Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding Domains
Adult-onset immunodeficiency (AOID) with anti-interferon-γ (IFN-γ) autoantibodies (autoAbs) is an emerging immunodeficiency syndrome in Asian countries. The presence of neutralizing anti-IFN-γ autoAbs are significantly associated with severe disseminated opportunistic infections. However, the charac...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01905/full |
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| author | Umpa Yasamut Umpa Yasamut Weeraya Thongkum Weeraya Thongkum Weeraya Thongkum Sutpirat Moonmuang Sutpirat Moonmuang Sutpirat Moonmuang Supachai Sakkhachornphop Romanee Chaiwarith Jutarat Praparattanapan Jiraprapa Wipasa Kriangkrai Chawansuntati Khuanchai Supparatpinyo Khuanchai Supparatpinyo Ethan Lai Chatchai Tayapiwatana Chatchai Tayapiwatana |
| author_facet | Umpa Yasamut Umpa Yasamut Weeraya Thongkum Weeraya Thongkum Weeraya Thongkum Sutpirat Moonmuang Sutpirat Moonmuang Sutpirat Moonmuang Supachai Sakkhachornphop Romanee Chaiwarith Jutarat Praparattanapan Jiraprapa Wipasa Kriangkrai Chawansuntati Khuanchai Supparatpinyo Khuanchai Supparatpinyo Ethan Lai Chatchai Tayapiwatana Chatchai Tayapiwatana |
| author_sort | Umpa Yasamut |
| collection | DOAJ |
| description | Adult-onset immunodeficiency (AOID) with anti-interferon-γ (IFN-γ) autoantibodies (autoAbs) is an emerging immunodeficiency syndrome in Asian countries. The presence of neutralizing anti-IFN-γ autoAbs are significantly associated with severe disseminated opportunistic infections. However, the characteristics of the neutralizing antibodies in patients are poorly defined. To better understand the properties of the anti-IFN-γ autoAbs in patients with opportunistic infections, a simplified competitive-binding ELISA was developed. The domains recognized by anti-IFN-γ autoAbs were assessed based on their competition with commercial neutralizing mouse anti-IFN-γ monoclonal antibodies (mAbs). First, the binding affinity and neutralizing capacity of these mAbs (clones B27, B133.5, and MD-1) were characterized. Kinetic analysis and epitope binning using bio-layer interferometry showed the comparable binding affinity of these mAbs to full-length IFN-γ and to the adjacent binding region. These mAbs did not recognize the synthetic 20-mer peptides and inhibited IFN-γ-mediated functions differently. In a competitive-binding ELISA, the anti-IFN-γ autoAbs in AOID serum blocked B27, B133.5, and MD-1 mAb binding. This evidence suggested that the autoAbs that competed with neutralizing mouse anti-IFN-γ mAbs recognized a discontinuous epitope of homodimeric IFN-γ as these mAbs. The patient autoAbs that recognized the B27 epitope exhibited strong neutralizing activity that was determined by the functional analysis. Our results demonstrated the heterogeneity of the autoAbs against IFN-γ in AOID patients and the different patterns among individuals. These data expand upon the fundamental knowledge of neutralizing anti-IFN-γ autoAbs in AOID patients. |
| first_indexed | 2024-12-16T10:05:47Z |
| format | Article |
| id | doaj.art-8dbb8a76dc5d48ab8711e0ef4ead68ef |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T10:05:47Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-8dbb8a76dc5d48ab8711e0ef4ead68ef2022-12-21T22:35:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-08-011010.3389/fimmu.2019.01905467083Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding DomainsUmpa Yasamut0Umpa Yasamut1Weeraya Thongkum2Weeraya Thongkum3Weeraya Thongkum4Sutpirat Moonmuang5Sutpirat Moonmuang6Sutpirat Moonmuang7Supachai Sakkhachornphop8Romanee Chaiwarith9Jutarat Praparattanapan10Jiraprapa Wipasa11Kriangkrai Chawansuntati12Khuanchai Supparatpinyo13Khuanchai Supparatpinyo14Ethan Lai15Chatchai Tayapiwatana16Chatchai Tayapiwatana17Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandFaculty of Associated Medical Sciences, Center of Biomolecular Therapy and Diagnostic, Chiang Mai University, Chiang Mai, ThailandDivision of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandFaculty of Associated Medical Sciences, Center of Biomolecular Therapy and Diagnostic, Chiang Mai University, Chiang Mai, ThailandPh.D. Program in Biomedical Science, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandDivision of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandFaculty of