Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration

Dube, Christabel Thembela; Gilbert, Hamish T. J.; Rabbitte, Niamh; Baird, Pauline; Patel, Sonal; Herrera, Jeremy A.; Baricevic-Jones, Ivona; Unwin, Richard D.; Chan, Danny; Gnanalingham, Kanna; Hoyland, Judith A.; Richardson, Stephen M.

Abstract

Background: Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used to diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do not detect changes in the tissue extracellular matrix (ECM) as degeneration progresses. Improved techniques, such as a combination of tissue and blood biomarkers, are needed to monitor the progression of IVD degeneration for more effective treatment plans. Methods: To identify tissue and blood biomarkers associated with degeneration progression, we histologically graded 35 adult human degenerate IVD tissues and matched plasma from the individuals into two groups: mild degenerate and severe degenerate. Mass spectrometry was utilised to characterise proteomic differences in tissue and plasma between the two groups. Top differentially distributed proteins were further validated using immunohistochemistry and qRT-PCR. Additionally, correlational analyses were conducted to define similarities and differences between tissue and plasma protein changes in individuals with mild and severe IVD degeneration. Results: Our data revealed that the abundance of 31 proteins was significantly increased in severe degenerated IVD tissues compared to mild. Functional analyses showed that more than 40% of these proteins were matrisome-related, indicating differences in ECM protein composition between severe and mild degenerate IVD tissues. We confirmed adipocyte enhancer-binding protein 1 (AEBP1) as one of the most significantly enriched core matrisome genes and proteins as degeneration progressed. Compared to others, AEBP1 protein levels best distinguished between mild and severe degenerated IVD tissues with an area under the curve score of 0.768 (95% CI: 0.60–0.93). However, we found that protein changes from associated plasma exhibited a weak relationship with histological grading and AEBP1 tissue levels. Given that systemic plasma changes are complex, a larger sample cohort may be required to identify patterns in blood relating to IVD degeneration progression. Conclusions: In this study, we have identified AEBP1 as a tissue marker for monitoring the severity of disc degeneration in humans. Further work to link alterations in tissue AEBP1 levels to changes in blood-related proteins will be beneficial for detailed monitoring of IVD degeneration thereby enabling more personalised treatment approaches.

Citation

Dube, C. T., Gilbert, H. T. J., Rabbitte, N., Baird, P., Patel, S., Herrera, J. A., …Richardson, S. M. (2025). Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration. Arthritis Research and Therapy, 27(1), Article 28. https://doi.org/10.1186/s13075-025-03489-9

• Journal Article Type: Article
• Acceptance Date: Jan 26, 2025
• Online Publication Date: Feb 10, 2025
• Publication Date: Feb 10, 2025
• Deposit Date: Feb 12, 2025
• Publicly Available Date: Feb 24, 2025
• Journal: Arthritis Research & Therapy
• Print ISSN: 1478-6354
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 1
• Article Number: 28
• DOI: https://doi.org/10.1186/s13075-025-03489-9
• Keywords: Intervertebral disc, Plasma, Biomarkers, Extracellular matrix, Degeneration, Proteomics, Histological grading
• Public URL: https://keele-repository.worktribe.com/output/1074197
• Publisher URL: https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-025-03489-9
• Additional Information: Received: 18 October 2024; Accepted: 26 January 2025; First Online: 10 February 2025; : ; : All donors provided full written informed consent before tissue collection. This study was reviewed and approved by the National Research Ethics Service Committee North West (REC reference: 17/LO/1408).; : Not applicable.; : RDU is a founder and shareholder of Complement Therapeutics Inc (CTx), which is developing complement-targeted therapies initially in ocular disease. CTx played no role in the design, execution or analysis of this study. The remaining authors declare no competing interests.