Novel inflammatory markers in intracerebral hemorrhage: Results from Olink proteomics analysis

Inflammation is a crucial factor in intracerebral hemorrhage (ICH) pathophysiology, but specific inflammatory biomarkers in ICH patients remain unclear. This study aimed to identify novel circulating inflammatory biomarkers for improved ICH prediction and diagnosis. We profiled expression levels of 92 cardiovascular disease related proteins in plasma from 26 matched ICH patients and controls using Olink technology. Differentially expressed proteins were validated using ELISA and RT‐qPCR in a second matched cohort. Receiver operating characteristic (ROC) curves evaluated how well the diagnostic tests performed. The study identified 18 inflammatory‐related proteins with significantly different expression levels between ICH patients and controls. These proteins participate in critical biological processes and pathways, such as the regulation of inflammatory mediator secretion, cell death, immune cell proliferation and differentiation, pathogen response, and PI3K‐Akt and JAK–STAT pathways. Notably, we discovered for the first time that Kidney Injury Molecule‐1 (KIM1) is significantly upregulated in the plasma of ICH patients, suggesting its potential as a predictive and diagnostic biomarker for ICH. Validation results from ELISA and RT‐qPCR showed that Interleukin‐6 (IL‐6), Pentraxin 3 (PTX3), KIM1, and Galectin‐9 (Gal‐9) concentrations were markedly increased in the blood plasma and white matter of individuals with ICH. ROC analysis showed that the combined marker of IL‐6, PTX3, KIM1 and Gal‐9 had a high diagnostic efficacy (AUC = 0.941). This study identified a novel biomarker panel (IL‐6, PTX3, KIM1, Gal‐9) for ICH diagnosis. KIM1 upregulation in ICH patients is a novel finding, further investigation is needed into its expression and function in ICH. This study was divided into two phases. In the first discovery phase, 26 pairs of sex‐ and age‐matched case and control samples were collected, and the differentially expressed inflammation‐related factors were screened using Olink protein detection technology. In the second verification phase, another 26 pairs of sex‐ and age‐matched case and control samples were collected, ELISA and RT‐qPCR experiments were performed to verify the positive factors obtained in the first step.