Chronic Inflammatory Bowel Disease as Key Manifestation of Atypical ARTEMIS Deficiency
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We describe a girl presenting at age 6 years with a history of chronic ulcerating intestinal inflammation since 9 months of age. She exhibited a severe, steroid-dependent clinical course of intestinal inflammation over several years in the absence of serious infections.
Results and Discussion
Immunodeficiency was first considered at 6 years of age due to chronic lymphopenia. Immunophenotyping revealed low B and T cell counts with few naïve T cells, a skewed TCR repertoire, and TCR γ/δ T cell predominance, suggesting a defect of lymphocyte development. Genetic and functional analyses identified a hypomorphic mutation in the DCLRE1C (ARTEMIS) gene compromising V(D)J recombination efficiency, but allowing residual T and B cell development. Hematopoetic stem cell transplantation reconstituted the lymphocyte compartment and cured the inflammatory bowel disease.
This report illustrates that a genetic disorder of lymphocyte development can present with chronic inflammatory bowel disease as the dominant phenotype in the absence of severe infection susceptibility.
KeywordsInflammatory bowel disease lymphopenia primary immunodeficiency Artemis
anhidrotic ectodermal dysplasia with immunodeficiency
hematopoietic stem cell transplantation
inflammatory bowel disease
immunodysregulation, polyendocrinopathy, enteropathy, X-linked
T cell receptor
This work was supported by the Bundesministerium für Bildung und Forschung (BMBF 01 EO 0803). We acknowledge the excellent technical assistance of S. Braun, I. Janz, and E. M. Rump.
Conflicts of Interest
No conflicts of interest exist for any author.
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