Fabian Hauck1, Sibylle Koletzko2, Christoph Walz3, Horst von Bernuth4, Anne Klenk5, Irene Schmid5, Bernd H Belohradsky5, Christoph Klein5, Philip Bufler2, Michael H Albert5. 1. Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany Immunological Diagnostics Laboratory, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany fabian.hauck@med.uni-muenchen.de. 2. Pediatric Gastroenterology/Hepatology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany. 3. Institute of Pathology, Ludwig-Maximilians University of Munich, Munich, Germany. 4. Pediatric Pneumology and Immunology, Charité University Medicine, Berlin, Germany Labor Berlin, Immunology, Charité and Vivantes GmbH, Berlin, Germany. 5. Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
Abstract
BACKGROUND AND AIMS: X-linked chronic granulomatous disease [X-CGD] due to hemizygous mutations in CYBB is characterised by invasive bacterial and fungal infections and granulomatous inflammation. Inflammatory bowel disease [IBD] is an additional or isolated manifestation. Allogeneic haematopoietic stem cell transplantation [alloHSCT] is the standard curative treatment. X-CGD carriers are usually healthy but those with non-random X-chromosome inactivation [XCI] may develop infectious or autoinflammatory manifestations. METHODS AND RESULTS: We report on two female patients with severe treatment-refractory Crohn-like IBD manifesting at age 23 and 8 years, respectively. NADPH-oxidase activity testing and molecular genetics proved X-CGD carrier status with non-random XCI. As in CGD, histopathology from colonic biopsies disclosed pigment-laden macrophages and reduced CD68(+) macrophages. Following submyelo-ablative conditioning, the younger patient was treated with alloHSCT at age 20 years. She came into remission within 3 months after transplantation and shows complete mucosal healing after 16 months off all medications. CONCLUSIONS: We suggest that children and young adults with refractory IBD should mandatorily be tested for CGD. AlloHSCT should be considered as curative therapy in severely diseased female carriers of X-CGD with non-random XCI.
BACKGROUND AND AIMS: X-linked chronic granulomatous disease [X-CGD] due to hemizygous mutations in CYBB is characterised by invasive bacterial and fungal infections and granulomatous inflammation. Inflammatory bowel disease [IBD] is an additional or isolated manifestation. Allogeneic haematopoietic stem cell transplantation [alloHSCT] is the standard curative treatment. X-CGD carriers are usually healthy but those with non-random X-chromosome inactivation [XCI] may develop infectious or autoinflammatory manifestations. METHODS AND RESULTS: We report on two female patients with severe treatment-refractory Crohn-like IBD manifesting at age 23 and 8 years, respectively. NADPH-oxidase activity testing and molecular genetics proved X-CGD carrier status with non-random XCI. As in CGD, histopathology from colonic biopsies disclosed pigment-laden macrophages and reduced CD68(+) macrophages. Following submyelo-ablative conditioning, the younger patient was treated with alloHSCT at age 20 years. She came into remission within 3 months after transplantation and shows complete mucosal healing after 16 months off all medications. CONCLUSIONS: We suggest that children and young adults with refractory IBD should mandatorily be tested for CGD. AlloHSCT should be considered as curative therapy in severely diseased female carriers of X-CGD with non-random XCI.
Authors: Brenna LaBere; Maria J Gutierrez; Hannah Wright; Elizabeth Garabedian; Hans D Ochs; Ramsay L Fuleihan; Elizabeth Secord; Rebecca Marsh; Kathleen E Sullivan; Charlotte Cunningham-Rundles; Luigi D Notarangelo; Karin Chen Journal: J Allergy Clin Immunol Pract Date: 2022-01-14
Authors: Rebecca A Marsh; Jennifer W Leiding; Brent R Logan; Linda M Griffith; Danielle E Arnold; Elie Haddad; E Liana Falcone; Ziyan Yin; Kadam Patel; Erin Arbuckle; Jack J Bleesing; Kathleen E Sullivan; Jennifer Heimall; Lauri M Burroughs; Suzanne Skoda-Smith; Shanmuganathan Chandrakasan; Lolie C Yu; Benjamin R Oshrine; Geoffrey D E Cuvelier; Monica S Thakar; Karin Chen; Pierre Teira; Shalini Shenoy; Rachel Phelan; Lisa R Forbes; Deepak Chellapandian; Blachy J Dávila Saldaña; Ami J Shah; Katja G Weinacht; Avni Joshi; Farid Boulad; Troy C Quigg; Christopher C Dvorak; Debi Grossman; Troy Torgerson; Pamela Graham; Vinod Prasad; Alan Knutsen; Hey Chong; Holly Miller; M Teresa de la Morena; Kenneth DeSantes; Morton J Cowan; Luigi D Notarangelo; Donald B Kohn; Elizabeth Stenger; Sung-Yun Pai; John M Routes; Jennifer M Puck; Neena Kapoor; Michael A Pulsipher; Harry L Malech; Suhag Parikh; Elizabeth M Kang Journal: J Clin Immunol Date: 2019-08-02 Impact factor: 8.317
Authors: Joyce E Yu; Antoine E Azar; Hey J Chong; Artemio M Jongco; Benjamin T Prince Journal: J Pediatric Infect Dis Soc Date: 2018-05-09 Impact factor: 3.164