Protein-profiling identified potential biomarkers for the diagnosis of osteitis/osteomyelitis

Abstract

Background: A precise preoperative diagnosis of osteomyelitis is difficult and postoperative bacteriological and histopathological analyses are confirmatory. We therefore aimed at identifying differentially expressed proteins in the serum and tissue that distinguish healthy controls from acutely infected and chronic osteomyelitis. Such markers might serve for innovative early detection and could guide therapeutic intervention. Methods:We compared multiplex-fluorescence two-dimensional gel electrophoresis (2-DE)-based protein expression pattern of serum and tissue between healthy controls (n=9) and patients with acute (n=9) and chronic (n=9) osteomyelitis. 2-DE results were correlated by screening >9,000 serum auto-antibodies of the same patient cohort. Differences in expression levels between the three groups were statistically analyzed including principal component analysis (PCA). Results: Comparing the tissue-proteome of healthy controls and patients with acute and no chronic osteomyelitis (fold-change < 2.0 & p < 0.05), 105 differentially expressed proteins could be detected. Of those, 15 polypeptides were distinctly expressed between acute and chronic osteomyelitis. Interestingly, serum-based protein-profiling revealed a decreased similarity in protein expression - proportional to other twogroup comparisons - when comparing acute and chronic osteomyelitis. A PCA-based cluster analysis showed clustering and good separation between groups. Conclusion: This study showed significant differences in protein expression of osteomyelitis from healthy controls and from patients with acute and chronic inflammation. Targets will be identified by mass spectrometry and further validated for their biomarker potential on large patient cohorts.