thank Katrin Hübscher, Mary Buchta, Pavla Mrovecova, Hanna Haberstroh, and Ruth Dräger as well as the CCI advanced diagnostic unit for excellent technical assistance and Prof. Stephan Ehl for support und helpful discussion.