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ORIGINAL RESEARCH article

Front. Vet. Sci.
Sec. Comparative and Clinical Medicine
Volume 11 - 2024 | doi: 10.3389/fvets.2024.1431738

Quantitative proteomic analysis and replacement therapy identifies Haptoglobin as a therapeutic target in a murine model of SLE-associated diffuse alveolar hemorrhage

Provisionally accepted
Ninghui Yan Ninghui Yan Chenyi Shao Chenyi Shao Yan Zhen Yan Zhen Xueliang Zhang Xueliang Zhang Nana Xia Nana Xia Qiang Guo Qiang Guo *
  • Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

The final, formatted version of the article will be published soon.

    Background: Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome and one of the manifestations of pulmonary involvement in systemic lupus erythematosus (SLE), characterized by hemoptysis, diffuse pulmonary infiltrates, and respiratory failure. However, the treatment options for DAH remain limited, and DAH-related studies are needed to explore more effective therapeutic directions for DAH for better disease management and improved prognosis. Methods: This study utilized the pristane-induced DAH murine model to mimic the pathological process of DAH in patients with SLE. Proteomic analysis was conducted to detect differentially expressed proteins (DEPs) in the plasma of surviving and non-surviving mice, followed by an analysis of biological functions and pathways. The most significant DEP was then confirmed in the plasma of SLE patients with or without DAH, as well as in the DAH murine model with or without fatal outcomes. Finally, the therapeutic value of haptoglobin (Hp) replacement was validated in a DAH murine model through lung histopathology, RT-qPCR, and survival analysis. Results: This study identified a total of 178 DEPs, with 118 up-regulated and 60 down-regulated in the non-survival group. Within a set of notable Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, complement and coagulation cascades emerged as the most prominent pathway associated with the process of DAH. Later, the most significant DEP, haptoglobin (Hp), was confirmed to exhibit a significant decrease in the plasma of individuals with SLE-DAH and in the DAH murine model with poor outcomes by ELISA test. Finally, compared to the control group, the severity of DAH in the Hp treatment group was alleviated significantly, manifested by the decreased levels of pro-inflammatory cytokines (IL-6 and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β), and decreased mortality. Conclusion: A reduction in plasma Hp levels was observed in SLE-DAH, and replacement therapy with Hp could alleviate pulmonary hemorrhage and reduce mortality in DAH mice. This study identified Hp as a potential biomarker for its clinical diagnosis and a direction for treatment.

    Keywords: Diffuse alveolar hemorrhage (DAH), systemic lupus erythematosus (SLE), Proteomics, Haptoglobin (Hp), Differentially expressed proteins

    Received: 23 May 2024; Accepted: 23 Jul 2024.

    Copyright: © 2024 Yan, Shao, Zhen, Zhang, Xia and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qiang Guo, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.