53 - Primary Immunodeficiency and Other Diseases With Immune Dysregulation

Abstract

Infectious and noninfectious pulmonary manifestations are common and often severe in numerous inborn errors of immunity (IEI). Accurate and timely diagnosis of IEI requires detailed clinical characterization of patients, including their age of symptom onset and infection susceptibilities, as well as any inflammatory, autoimmune, or atopic comorbidities. This chapter provides an overview of the clinical presentations of IEI, emphasizing the expected pulmonary phenomena, characteristic laboratory findings, and current therapeutic approaches for specific IEI. Chronic granulomatous disease (CGD), Mendelian susceptibility to mycobacterial disease (MSMD), Toll-like receptor deficiencies, interferonopathies, and complement deficiencies are highlighted as examples of IEI affecting innate immunity. Severe combined immunodeficiency (SCID), ataxia telangiectasia, hyper-IgE and hyper-IgM syndromes, and B-cell deficiencies are chosen as exemplars of disrupted adaptive immunity, while granulomatous lymphocytic interstitial lung disease (GLILD) occurring in the setting of common variable immunodeficiency (CVID) is highlighted as a unique treatment challenge. The ever-growing list of newly defined IEI has—and will continue to—elucidated novel targets for therapeutic intervention, providing insight into how combining infection prevention techniques with immunomodulation may improve patient outcomes, including lung health.