Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency
<h3>Purpose</h3><p dir="ltr">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. Ho...
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2024
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| _version_ | 1864513509321080832 |
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| author | Jérémie Rosain (5900399) |
| author2 | Ayca Kiykim (13851559) Alexandre Michev (19342507) Yasemin Kendir-Demirkol (19342510) Darawan Rinchai (742366) Jessica N. Peel (19342513) Hailun Li (14896062) Suheyla Ocak (11158408) Pinar Gokmirza Ozdemir (19342516) Tom Le Voyer (18551572) Quentin Philippot (558140) Taushif Khan (691254) Anna-Lena Neehus (9320912) Mélanie Migaud (5913107) Camille Soudée (19342519) Stéphanie Boisson-Dupuis (64693) Nico Marr (349853) Alessandro Borghesi (1871344) Jean-Laurent Casanova (64712) Jacinta Bustamante (64702) |
| author2_role | author author author author author author author author author author author author author author author author author author author |
| author_facet | Jérémie Rosain (5900399) Ayca Kiykim (13851559) Alexandre Michev (19342507) Yasemin Kendir-Demirkol (19342510) Darawan Rinchai (742366) Jessica N. Peel (19342513) Hailun Li (14896062) Suheyla Ocak (11158408) Pinar Gokmirza Ozdemir (19342516) Tom Le Voyer (18551572) Quentin Philippot (558140) Taushif Khan (691254) Anna-Lena Neehus (9320912) Mélanie Migaud (5913107) Camille Soudée (19342519) Stéphanie Boisson-Dupuis (64693) Nico Marr (349853) Alessandro Borghesi (1871344) Jean-Laurent Casanova (64712) Jacinta Bustamante (64702) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jérémie Rosain (5900399) Ayca Kiykim (13851559) Alexandre Michev (19342507) Yasemin Kendir-Demirkol (19342510) Darawan Rinchai (742366) Jessica N. Peel (19342513) Hailun Li (14896062) Suheyla Ocak (11158408) Pinar Gokmirza Ozdemir (19342516) Tom Le Voyer (18551572) Quentin Philippot (558140) Taushif Khan (691254) Anna-Lena Neehus (9320912) Mélanie Migaud (5913107) Camille Soudée (19342519) Stéphanie Boisson-Dupuis (64693) Nico Marr (349853) Alessandro Borghesi (1871344) Jean-Laurent Casanova (64712) Jacinta Bustamante (64702) |
| dc.date.none.fl_str_mv | 2024-02-16T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s10875-024-01661-5 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Recombinant_IFN-_1b_Treatment_in_a_Patient_with_Inherited_IFN-_Deficiency/26508271 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Immunology Inborn error of immunity Interferon-gamma Mycobacterium BCG |
| dc.title.none.fl_str_mv | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Purpose</h3><p dir="ltr">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).</p><h3>Methods</h3><p dir="ltr">We characterized a new patient with MSMD by genetic, immunological, and clinical means. Therapeutic decisions were taken on the basis of these findings.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusion</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s10875-024-01661-5" target="_blank">https://dx.doi.org/10.1007/s10875-024-01661-5</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_f7dc6d0d0b8c81c7c4a720663263da63 |
| identifier_str_mv | 10.1007/s10875-024-01661-5 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26508271 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ DeficiencyJérémie Rosain (5900399)Ayca Kiykim (13851559)Alexandre Michev (19342507)Yasemin Kendir-Demirkol (19342510)Darawan Rinchai (742366)Jessica N. Peel (19342513)Hailun Li (14896062)Suheyla Ocak (11158408)Pinar Gokmirza Ozdemir (19342516)Tom Le Voyer (18551572)Quentin Philippot (558140)Taushif Khan (691254)Anna-Lena Neehus (9320912)Mélanie Migaud (5913107)Camille Soudée (19342519)Stéphanie Boisson-Dupuis (64693)Nico Marr (349853)Alessandro Borghesi (1871344)Jean-Laurent Casanova (64712)Jacinta Bustamante (64702)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesImmunologyInborn error of immunityInterferon-gammaMycobacteriumBCG<h3>Purpose</h3><p dir="ltr">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).</p><h3>Methods</h3><p dir="ltr">We characterized a new patient with MSMD by genetic, immunological, and clinical means. Therapeutic decisions were taken on the basis of these findings.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusion</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s10875-024-01661-5" target="_blank">https://dx.doi.org/10.1007/s10875-024-01661-5</a></p>2024-02-16T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s10875-024-01661-5https://figshare.com/articles/journal_contribution/Recombinant_IFN-_1b_Treatment_in_a_Patient_with_Inherited_IFN-_Deficiency/26508271CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/265082712024-02-16T09:00:00Z |
| spellingShingle | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency Jérémie Rosain (5900399) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Immunology Inborn error of immunity Interferon-gamma Mycobacterium BCG |
| status_str | publishedVersion |
| title | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency |
| title_full | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency |
| title_fullStr | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency |
| title_full_unstemmed | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency |
| title_short | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency |
| title_sort | Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Immunology Inborn error of immunity Interferon-gamma Mycobacterium BCG |