The impact of neutralizing anti-IFN-γ autoantibodies on GBP5 expression and monocyte dysfunction in adult-onset immunodeficiency
Issued Date
2025-01-01
Resource Type
ISSN
01712985
eISSN
18783279
Scopus ID
2-s2.0-105024680995
Pubmed ID
41187578
Journal Title
Immunobiology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Immunobiology (2025)
Suggested Citation
Sornsuwan K., Juntit O.a., Thongheang K., Wongsawat E., Tayapiwatana C., Yasamut U. The impact of neutralizing anti-IFN-γ autoantibodies on GBP5 expression and monocyte dysfunction in adult-onset immunodeficiency. Immunobiology (2025). doi:10.1016/j.imbio.2025.153134 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113604
Title
The impact of neutralizing anti-IFN-γ autoantibodies on GBP5 expression and monocyte dysfunction in adult-onset immunodeficiency
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Corresponding Author(s)
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Abstract
Anti-interferon gamma (IFN-γ) autoantibodies (AIGAs) are linked to opportunistic infections in adult-onset immunodeficiency (AOID). These autoantibodies, particularly those recognizing the C-terminal linear epitope (P128–143) and B27 epitope, block IFN-γ functions in monocytes, contributing to disease. In a retrospective analysis of residual plasma from 45 AOID patients, we confirmed the presence of AIGAs by indirect ELISA and evaluated their capacity to neutralize IFN-γ–induced MHC-II expression. All samples showed neutralizing capability, with varying epitope recognition: 10 samples had AIGAs which recognize both epitopes, 7 had B27 epitope-recognizing AIGAs, 12 had P128–143 epitope-recognizing AIGAs, and 16 had neither. Inhibition levels ranged from 36.5 % to 91.6 %. Five representative samples containing at least B27 epitope-recognizing AIGAs could inhibit guanylate binding protein 5 (GBP5) expression, crucial for pathogen killing. Additionally, high levels of neutralizing AIGAs persisted in patients with active and stable diseases. Overall, the data underscore the relationship between neutralizing AIGA levels, population characteristics, and persistence of AIGAs with monocyte dysfunction and disease outcome.