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01-02-2024 | Chronic Inflammatory Bowel Disease | Original Article

“Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease

Authors: Sam J. Olyha, Shannon K. O’Connor, Marat Kribis, Molly L. Bucklin, Dinesh Babu Uthaya Kumar, Paul M. Tyler, Faiad Alam, Kate M. Jones, Hassan Sheikha, Liza Konnikova, Saquib A. Lakhani, Ruth R. Montgomery, Jason Catanzaro, Hongqiang Du, Daniel V. DiGiacomo, Holly Rothermel, Christopher J. Moran, Karoline Fiedler, Neil Warner, Esther P.A.H. Hoppenreijs, Caspar I. van der Made, Alexander Hoischen, Peter Olbrich, Olaf Neth, Alejandro Rodríguez-Martínez, José Manuel Lucena Soto, Annemarie M.C. van Rossum, Virgil A.S.H. Dalm, Aleixo M. Muise, Carrie L. Lucas

Published in: Journal of Clinical Immunology | Issue 2/2024

Abstract

Defining monogenic drivers of autoinflammatory syndromes elucidates mechanisms of disease in patients with these inborn errors of immunity and can facilitate targeted therapeutic interventions. Here, we describe a cohort of patients with a Behçet’s- and inflammatory bowel disease (IBD)-like disorder termed “deficiency in ELF4, X-linked” (DEX) affecting males with loss-of-function variants in the ELF4 transcription factor gene located on the X chromosome. An international cohort of fourteen DEX patients was assessed to identify unifying clinical manifestations and diagnostic criteria as well as collate findings informing therapeutic responses. DEX patients exhibit a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum. Patients have been predominantly treated with anti-inflammatory agents, with the majority of DEX patients treated with biologics targeting TNFα.

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Title: “Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease
Authors: Sam J. Olyha
Shannon K. O’Connor
Marat Kribis
Molly L. Bucklin
Dinesh Babu Uthaya Kumar
Paul M. Tyler
Faiad Alam
Kate M. Jones
Hassan Sheikha
Liza Konnikova
Saquib A. Lakhani
Ruth R. Montgomery
Jason Catanzaro
Hongqiang Du
Daniel V. DiGiacomo
Holly Rothermel
Christopher J. Moran
Karoline Fiedler
Neil Warner
Esther P.A.H. Hoppenreijs
Caspar I. van der Made
Alexander Hoischen
Peter Olbrich
Olaf Neth
Alejandro Rodríguez-Martínez
José Manuel Lucena Soto
Annemarie M.C. van Rossum
Virgil A.S.H. Dalm
Aleixo M. Muise
Carrie L. Lucas
Publication date: 01-02-2024
Publisher: Springer US
Keyword: Chronic Inflammatory Bowel Disease
Published in: Journal of Clinical Immunology / Issue 2/2024
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-023-01610-8

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