Inherited defects in the complement system

open13noThe complement system plays an essential role in both innate and adaptive immune responses. Any dysregulation in this system can disturb normal host defense and alter inflammatory response leading to both infections and autoimmune diseases. The complement system can be activated through three different pathways. Inherited complement deficiencies have been described for all complement components and their regulators. Despite being rare diseases, complement deficiencies are often severe, with a frequent onset during childhood. We provide an overview of clinical disorders related to these disorders and describe current diagnostic strategies required for their comprehensive characterization and management.openLeonardi L.; La Torre F.; Soresina A.; Federici S.; Cancrini C.; Castagnoli R.; Cinicola B.L.; Corrente S.; Giardino G.; Lougaris V.; Volpi S.; Marseglia G.L.; Cardinale F.Leonardi, L.; La Torre, F.; Soresina, A.; Federici, S.; Cancrini, C.; Castagnoli, R.; Cinicola, B. L.; Corrente, S.; Giardino, G.; Lougaris, V.; Volpi, S.; Marseglia, G. L.; Cardinale, F

Inborn errors of immunity with atopic phenotypes: A practical guide for allergists

Inborn errors of immunity (IEI) are a heterogeneous group of disorders, mainly resulting from mutations in genes associated with immunoregulation and immune host defense. These disorders are characterized by different combinations of recurrent infections, autoimmunity, inflammatory manifestations, lymphoproliferation, and malignancy. Interestingly, it has been increasingly observed that common allergic symptoms also can represent the expression of an underlying immunodeficiency and/or immune dysregulation. Very high IgE levels, peripheral or organ-specific hypereosinophilia, usually combined with a variety of atopic symptoms, may sometimes be the epiphenomenon of a monogenic disease. Therefore, allergists should be aware that severe and/or therapy-resistant atopic disorders might be the main clinical phenotype of some IEI. This could pave the way to target therapies, leading to better quality of life and improved survival in affected patients