Allergic Bronchopulmonary Aspergillosis in Patients with Dominant Negative IL6ST

Author:

Jennifer Roper, MD1, Sebastian Ochoa, MD2, Anahita
Agharahimi, MSN, CRNP2, Justina Pfister, RN2, Magdalena
Walkiewicz, PhD2, Amanda Urban, DNP, CRNP3, Rajarshi
Ghosh, PhD2, Michail Lionakis, MD, ScD2, Lisa Kohn, MD, PhD4, Kenneth Olivier, MD, MPH2, Alexandra Freeman, MD2

Author address:

1 MedStar Georgetown University Hospital, 2 National Institutes of Health, 3 Clinical Research Directorate, Frederick National Laboratory for Cancer Research, 4 University of California, Los Angeles

Full conference title:

American Academy of Allergy, Asthma and Immunology Annual Meeting 2023

Date: 24 February 2023

Abstract:

RATIONALE: Pathogenic variants in IL6ST cause a Hyper-IgE syndrome (HIES) that presents similarly to STAT3 dominant negative (DN) HIES. Severe structural lung disease with bronchiectasis and pneumatoceles is a major driver of morbidity in this disease. We describe clinical characteristics of four patients with heterozygous IL6ST variants with presentations consistent with allergic bronchopulmonary aspergillosis (ABPA). METHODS: Four patients with immune and genetic evaluation for recurrent lung infections were found to have truncating variants resulting in dominant negative IL6ST. Clinical data including historical, laboratory, and radiographic features were collected and described. RESULTS: All four patients (two female, mean age 29.5 years) presented with recurrent pneumonia, asthma, and elevated IgE (mean 5191 IU/ml). 3/ 4 had history of low impact fractures, low bone density, and dental abnormalities. Computed tomography (CT) imaging demonstrated central bronchiectasis in all cases with pneumatoceles and/or cavities. Exome and genome sequencing showed truncating variants in the proximal cytoplasmic region of IL6ST. All patients were evaluated for ABPA and had elevated specific IgE or a positive skin prick test to Aspergillus fumigatus, positive Aspergillus IgG precipitins, and/or eosinophilia (mean 1562 absolute cells/uL). One also had invasive pulmonary aspergillosis. CONCLUSIONS: We described four patients with pathogenic variants in IL6ST (three novel) and destructive lung disease consistent with ABPA. Whether exaggerated type 2 responses to Aspergillus drives structural lung disease in these patients requires further studies.

Abstract Number: 516

Conference Year: 2023

Link to conference website: https://aaaai.planion.com/Web.User/SearchSessions?ACCOUNT=AAAAI&CONF=AM2023&USERPID=PUBLIC&ssoOverride=OFF&MOPT=Search_Sessions&standalone=YES

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