Associated Medical Sciences, Center of Biomolecular Therapy and Diagnostic, Chiang Mai University, Chiang Mai, ThailandPh.D. Program in Biomedical Science, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandFaculty of Medicine, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, ThailandDepartment of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandDepartment of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandFaculty of Medicine, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, ThailandFaculty of Medicine, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, ThailandFaculty of Medicine, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, ThailandDepartment of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandPall Filtration, Singapore, SingaporeDivision of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandFaculty of Associated Medical Sciences, Center of Biomolecular Therapy and Diagnostic, Chiang Mai University, Chiang Mai, ThailandAdult-onset immunodeficiency (AOID) with anti-interferon-γ (IFN-γ) autoantibodies (autoAbs) is an emerging immunodeficiency syndrome in Asian countries. The presence of neutralizing anti-IFN-γ autoAbs are significantly associated with severe disseminated opportunistic infections. However, the characteristics of the neutralizing antibodies in patients are poorly defined. To better understand the properties of the anti-IFN-γ autoAbs in patients with opportunistic infections, a simplified competitive-binding ELISA was developed. The domains recognized by anti-IFN-γ autoAbs were assessed based on their competition with commercial neutralizing mouse anti-IFN-γ monoclonal antibodies (mAbs). First, the binding affinity and neutralizing capacity of these mAbs (clones B27, B133.5, and MD-1) were characterized. Kinetic analysis and epitope binning using bio-layer interferometry showed the comparable binding affinity of these mAbs to full-length IFN-γ and to the adjacent binding region. These mAbs did not recognize the synthetic 20-mer peptides and inhibited IFN-γ-mediated functions differently. In a competitive-binding ELISA, the anti-IFN-γ autoAbs in AOID serum blocked B27, B133.5, and MD-1 mAb binding. This evidence suggested that the autoAbs that competed with neutralizing mouse anti-IFN-γ mAbs recognized a discontinuous epitope of homodimeric IFN-γ as these mAbs. The patient autoAbs that recognized the B27 epitope exhibited strong neutralizing activity that was determined by the functional analysis. Our results demonstrated the heterogeneity of the autoAbs against IFN-γ in AOID patients and the different patterns among individuals. These data expand upon the fundamental knowledge of neutralizing anti-IFN-γ autoAbs in AOID patients.https://www.frontiersin.org/article/10.3389/fimmu.2019.01905/fullinterferon-γanti-interferon-γ autoantibodyneutralizing antibodycompetitive-binding ELISAadult-onset immunodeficiency |
| spellingShingle | Umpa Yasamut Umpa Yasamut Weeraya Thongkum Weeraya Thongkum Weeraya Thongkum Sutpirat Moonmuang Sutpirat Moonmuang Sutpirat Moonmuang Supachai Sakkhachornphop Romanee Chaiwarith Jutarat Praparattanapan Jiraprapa Wipasa Kriangkrai Chawansuntati Khuanchai Supparatpinyo Khuanchai Supparatpinyo Ethan Lai Chatchai Tayapiwatana Chatchai Tayapiwatana Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding Domains Frontiers in Immunology interferon-γ anti-interferon-γ autoantibody neutralizing antibody competitive-binding ELISA adult-onset immunodeficiency |
| title | Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding Domains |
| title_full | Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding Domains |
| title_fullStr | Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding Domains |
| title_full_unstemmed | Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding Domains |
| title_short | Neutralizing Activity of Anti-interferon-γ Autoantibodies in Adult-Onset Immunodeficiency Is Associated With Their Binding Domains |
| title_sort | neutralizing activity of anti interferon γ autoantibodies in adult onset immunodeficiency is associated with their binding domains |
| topic | interferon-γ anti-interferon-γ autoantibody neutralizing antibody competitive-binding ELISA adult-onset immunodeficiency |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01905/full |
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