The Gene Expression Analysis of Blood Reveals S100A11 and AQP9 as Potential Biomarkers of Infective Endocarditis

Abstract

BackgroundThe diagnostic and prognostic assessments of infective endocarditis (IE) are challenging. To investigate the host response during IE and to identify potential biomarkers, we determined the circulating gene expression profile using whole genome microarray analysis.Methods and ResultsA transcriptomic case-control study was performed on blood samples from patients with native valve IE (n = 39), excluded IE after an initial suspicion (n = 10) at patient's admission, and age-matched healthy controls (n = 10). Whole genome microarray analysis showed that patients with IE exhibited a specific transcriptional program with a predominance of gene categories associated with cell activation as well as innate immune and inflammatory responses. Quantitative real-time RT-PCR performed on a selection of highly modulated genes showed that the expression of the gene encoding S100 calcium binding protein A11 (S100A11) was significantly increased in patients with IE in comparison with controls (P<0.001) and patients with excluded IE (P<0.05). Interestingly, the upregulated expression of the S100A11 gene was more pronounced in staphylococcal IE than in streptococcal IE (P<0.01). These results were confirmed by serum concentrations of the S100A11 protein. Finally, we showed that in patients with IE, the upregulation of the aquaporin-9 gene (AQP9) was significantly associated with the occurrence of acute heart failure (P = 0.02).ConclusionsUsing transcriptional signatures of blood samples, we identified S100A11 as a potential diagnostic marker of IE, and AQP9 as a potential prognostic factor.

A systematic review of biomarkers in the diagnosis of infective endocarditis

“…The S100A11 transcript was upregulated in patients with IE compared to patients without IE [36]. Serum S100A11 protein was significantly higher in patients with IE compared to patients without IE and previous heart valve disease (5.0 ng/mL vs. 2.1 ng/mL, p b 0.05).…”

“…Secondly, Staphylococcus aureus (SA) IE showed significantly increased serum S100A11 compared to a healthy control group (p b 0.001). Additionally, the S100A11 transcript was significantly increased in SA-IE compared to Streptococcal IE (p b 0.01), but the protein was only slightly increased in serum, yet significant (p b 0.05) [36].…”

“…In a case-control study, S100A11 was identified as a potential biomarker of IE, using transcriptional signatures of blood samples to identify upregulated genes in peripheral blood [36]. The S100A11 transcript was upregulated in patients with IE compared to patients without IE [36].…”

Proteome Analysis of Coinfection of Epithelial Cells with Filifactor alocis and Porphyromonas gingivalis Shows Modulation of Pathogen and Host Regulatory Pathways

“…These nuclear envelope (NE) proteins act as regulators of MAPK, Wnt-␤-catenin, transforming growth factor ␤ (TGF-␤), and Notch signaling cascades (74). It is noteworthy that protein S100A11, implicated as a potential biomarker of infective endocarditis, was more abundant during F. alocis monoinfection (75). S100A11 proteins are involved in endocytosis and exocytosis (76), regulation of enzyme activity, cell growth regulation, apoptosis, and inflammation (77).…”

Polymorphisms Within Innate Immune Response, Calcium Metabolism and Lipid Metabolism Are Predictors of Infective Endocarditis

“…Более того, в группах риска летальность может достигать и 70% [29]. Развитие и клини-ческое течение ИЭ могут зависеть от: 1) опозна-вания патоген-ассоциированных молекулярных паттернов, цитокинового и острофазового отве-та [16,25,35]; 2) гемостаза [5,21,24]; 3) липидно-го [13,22] и кальциевого профиля плазмы крови [30,32]. Концептуально процессы воспаления, окисления липидов, кальцификации и гемоста-за в настоящее время рассматриваются как взаи-мосвязанные в рамках иммуновоспалительного континуума, одним из конечных звеньев кото-рого является кальцификация нативных и про-тезных клапанов сердца, ведущая к клапанной деструкции и недостаточности [28].…”