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

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunobiology Pub Date : 2025-11-01 Epub Date: 2025-10-30 DOI:10.1016/j.imbio.2025.153134

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

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引用次数: 0

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.

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中和抗ifn -γ自身抗体对成人发病免疫缺陷中GBP5表达和单核细胞功能障碍的影响。

抗干扰素γ (IFN-γ)自身抗体（aiga）与成人发病免疫缺陷（AOID）的机会性感染有关。这些自身抗体，特别是识别c端线性表位（P128-143）和B27表位的自身抗体，会阻断单核细胞中IFN-γ的功能，从而导致疾病。在对45例患者的残留血浆的回顾性分析中，我们通过间接ELISA证实了aiga的存在，并评估了它们中和IFN-γ诱导的MHC-II表达的能力。所有样品均表现出中和能力，但具有不同的表位识别能力：10个样品具有同时识别两种表位的aiga， 7个样品具有识别B27表位的aiga， 12个样品具有识别P128-143表位的aiga， 16个样品两者均不具有。抑制水平从36.5%到91.6%不等。含有至少B27表位识别AIGAs的5个代表性样品可以抑制鸟苷酸结合蛋白5 （guanyate binding protein 5, GBP5）的表达，这是杀死病原体的关键。此外，在活动性和稳定性疾病患者中，高水平的中和性AIGAs持续存在。总的来说，这些数据强调了中和AIGA水平、群体特征和AIGA持续存在与单核细胞功能障碍和疾病结局之间的关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.