Management of Atopy with Dupilumab and Omalizumab in CADINS Disease

Natalie M Diaz-Cabrera; Bradly M Bauman; Mildred A Iro; Gina Dabbah-Krancher; Vered Molho-Pessach; Abraham Zlotogorski; Oded Shamriz; Yael Dinur-Schejter; Tatyana Dubnikov Sharon; Polina Stepensky; Yuval Tal; Eli M Eisenstein; Leonora Pietzsch; Catharina Schuetz; Damien Abreu; Carrie C Coughlin; Megan A Cooper; Joshua D Milner; Anthony Williams; Gil Armoni-Weiss; Andrew L Snow; Jennifer W Leiding

doi:10.1007/s10875-023-01636-y

Management of Atopy with Dupilumab and Omalizumab in CADINS Disease

J Clin Immunol. 2024 Jan 17;44(2):48. doi: 10.1007/s10875-023-01636-y.

Authors

Natalie M Diaz-Cabrera¹, Bradly M Bauman^{2

3}, Mildred A Iro⁴, Gina Dabbah-Krancher^{2

3}, Vered Molho-Pessach^{5

6}, Abraham Zlotogorski⁶, Oded Shamriz^{7

8}, Yael Dinur-Schejter⁹, Tatyana Dubnikov Sharon¹⁰, Polina Stepensky⁹, Yuval Tal¹⁰, Eli M Eisenstein¹¹, Leonora Pietzsch¹², Catharina Schuetz^{12

13}, Damien Abreu¹⁴, Carrie C Coughlin¹⁵, Megan A Cooper¹⁶, Joshua D Milner¹⁷, Anthony Williams⁴, Gil Armoni-Weiss⁶, Andrew L Snow^#¹⁸, Jennifer W Leiding^#^{19

20}

Affiliations

¹ Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
² Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, C-2013, Bethesda, MD, 20814, USA.
³ The Henry M. Jackson Foundation, Bethesda, MD, USA.
⁴ Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
⁵ Pediatric Dermatology Service, Department of Dermatology and Venereology, The Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
⁶ Department of Dermatology and Venereology, The Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
⁷ Clinical Immunology and Allergy Unit, Department of Medicine, The Faculty of Medicine, Hadassah Medical Organization, Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ The Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Institute of Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁹ Department of Bone Marrow Transplantation and Cancer Immunotherapy, The Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel.
¹⁰ Clinical Immunology and Allergy Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
¹¹ Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.
¹² Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹³ UniversitätsCentrum Für Seltene Erkrankungen, Medizinische Fakultät Carl-Gustav-Carus, Technische Universität Dresden, Dresden, Germany.
¹⁴ Division of Dermatology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹⁵ Division of Dermatology, Departments of Medicine & Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹⁶ Division of Rheumatology/Immunology, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹⁷ Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
¹⁸ Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, C-2013, Bethesda, MD, 20814, USA. [email protected].
¹⁹ Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA. [email protected].
²⁰ Institute for Clinical and Translational Research, Johns Hopkins All Childrens Hospital, 600 Fifth Street South, Suite 3200, St. Petersburg, FL, 33701, USA. [email protected].

^# Contributed equally.

PMID: 38231347
DOI: 10.1007/s10875-023-01636-y

Abstract

The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

Keywords: CADINS; CARD11; atopic dermatitis; dupilumab; eczema; omalizumab; urticaria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Monoclonal, Humanized*
Child
Child, Preschool
Chronic Urticaria*
Dermatitis, Atopic* / drug therapy
Dermatitis, Atopic* / genetics
Humans
NF-kappa B
Omalizumab / therapeutic use

Substances

Omalizumab
dupilumab
NF-kappa B
Antibodies, Monoclonal, Humanized