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Pulmonary Manifestations of Immune Dysregulation in CTLA-4 Haploinsufficiency and LRBA Deficiency
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  • Katie Krone,
  • Abbey Winant,
  • Sara Vargas,
  • Craig Platt,
  • Lisa Bartnikas,
  • Erin Janssen,
  • Craig Lillehei,
  • Edward Lee,
  • Martha Fishman,
  • Alicia Casey
Katie Krone
Boston Children s Hospital
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Abbey Winant
Boston Children's Hospital
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Sara Vargas
Boston Children's Hospital Department of Pathology
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Craig Platt
Boston Children's Hospital Division of Immunology
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Lisa Bartnikas
Boston Children's Hospital Division of Immunology
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Erin Janssen
Boston Children's Hospital Division of Immunology
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Craig Lillehei
Boston Children's Hospital
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Edward Lee
Boston Children's Hospital
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Martha Fishman
Boston Children's Hospital Division of Pulmonary and Respiratory Diseases
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Alicia Casey
Boston Children's Hospital Division of Pulmonary and Respiratory Diseases
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Abstract

Objective: The primary immunodeficiency syndromes of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency and lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency present with multisystem immune dysregulation. The aim of this study was to characterize and compare the pulmonary manifestations of these two diseases. Methods: We retrospectively analyzed the pulmonary clinical, radiologic, and histopathologic characteristics of 6 patients with CTLA-4 haploinsufficiency and 4 patients with LRBA deficiency with pulmonary involvement followed at a large tertiary care center. Results: Chronic respiratory symptoms were more frequent in patients with LRBA deficiency versus CTLA-4 haploinsufficiency (4/4 versus 1/6). Cough was the most common respiratory symptom. Abnormalities in pulmonary exam and pulmonary function testing were more frequent in LRBA deficiency (4/4, 2/4) compared to CTLA-4 haploinsufficiency (1/6, 2/6). Chest CT findings included mediastinal lymphadenopathy (4/4 in LRBA deficiency versus 1/4 in CTLA-4 haploinsufficiency), pulmonary nodules (4/4, 3/4), ground-glass opacification (4/4, 3/4), and bronchiectasis (3/4, 1/4). Lymphocytic inflammation, concentrated bronchovasculocentrically and paraseptally, was observed in all patients who had lung biopsies (N=3 with LRBA deficiency; N=3 with CTLA-4 haploinsufficiency). Granulomas were seen in all patients with CTLA-4 haploinsufficiency and in no patients with LRBA deficiency. Conclusion: Despite phenotypic overlap amongst these diseases, LRBA deficiency demonstrated greater severity of pulmonary disease, indicated by respiratory symptoms, pulmonary exam, and intrathoracic radiologic findings. Lymphocytic inflammation is a key histologic feature of both of these disorders. Pediatric pulmonologists should suspect these disorders in the appropriate clinical, radiological, and pathological context to better diagnose and treat these patients.

Peer review status:ACCEPTED

25 Oct 2020Submitted to Pediatric Pulmonology
26 Oct 2020Submission Checks Completed
26 Oct 2020Assigned to Editor
28 Oct 2020Reviewer(s) Assigned
18 Nov 2020Review(s) Completed, Editorial Evaluation Pending
19 Nov 2020Editorial Decision: Revise Major
13 Feb 20211st Revision Received
13 Feb 2021Submission Checks Completed
13 Feb 2021Assigned to Editor
13 Feb 2021Reviewer(s) Assigned
25 Feb 2021Review(s) Completed, Editorial Evaluation Pending
25 Feb 2021Editorial Decision: Revise Minor
26 Feb 20212nd Revision Received
02 Mar 2021Submission Checks Completed
02 Mar 2021Assigned to Editor
02 Mar 2021Reviewer(s) Assigned
03 Mar 2021Review(s) Completed, Editorial Evaluation Pending
03 Mar 2021Editorial Decision: Accept