Biomarker signatures of biological, chemical, or psychological stress
David A. Lawrence
It is hypothesized that human exposures to environmental stresses (biological, chemical, physical and psychological) result in alterations to the neuro-endocrine-immune axis. These changes provoke shifts in molecular components of the blood that reflect changes in biomarker levels. Septic patients and rheumatoid arthritis patients can be used as prototypes for stressed individuals to identify and quantify the presence of serum proteins that have increased, decreased, or which display epitope-modified expression. These molecular features will form the basis of specific biomarker signatures that are characteristic of stressed human individuals.
Preliminary experiments document that biological, chemical, and psychological stress alters plasma protein expression levels, which in part are due to inflammation and/or oxidative processes. Because we suggest the different forms of stressors modulate the interactive pathways between the endocrine, immune and nervous systems, we anticipate that immune, endocrine, and nervous system factors will be predictors of stress and that the profiles of these factors will provide prognosis for the degree of stress and the severity of the exposure.
Individual biomarkers predicted to relate to regulatory pathways associated with inflammation, anti-inflammation, oxidants, anti-oxidants, and innate immune processes are quantified in humanized mice after exposure to three prototype stressors: cadmium, cold-restraint, and listeria infection. We delineate and quantify the normal basal and responsive plasma concentrations of relevant biomarkers and we validate their analysis with a new biosensor employing grating-coupled surface plasmon resonance imaging (GCSPRI).
GCSPRI is a microarray platform that enables the multiplexed detection of these biomarker signatures with an automated diagnostic system in near real time. In addition to stressor-induced changes in plasma constituents, we will evaluate changes to blood leukocyte antigens; lymphocytes are especially sensitive to inflammatory products and oxidants.
Blood products are obtained with minimal invasiveness, and they represent the best composite of the systemic response to a stressor. The GCSPRI technology has also been parallel tested against Luminex technology. The biomarkers evaluated include blood clotting factors, cytokines, stress proteins, neuropeptides, antioxidant enzymes, and normal plasma proteins with thiol-related modifications. We have evaluated the consequences of different stress response capabilities on the character of the biomarker signatures identified in this work. This has allowed us to identify specific biomarker signatures that are both diagnostic of specific signatures and highly valuable in diagnosis of stress and the characterization of therapeutic management of stressed individuals.