Do microenvironmental changes in degenerative disc disease reflect in systemic circulation? A proteomic investigation

Area of Science:

• Immunology
• Proteomics
• Biochemistry

Background:

• The complement system is integral to immune regulation and inflammation, implicated in intervertebral disc degeneration (IDD).
• While local complement activation in degenerated discs is known, systemic complement expression in degenerative disc disease (DDD) plasma is not well understood.

Purpose of the Study:

• To investigate systemic complement protein expression in the plasma of patients with degenerative disc disease (DDD).
• To explore the potential of plasma complement proteins as blood-based biomarkers for DDD.

Main Methods:

• High-throughput mass spectrometry was used to analyze plasma proteomes from 40 DDD patients (Modic change and non-Modic change) and 20 healthy volunteers.
• Proteomic data were analyzed to identify differentially expressed complement proteins and assess correlations with systemic inflammation markers like C-reactive protein (CRP).

Main Results:

• Proteomic analysis identified significant differences in plasma protein profiles between DDD patients and healthy volunteers, with enrichment of complement and coagulation cascades.
• Most complement proteins were upregulated in DDD plasma, with notable exceptions including C1q complex and Complement Factor D (CFD).
• Elevated C-reactive protein (CRP) levels in DDD plasma indicated systemic inflammation, though correlations between plasma and tissue complement levels were weak.

Conclusions:

• Systemic complement alterations in DDD plasma suggest their potential utility as blood-based biomarkers reflecting localized disc pathology.
• Further validation in larger, diverse cohorts is required to establish the diagnostic and therapeutic significance of these findings.
• The study provides a foundation for developing novel diagnostic tools and therapeutic strategies for DDD.