Characteristics of polyclonal anti-interferon-gamma autoantibodies and novel diagnostic strategies: A prospective cohort study of new biomarkers

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity Pub Date : 2025-05-15 DOI:10.1016/j.jtauto.2025.100292

Xidong Wang , Feng Ye , Hongling Liu , Shaoqiang Li , Jinglu Yang , Xue Yu , Yilei Hui , Yongming Li , Yangqing Zhan , Yan Wang , Jing Liu , Zhengtu Li

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Abstract

Background

Anti-γ interferon autoantibody (AIGA) syndrome is a widespread and grossly underestimated immunodeficiency disorder characterized by high mortality rates and a lack of standardized diagnostic methods. A highly accurate AIGA biomarker that meets the requirements of absolute quantification is urgently needed to enable the early diagnosis and treatment monitoring of the disease. In our study, we aimed to identify the primary components of AIGAs, determine their function, and develop a novel diagnostic method.

Methods

Immune repertoire sequencing and a retrospective antibody subtype index analysis were performed for typical patients. Affinity chromatography was used to isolate and purify IgGs from AIGAs in the plasma of AIGA(+) patients. The clinical application value of chromatography for testing AIGAs was evaluated in a prospective clinical cohort.

Results

A total of 114 eligible subjects were enrolled. Immune repertoire sequencing revealed that 74 % of the AIGA(+) patients had IgG clone types, with the somatic hypermutation (SHM) analysis being the most informative. We isolated AIGAs from the blood and interpreted their affinity and major components completely. Based on the results of this prospective cohort study, AIGAs, an absolute quantitative biomarker, were significantly better than the ELISA method (Delong test, P = 0.0018).

Conclusions

Patients with AIGA syndrome have abnormally elevated IgG levels, with IgG3 subtypes dominating. The disorder is characterized by the rapid acquisition of polyclonal AIGAs. The obtained AIGAs had a good neutralization capacity and potential as absolute quantitative biomarkers.

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多克隆抗干扰素γ自身抗体的特征和新的诊断策略：一项新的生物标志物的前瞻性队列研究

抗γ干扰素自身抗体（AIGA）综合征是一种广泛存在且被严重低估的免疫缺陷疾病，其特点是高死亡率和缺乏标准化的诊断方法。迫切需要一种高精度、满足绝对定量要求的AIGA生物标志物，实现疾病的早期诊断和治疗监测。在我们的研究中，我们旨在鉴定aiga的主要成分，确定其功能，并开发一种新的诊断方法。方法对典型患者进行免疫库测序和回顾性抗体亚型指数分析。采用亲和层析法分离纯化AIGA（+）患者血浆中的IgGs。在前瞻性临床队列中评估色谱法检测aiga的临床应用价值。结果共纳入114名符合条件的受试者。免疫库测序显示，74%的AIGA（+）患者具有IgG克隆类型，其中体细胞超突变（SHM）分析是最具信息量的。我们从血液中分离出AIGAs，并完全解释了它们的亲和力和主要成分。本前瞻性队列研究结果显示，绝对定量生物标志物AIGAs明显优于ELISA法（Delong检验，P = 0.0018）。结论AIGA综合征患者IgG水平异常升高，且以IgG3亚型为主。该疾病的特点是快速获得多克隆AIGAs。获得的AIGAs具有良好的中和能力，具有作为绝对定量生物标志物的潜力。

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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