Proteomics Identifies Complement Protein Signatures in Patients with Alcohol-associated Hepatitis

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2024 Apr 4

PMID 38573776

Authors

Moyinoluwa Taiwo

Emily Huang

Vai Pathak

Annette Bellar

Nicole Welch

Jaividhya Dasarathy

David Streem

Craig J McClain

Mack C Mitchell

Bruce A Barton

Gyongyi Szabo

Srinivasan Dasarathy

Esperance A Schaefer

Jay Luther

Le Z Day

Xinshou Ouyang

Arumugam Suyavaran

Wajahat Z Mehal

Jon M Jacobs

Russell P Goodman

Daniel M Rotroff

Laura E Nagy

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Non-Invasive Biomarkers for Differentiating Alcohol Associated Hepatitis from Acute Decompensation in Patients with ALD.

Ignat M, Stefanescu H J Clin Med. 2024; 13(13).

PMID: 38999313 PMC: 11242687. DOI: 10.3390/jcm13133747.

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