Work

The impact of neutralizing anti-IFN-γ autoantibodies on GBP5 expression and monocyte dysfunction in adult-onset immunodeficiency

Year: 2025

Type: article

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. • High levels of neutralizing anti-IFN-γ autoantibodies (AIGAs) are linked to monocyte dysfunction. • AIGAs inhibit GBP5 expression in monocytes, which is crucial for the destruction of intracellular pathogens. • The persistence of neutralizing AIGAs is found at high levels in patients with active and stable/persistent diseases.

Source: Immunobiology

DOI: 10.1016/j.imbio.2025.153134

Authors: Kanokporn Sornsuwan, On-anong Juntit, Kanyarat Thongheang, Ekkarat Wongsawat, Chatchai Tayapiwatana, Umpa Yasamut

Institutions: Chiang Mai University, Siriraj Hospital, Mahidol University

Language: English

Topic: Immunodeficiency and Autoimmune Disorders

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,840