May 15, 2024
Journal Article

Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis


Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), thus creating an unmet need to identify and develop non-invasive biomarkers for AH. In murine models of ethanol-induced liver injury, complement activation contributes to hepatic inflammation and injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of mined data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteomes of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol use disorder (AUD) and healthy controls (HCs). Notably, serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited excellent discriminatory performance amongst patients with sAH, AUD, and HCs. Furthermore, lower serum mannose-binding lectin associated serine protease 1 and coagulation factor II were associated with and predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of AH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

Published: May 15, 2024


Taiwo M.T., E. Huang, V. Pathak, A. Bellar, N. Welch, J. Dasarathy, and D. Streem, et al. 2024. Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis. JCI Insight 9, no. 9:Art. No. e174127. PNNL-SA-188185. doi:10.1172/jci.insight.174127

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