Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency

Article Article scientifique Rapport de cas Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency eng 2024-02-16 2024-02-16 author Rosain Jérémie 0000-0002-2822-161X Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France. jeremie.rosain@institutimagine.org.,University of Paris Cité, Imagine Institute, Paris, France. jeremie.rosain@institutimagine.org.,Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France. jeremie.rosain@institutimagine.org. author Kiykim Ayca 0000-0001-5821-3963 Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey. author Michev Alexandre 0000-0001-5035-3400 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,Pediatric Clinic, IRCCS Policlinico "San Matteo" Foundation, University of Pavia, Pavia, Italy. author Kendir-Demirkol Yasemin 0000-0001-8016-5224 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.,Department of Pediatric Genetics, Umraniye Education and Research Hospital, Istanbul, Turkey. author Rinchai Darawan 0000-0001-8851-7730 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA. author Peel Jessica N 0000-0002-1894-8882 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA. author Li Hailun 0000-0002-0764-2837 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France. author Ocak Suheyla Pediatric Hematology and Oncology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey. author Ozdemir Pinar Gokmirza Pediatric Allergy and Immunology, School of Medicine, Trakya University, Edirne, Turkey. author Le Voyer Tom 0000-0002-7253-3135 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France.,Clinical Immunology Department, Saint-Louis Hospital, AP-HP, Paris, France. author Philippot Quentin Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France. author Khan Taushif 0000-0002-7917-8965 Department of Immunology, Sidra Medicine, Doha, Qatar. author Neehus Anna-Lena 0000-0002-8573-6820 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France. author Migaud Mélanie 0000-0003-3062-1214 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France. author Soudée Camille Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France. author Boisson-Dupuis Stéphanie 0000-0002-7115-116X Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA. author Marr Nico 0000-0002-1927-7072 Department of Immunology, Sidra Medicine, Doha, Qatar.,College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar. author Borghesi Alessandro 0000-0002-8773-9144 Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 442438 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Casanova Jean-Laurent 0000-0002-7782-4169 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France.,University of Paris Cité, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.,Howard Hughes Medical Institute, New York, NY, USA.,Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France. author Bustamante Jacinta 0000-0002-3439-2482 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, INSERM U1163, Paris, France. jbustamant@rockefeller.edu.,University of Paris Cité, Imagine Institute, Paris, France. jbustamant@rockefeller.edu.,Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France. jbustamant@rockefeller.edu.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA. jbustamant@rockefeller.edu. 62 10.1007/s10875-024-01661-5 38363432 0271-9142 PMC10873451 https://link.springer.com/article/10.1007/s10875-024-01661-5 Purpose: Inborn errors of IFN-γ immunity underlie Mendelian susceptibility to mycobacterial disease (MSMD). Twenty-two genes with products involved in the production of, or response to, IFN-γ and variants of which underlie MSMD have been identified. However, pathogenic variants of IFNG encoding a defective IFN-γ have been described in only two siblings, who both underwent hematopoietic stem cell transplantation (HCST). Methods: We characterized a new patient with MSMD by genetic, immunological, and clinical means. Therapeutic decisions were taken on the basis of these findings. Results: The patient was born to consanguineous Turkish parents and developed bacillus Calmette-Guérin (BCG) disease following vaccination at birth. Whole-exome sequencing revealed a homozygous private IFNG variant (c.224 T > C, p.F75S). Upon overexpression in recipient cells or constitutive expression in the patient's cells, the mutant IFN-γ was produced within the cells but was not correctly folded or secreted. The patient was treated for 6 months with two or three antimycobacterial drugs only and then for 30 months with subcutaneous recombinant IFN-γ1b plus two antimycobacterial drugs. Treatment with IFN-γ1b finally normalized all biological parameters. The patient presented no recurrence of mycobacterial disease or other related infectious diseases. The treatment was well tolerated, without the production of detectable autoantibodies against IFN-γ. Conclusion: We describe a patient with a new form of autosomal recessive IFN-γ deficiency, with intracellular, but not extracellular IFN-γ. IFN-γ1b treatment appears to have been beneficial in this patient, with no recurrence of mycobacterial infection over a period of more than 30 months. This targeted treatment provides an alternative to HCST in patients with complete IFN-γ deficiency or at least an option to better control mycobacterial infection prior to HCST. BCG Inborn error of immunity Interferon-gamma Mycobacterium Infant, Newborn Humans Genetic Predisposition to Disease Mycobacterium Infections / genetics Homozygote Mycobacterium bovis NIAID NIH HHS R01 AI095983 United States NCATS NIH HHS UL1 TR001866 United States Agence Nationale de la Recherche ANR-10-IAHU-01 true Journal of clinical immunology 44 3 92e30fe8-48b7-4eba-b4d1-c3136ca75620 Article (Published version) Public Article_scientifique_from_europePmc.pdf 6136640 application/pdf CC BY-4.0 3d4af24788daac496087dce7816956059b2818e8367a1f44e7c32aa23cc61220 7b8db232-ff51-4873-a00b-4a88628f812f Appendix Public 10875_2024_1661_MOESM1_ESM.docx 283092 application/vnd.openxmlformats-officedocument.wordprocessingml.document 5323df516589d82645887cda21e1ebbac20feae9fa5f38120dfcd4e950daab66 openAccess

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Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency	Journal of clinical immunology	2024	9	13
Strategies for preventing group B streptococcal infections in newborns : a nation-wide survey of Italian policies	The Italian Journal of Pediatrics	2017	11	60

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