Magg, Thomas; Shcherbina, Anna; Arslan, Duran; Desai, Mukesh M.; Wall, Sarah; Mitsialis, Vanessa; Conca, Raffaele; Unal, Ekrem; Karacabey, Neslihan; Mukhina, Anna; Rodina, Yulia; Taur, Prasad D.; Illig, David; Marquardt, Benjamin; Hollizeck, Sebastian; Jeske, Tim; Gothe, Florian; Schober, Tilmann; Rohlfs, Meino; Koletzko, Sibylle; Lurz, Eberhard; Muise, Aleixo M.; Snapper, Scott B.; Hauck, Fabian; Klein, Christoph; Kotlarz, Daniel (2019): CARMIL2 Deficiency Presenting as Very Early Onset Inflammatory Bowel Disease. In: Inflammatory Bowel Diseases, Vol. 25, No. 11: pp. 1788-1795 |
Abstract
Background: Children with very early onset inflammatory bowel diseases (VEO-IBD) often have a refractory and severe disease course. A significant number of described VEO-IBD-causing monogenic disorders can be attributed to defects in immune-related genes. The diagnosis of the underlying primary immunodeficiency (PID) often has critical implications for the treatment of patients with IBD-like phenotypes. Methods: To identify the molecular etiology in 5 patients from 3 unrelated kindred with IBD-like symptoms, we conducted whole exome sequencing. Immune workup confirmed an underlying PID. Results: Whole exome sequencing revealed 3 novel CARMIL2 loss-of-function mutations in our patients. Immunophenotyping of peripheral blood mononuclear cells showed reduction of regulatory and effector memory T cells and impaired B cell class switching. The T cell proliferation and activation assays confirmed defective responses to CD28 costimulation, consistent with CARMIL2 deficiency. Conclusion: Our study highlights that human CARMIL2 deficiency can manifest with IBD-like symptoms. This example illustrates that early diagnosis of underlying PID is crucial for the treatment and prognosis of children with VEO-IBD.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 1078-0998 |
Language: | English |
ID Code: | 78822 |
Deposited On: | 15. Dec 2021 14:45 |
Last Modified: | 15. Dec 2021 14:45 |
- BASE
- Magg, Thomas
- Shcherbina, Anna
- Arslan, Duran
- Desai, Mukesh M.
- Wall, Sarah
- Mitsialis, Vanessa
- Conca, Raffaele
- Unal, Ekrem
- Karacabey, Neslihan
- Mukhina, Anna
- Rodina, Yulia
- Taur, Prasad D.
- Illig, David
- Marquardt, Benjamin
- Hollizeck, Sebastian
- Jeske, Tim
- Gothe, Florian
- Schober, Tilmann
- Rohlfs, Meino
- Koletzko, Sibylle
- Lurz, Eberhard
- Muise, Aleixo M.
- Snapper, Scott B.
- Hauck, Fabian
- Klein, Christoph
- Kotlarz, Daniel
- Google Scholar
- Magg, Thomas
- Shcherbina, Anna
- Arslan, Duran
- Desai, Mukesh M.
- Wall, Sarah
- Mitsialis, Vanessa
- Conca, Raffaele
- Unal, Ekrem
- Karacabey, Neslihan
- Mukhina, Anna
- Rodina, Yulia
- Taur, Prasad D.
- Illig, David
- Marquardt, Benjamin
- Hollizeck, Sebastian
- Jeske, Tim
- Gothe, Florian
- Schober, Tilmann
- Rohlfs, Meino
- Koletzko, Sibylle
- Lurz, Eberhard
- Muise, Aleixo M.
- Snapper, Scott B.
- Hauck, Fabian
- Klein, Christoph
- Kotlarz, Daniel