Inborn errors of immunity with overlap of allergy and autoimmune disease

Inborn errors of immunity (IEI) are increasingly recognized to present clinically not just with infection, but also with symptoms of immune dysregulation, including autoimmunity and severe atopy. IEI with atopy and autoimmunity can be grouped into 3 broad categories: (1) cytoskeletal impairments, (2) cytokine signaling impairments, and (3) T cell receptor signaling impairments. In addition, primary immune regulatory disorders (PIRDs) are a subset of IEI that have been described with increasing frequency over the past 5 years as presenting predominantly with symptoms of immune dysregulation rather than severe or opportunistic infections. These PIRDs can present with overlaps of both atopy, most typically atopic dermatitis, and severe autoimmunity. In the latest International Union of Immunology Societies genotypic categorization of IEIs, PIRDs were the group with the largest expansion of newly identified monogenic etiologies, suggesting that patients with these conditions in our clinic are waiting to be identified, and with the hope that identification of a monogenic cause can drive the effective use of pathway-specific, precision therapy. In this review, we provide an overview of the mechanisms behind T cell development or deficiency that can contribute to the development of atopy and autoimmunity, review selected monogenic forms of PIRDs that present with an overlap of atopy and autoimmunity, and provide an overview of approaches to diagnostic testing for and management of these conditions in the allergy and immunology clinical setting.