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

Taiwo, Moyinoluwa; Huang, Emily; Pathak, Vai; Bellar, Annette; Welch, Nicole; Dasarathy, Jaividhya; Streem, David; McClain, Craig J.; Mitchell, Mack C.; Barton, Bruce A.; Szabo, Gyongyi; Dasarathy, Srinivasan; Schaefer, Esperance A.; Luther, Jay; Day, Le Z.; Ouyang, Xinshou; Suyavaran, Arumugam; Mehal, Wajahat Z.; Jacobs, Jon M.; Goodman, Russell P.; Rotroff, Daniel M.; Nagy, Laura E.

doi:10.1172/jci.insight.174127

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

Journal Article · 04 April 2024 · JCI Insight

DOI: https://doi.org/10.1172/jci.insight.174127 · OSTI ID:2349417

Taiwo, Moyinoluwa ^[1]; Huang, Emily ^[1]; Pathak, Vai ^[1]; Bellar, Annette ^[1];

^[1]; Dasarathy, Jaividhya ^[2];

^[1]; McClain, Craig J. ^[3];

^[4];

^[5]; Szabo, Gyongyi ^[6];

^[7]; Schaefer, Esperance A. ^[8]; Luther, Jay ^[8]; Day, Le Z. ^[9];

^[10]; Suyavaran, Arumugam ^[10]; Mehal, Wajahat Z. ^[10]; Jacobs, Jon M. ^[9]; Goodman, Russell P. ^[8] more »

Cleveland Clinic, OH (United States)
Metro Health Medical Center, Cleveland, OH (United States)
Univ. of Louisville, KY (United States)
Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
Univ. of Massachusetts, Amherst, MA (United States)
Harvard Medical School, Boston, MA (United States)
Cleveland Clinic, OH (United States); Case Western Reserve Univ., Cleveland, OH (United States)
Massachusetts General Hospital, Boston, MA (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)
Yale Univ., New Haven, CT (United States)

Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of 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 proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2349417

Report Number(s):: PNNL-SA--188185

Journal Information:: JCI Insight, Journal Name: JCI Insight Journal Issue: 9 Vol. 9; ISSN 2379-3708

Publisher:: American Society for Clinical InvestigationCopyright Statement

Country of Publication:: United States

Language:: English

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