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\begin{document}

\title{Patients with monogenic immune dysregulation show improvement in
childhood interstitial lung disease following targeted therapy -- a case
series and single center approach}



\author[1]{Holly Wobma}%
\author[2]{Ryan Perkins}%
\author[3]{Lisa Bartnikas}%
\author[3]{Fatma Dedeoglu}%
\author[3]{Janet Chou}%
\author[4]{Ruth Ann Vleugels}%
\author[3]{Mindy Lo}%
\author[3]{Erin Janssen}%
\author[3]{Lauren Henderson}%
\author[5]{Jennifer Whangbo}%
\author[6]{Sara Vargas}%
\author[2]{Martha Fishman}%
\author[2]{Katie Krone}%
\author[2]{Alicia Casey}%
\affil[1]{Boston Children's Hospital}%
\affil[2]{Boston Children's Hospital Division of Pulmonary and Respiratory Diseases}%
\affil[3]{Boston Children's Hospital Division of Immunology}%
\affil[4]{Brigham and Women's Hospital Department of Dermatology}%
\affil[5]{Dana-Farber/Boston Children's Cancer and Blood Disorders Center}%
\affil[6]{Boston Children's Hospital Department of Pathology}%


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  \date{June 17, 2024}


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\begin{abstract}
In recent years, a number of monogenic disorders have been described
that are characterized by immune dysregulation. A subset of these
`primary immune regulatory disorders' can cause severe interstitial lung
disease, often recognized in late childhood or adolescence. Patients
presenting to pulmonary clinic may have long and complex medical
histories but lack a unifying genetic diagnosis. It is crucial for
pulmonologists to recognize features suggestive of multisystem immune
dysregulation and to initiate genetic workup, since targeted therapies
based on underlying genetics may halt or even reverese pulmonary disease
progression. Through such an approach, our center has been able to
diagnose and treat a cohort of patients with interstitial lung disease
from gene defects that affect immune regulation. Here we present
representative cases related to pathogenic mutations in three distinct
pathways and summarize disease manifestations and treatment approaches.
We conclude with a discussion of our perspective on the outstanding
challenges for diagnosing and managing these complex life-threatening
and chronic disorders.%
\end{abstract}%



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