Separating the Wheat From the Chaff in Asthma and Bronchiectasis: The Saga Trajectory of a Patient With Adult-Onset RAG1 Deficiency.

Inborn errors of immunity (IEIs) can hide in plain sight among patients with a lifelong history of allergic disorders, such as asthma. Especially in cases of mild antibody deficiency and immune dysregulation, in the absence of definitive IEI diagnosis, the smoldering disease process may go unnoticed and lead to organ damage (eg, bronchiectasis). 1 Baumann U. Routes J.M. Soler-Palacin P. Jolles S. The lung in primary immunodeficiencies: new concepts in infection and inflammation. Front Immunol. 2018; 9: 1837 Crossref PubMed Scopus (57) Google Scholar ,2 Berger M. Geng B. Cameron D.W. Murphy L.M. Schulman E.S. Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease. Respir Med. 2017; 132: 181-188 Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar As routine evaluation of several hundred genes linked to IEIs becomes increasingly attainable and affordable, specific diagnoses can be promptly elucidated, allowing early initiation of therapies best suited for the underlying disease. The success of this process depends on close collaboration between the community and academic specialists, as demonstrated by this case. Our patient was initially followed for moderate persistent asthma, specific antibody deficiency, lymphopenia, and clinical signs of mild immune dysregulation. This report will review the pathway to diagnosis of partial recombination activating gene 1 (RAG1) deficiency (pRD), which not only warranted immunoglobulin replacement therapy but also opened the door for consideration of hematopoietic cell transplantation (HCT).