Diagnostic potential of immune serum proteins in Osteosaropenia identified via proximity extension assay

Abstract

Background: Osteosarcopenia, characterized by coexistence of osteoporosis and sarcopenia, is influenced by immunological dysfunction and systemic inflammation, however their specific roles remain unclear. This study aimed to investigate inflammation-related serum profiles in osteosarcopenia using the Proximity Extension Assay (PEA).

Methods: Overall, 50 participants with a history of falls and fractures were recruited and classified into three groups, controls, sarcopenia, and osteosarcopenia. Oseteosarcopenia was diagnosed in individuals with both functional sarcopenia and osteoporosis. Functional sarcopenia was diagnosed according to the Korean Working Group on Sarcopenia guidelines. Osteoporosis was defined as a T-score of the areal bone mineral density (aBMD) of the femoral neck ≤ -2.5. Serum inflammatory protein levels were quantified using the Olink® PEA inflammation panel, targeting 92 proteins.

Results: Twenty inflammation-related proteins were identified as differentially expressed proteins (DEPs), and 33 proteins showed significant correlations with clinical measures of muscle function or aBMD of the total hip, femoral neck or lumbar spine. Weighted Gene Co-Expression Network Analysis (WGCNA) identified 27 proteins with significant module membership and contribution to group separation. Notably, four proteins, including SLAMF1, OPG, FGF-23, and CSF-1 were DEPs, significant in WGCNA, and correlated with clinical variables. Principal component analysis and heatmap analyses revealed osteosacropenia as a distinct entity, differing from sarcopenia and controls. Bioinformatics suggested that T cell modulation and tumor necrosis factor binding capacity play significant roles in osteosarcopenia development.

Conclusions: Osteosarcopenia exhibited unique immune-related profiles distinct from those of sarcopenia and controls, emphasizing the potential role of inflammation and adaptive immunity in its pathogenesis.