Diagnostics

The aim of the Sangui Bio diagnostics research is to explore the clinical utility of our novel discoveries involving red blood cells (RBCs) as reservoirs for signalling molecules. Proteins such as cytokines are candidate biomarkers for diagnostics and for monitoring therapeutic responses because of their roles in inflammation, immune response, and repair. Our research indicates that these RBCs are acting as a ‘buffer’ of signalling proteins against extremes of concentration, thereby modulating immune activity. Dysfunction in this system during disease may contribute to progression and may also be an ideal target for diagnostic development. We have been investigating this dysfunction in a variety of inflammatory diseases including pre-eclampsia and cancer.

Cancer

Inflammatory biomarkers are associated with worse outcomes in numerous cancers and have been a focus of cancer research in many studies.  We are initially assessing plasma and RBC biomarker levels (cytokines and cancer specific markers) in male and female cancer patients.  We have observed differences in the RBC lysate protein profile isolated from pre-treatment cancer patients compared to healthy controls. A number of these differences were not detectable in the plasma fraction, but were observed in the RBC lysate (Figure 1). These results highlight the value in analysing multiple fractions of blood in disease. We are planning to compare these marker profiles with the distribution of inflammatory cells including T-cell subsets including CD8+ T-cells, CD4+ T-cells, natural killer cells, regulatory T cells, and immature myeloid cells by flow cytometry.

Figure 1. Concentration of cytokines in the plasma or red blood cell lysates in one millilitre of whole blood collected from healthy individuals or individuals with cancer.

Figure 1. Concentration of cytokines in the plasma or red blood cell lysates in one millilitre of whole blood collected from healthy individuals or individuals with cancer.

Pre-eclampsia

We have observed differences in RBC and protein release profiles between cells isolated from women with pre-eclampsia and those from women with gestationally aged-matched healthy pregnancies (Figure 2). These differences were most notable with the inclusion of our proprietary protease inhibitor cocktail during incubation. Our current research is focused on establishing which cytokines and other proteins are most predictive of the disease. We are planning to complete a prospective pilot study in women with gestational hypertension (of whom 30% will develop the life-threatening complication, pre-eclampsia) to see if this approach can differentiate between benign hypertension or the life-threatening form – pre-eclampsia.

Figure 2. Concentration of cytokines released from red blood cells treated with protease inhibitors during overnight incubation. Red blood cells were isolated from healthy pregnant women or women with pre-eclampsia.

Figure 2. Concentration of cytokines released from red blood cells treated with protease inhibitors during overnight incubation. Red blood cells were isolated from healthy pregnant women or women with pre-eclampsia.