Scholarlink

Background <p>Gout risk assessment is currently reactive, relying on hyperuricaemia. However, a significant clinical gap exists for individuals who develop gout despite maintaining “normal” serum urate levels. We aimed to identify a plasma proteomic signature that defines a susceptibility state for gout years before clinical onset, specifically within individuals who are normouricaemic at baseline.</p> Methods <p>We analyzed large-scale plasma proteomic data (2,920 proteins) from 33,147 normouricaemic individuals (baseline serum urate &lt; 360 μmol/L) in the UK Biobank. To ensure findings were not artifacts of specific algorithms, we employed a “robustness-first” machine-learning framework encompassing 756 model configurations. Longitudinal protein trajectories were traced up to 15 years prior to diagnosis. Incident osteoarthritis was used as a negative control to evaluate specificity.</p> Results <p>A 10-protein signature (including VSIG4, UBQLN3, and MB) predicted incident gout with high discrimination (ROC-AUC = 0.892). This signature identified a high-risk subgroup with a 4.46-fold increased hazard, independent of baseline serum urate and conventional risk factors. Notably, protein trajectories diverged between future cases and controls 10–15 years before clinical diagnosis, even while serum urate remained within the normal range. The signature showed minimal discrimination for osteoarthritis (AUC ≈ 0.60).</p> Conclusions <p>In 33,147 normouricaemic individuals, plasma proteomics identifies a stable preclinical susceptibility state for gout that exists beyond the traditional serum urate paradigm. This 10-protein signature enables early risk stratification and offers a significant window for precision prevention a decade before clinical onset.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Identification of a 10-protein plasma signature for preclinical gout risk beyond serum urate: a robustness-first proteomic study in 33,147 normouricaemic individuals

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月24日

查看全文
  • Yue Yuan,
  • Huan Zhang,
  • Kun Zhang,
  • Mingzhu Wang,
  • Hao Yan,
  • Junyang Zhang,
  • Chengping Wen,
  • Zheshan Guo,
  • Lin Huang,
  • Zhaoxiang Wang

摘要

Background

Gout risk assessment is currently reactive, relying on hyperuricaemia. However, a significant clinical gap exists for individuals who develop gout despite maintaining “normal” serum urate levels. We aimed to identify a plasma proteomic signature that defines a susceptibility state for gout years before clinical onset, specifically within individuals who are normouricaemic at baseline.

Methods

We analyzed large-scale plasma proteomic data (2,920 proteins) from 33,147 normouricaemic individuals (baseline serum urate < 360 μmol/L) in the UK Biobank. To ensure findings were not artifacts of specific algorithms, we employed a “robustness-first” machine-learning framework encompassing 756 model configurations. Longitudinal protein trajectories were traced up to 15 years prior to diagnosis. Incident osteoarthritis was used as a negative control to evaluate specificity.

Results

A 10-protein signature (including VSIG4, UBQLN3, and MB) predicted incident gout with high discrimination (ROC-AUC = 0.892). This signature identified a high-risk subgroup with a 4.46-fold increased hazard, independent of baseline serum urate and conventional risk factors. Notably, protein trajectories diverged between future cases and controls 10–15 years before clinical diagnosis, even while serum urate remained within the normal range. The signature showed minimal discrimination for osteoarthritis (AUC ≈ 0.60).

Conclusions

In 33,147 normouricaemic individuals, plasma proteomics identifies a stable preclinical susceptibility state for gout that exists beyond the traditional serum urate paradigm. This 10-protein signature enables early risk stratification and offers a significant window for precision prevention a decade before clinical onset.