The lung in inborn errors of immunity: From clinical disease patterns to molecular pathogenesis

Maria J. Gutierrez, Division of Pediatric Allergy, Immunology and Rheumatology, Johns Hopkins University, Baltimore, Md. Electronic address: mgutie10@jhmi.edu.
Gustavo Nino, Division of Pediatric Pulmonary and Sleep Medicine, Children's National Hospital, Washington, DC; Department of Pediatrics, George Washington University School of Medicine, Washington, DC.
Di Sun, Division of Pediatric Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pa.
Sonia Restrepo-Gualteros, Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia; Division of Pediatric Pulmonology, Fundacion Hospital La Misericordia, Bogotá, Colombia.
Sarah C. Sadreameli, Division of Pediatric Pulmonology and Sleep Medicine, Johns Hopkins University, Baltimore, Md.
Elizabeth K. Fiorino, Departments of Science Education and Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY.
Eveline Wu, Division of Pediatric Allergy, Immunology and Rheumatology, University of North Carolina, Chapel Hill, NC.
Timothy Vece, Division of Pediatric Pulmonology, University of North Carolina, Chapel Hill, NC.
James S. Hagood, Division of Pediatric Pulmonology, University of North Carolina, Chapel Hill, NC.
Paul J. Maglione, Division of Allergy and Immunology, Boston University, Boston, Mass.
Geoffrey Kurland, Division of Pediatric Pulmonology and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pa.
Anastassios Koumbourlis, Division of Pediatric Pulmonary and Sleep Medicine, Children's National Hospital, Washington, DC; Department of Pediatrics, George Washington University School of Medicine, Washington, DC.
Kathleen E. Sullivan, Division of Pediatric Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Document Type

Journal Article

Publication Date

12-1-2022

Journal

The Journal of allergy and clinical immunology

Volume

150

Issue

6

DOI

10.1016/j.jaci.2022.08.024

Keywords

Inborn errors of immunity; autoimmunity; autoinflammation; bronchiectasis; immune dysregulation; interstitial lung disease; lung infections; primary immunodeficiencies

Abstract

In addition to being a vital organ for gas exchange, the lung is a crucial immune organ continuously exposed to the external environment. Genetic defects that impair immune function, called inborn errors of immunity (IEI), often have lung disease as the initial and/or primary manifestation. Common types of lung disease seen in IEI include infectious complications and a diverse group of diffuse interstitial lung diseases. Although lung damage in IEI has been historically ascribed to recurrent infections, contributions from potentially targetable autoimmune and inflammatory pathways are now increasingly recognized. This article provides a practical guide to identifying the diverse pulmonary disease patterns in IEI based on lung imaging and respiratory manifestations, and integrates this clinical information with molecular mechanisms of disease and diagnostic assessments in IEI. We cover the entire IEI spectrum, including immunodeficiencies and immune dysregulation with monogenic autoimmunity and autoinflammation, as well as recently described IEI with pulmonary manifestations. Although the pulmonary manifestations of IEI are highly relevant for all age groups, special emphasis is placed on the pediatric population, because initial presentations often occur during childhood. We also highlight the pivotal role of genetic testing in the diagnosis of IEI involving the lungs and the critical need to develop multidisciplinary teams for the challenging evaluation of these rare but potentially life-threatening disorders.

Department

Pediatrics

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