Researchers from Case Western Reserve University have now developed a method for detecting inflammation using antibodies, which may lead to the creation of blood tests for specific disease biomarkers, such as heart disease, Alzheimer's disease, and various types of cancer. Their achievement also opens up prospects for drug discovery.
Yesterday, the results of this study were published in the journal Proceedings of the National Academy of Sciences (PNAS), paving the way for numerous future developments.
“Our discovery directly contributes to a better understanding of inflammation and disease identification, as well as the development of new medications,” said the study's lead researcher Greg Tochtrop, a professor of chemistry at Case Western Reserve.
Inflammation Leaves Traces
Tochtrop found that certain compounds formed through interactions with reactive oxygen species (ROS) — highly reactive oxygen-containing chemicals capable of damaging DNA, proteins, and lipids — respond in a completely unique manner, allowing their detection using antibodies.
During inflammation, immune cells produce ROS to eliminate bacteria and other pathogenic microorganisms. ROS can also be generated by environmental factors such as ultraviolet radiation, pollution, radiation, and smoking. An excess of ROS can damage cells and tissues.
Tochtrop and his colleagues investigated how ROS reacts with linoleic acid, which is found in all cell membranes, forming compounds that can bind with RNA, DNA, and proteins, known as epoxy-keto-octadecanoic acids (EKODAs).
Tochtrop discovered that EKODAs interact with cysteine in nucleic acids in a previously unreported way, forming stable bonds. These compounds then accumulate in tissues suffering from oxidative stress, such as the brain, heart, liver, and other organs. Tochtrop developed antibodies against these compounds in mouse models and was able to detect the accumulation of various types of EKODAs in different tissues, both in mice and humans.
“What makes this method so interesting and potentially valuable,” says Tochtrop, “is that we can detect unique compounds and their concentrations in various tissues and organs, which means that it may be possible to identify a wide range of diseases with a single blood test.”
The inflammation test is reminiscent of the glycated hemoglobin test for diabetes, which measures the concentration of hemoglobin coated with glucose, reflecting the level of glucose circulating in the blood over the past three months. The EKODA test can identify deviations in the oxidative stress system in specific organs and indicate where inflammation has developed in an organ or tissue.
Searching for Disease-Specific Biomarkers
According to Tochtrop, the next step will be to identify various targets of EKODAs in individual organs and tissues to correlate biomarkers with specific diseases. He is particularly interested in EKODAs produced in the eyes in response to age-related macular degeneration or diabetic retinopathy, which affect vision.
Tochtrop explained why these biomarkers had not been previously identified: researchers had to develop many new tools in the lab to detect them.
Potential for Discovering New Drugs
This research may also aid in drug discovery, as the identified reactive cysteines could become targets for drug development, which is a valuable outcome of this study.