Nearly every illness includes an inflammatory aspect, but current blood tests can’t specifically identify inflammation in particular organs or tissues. Recently, scientists have created a new technique involving antibodies that may lead to blood tests for biomarkers associated with specific diseases like heart disease, Alzheimer’s, and various types of cancer. This breakthrough also offers exciting prospects for discovering new medications.
Almost every illness has an inflammatory aspect, but blood tests are unable to identify inflammation in specific organs or tissues in the human body.
Researchers from Case Western Reserve University have introduced a new method for detecting inflammation through antibodies, which might facilitate blood tests for specific disease biomarkers, including those for heart disease, Alzheimer’s, and several types of cancer. Their finding also shows potential for enhancing drug discovery.
Greg Tochtrop, a chemistry professor at Case Western Reserve, stated, “This research opens up a fantastic array of opportunities for future exploration. It will directly contribute to a better understanding of inflammation and disease detection, as well as the development of new pharmaceuticals.”
This research, led by Tochtrop, was published today in the journal Proceedings of the National Academy of Sciences (PNAS).
Inflammation leaves a trace
Tochtrop found that certain compounds produced from the reaction with reactive oxygen species (ROS)—highly reactive chemicals that can harm DNA, proteins, and lipids—exhibit a distinctive reactivity that allows for detection using antibodies.
During inflammation, immune cells generate ROS to destroy bacteria and other pathogens. ROS can also be produced due to environmental influences such as UV light, pollution, radiation, and smoking. Excessive ROS can lead to cell and tissue damage.
Tochtrop and his team explored how ROS reacts with linoleic acid, a fatty acid present in all cell membranes, resulting in compounds that can attach to RNA, DNA, and proteins, known as epoxyketooctadecanoic acids (EKODEs).
Tochtrop found that EKODEs bind to the nucleic acid cysteine in a novel way, creating a stable bond. These compounds accumulate in tissues experiencing oxidative stress, such as the brain, heart, liver, and other organs. From mouse models, Tochtrop developed antibodies to these EKODEs and was able to identify different types of EKODE buildups in various tissues in both mice and humans.
“What makes this particularly intriguing and potentially significant,” Tochtrop remarked, “is our ability to detect unique compounds and their concentrations in different tissues and organs, suggesting that we might detect various diseases through a blood test.”
The proposed test could be akin to the A1C test for diabetes, which assesses the portion of hemoglobin coated with glucose, reflecting glucose levels over the past three months. An EKODE test could indicate abnormal oxidative stress in specific organs.
Pursuing disease-specific biomarkers
Tochtrop emphasized that the next phase involves locating different EKODE targets in specific organs and tissues to correlate these biomarkers with particular diseases. He is especially interested in EKODEs found in the eye that respond to age-related macular degeneration or diabetic retinopathy affecting vision.
Tochtrop clarified why these biomarkers have previously gone unidentified: “We needed to create many of the laboratory tools necessary to search for them in the first place,” he explained.
The researchers produced EKODE model compounds and examined how they interacted with various amino acids, discovering that cysteine is the only amino acid that EKODE binds to for any significant duration.
“By studying the inherent chemistry of the system, we predicted what could form and then searched for those compounds,” he said. “There are crucial translational implications, and this exemplifies how a foundational approach can guide the subsequent steps in developing clinical tests.”
Opportunities for new drug discovery
This research could also support drug discovery, as pharmaceutical developers seek reactive cysteines.
“Finding reactive cysteines is pivotal in current drug discovery,” he mentioned. “This could reveal numerous reactive cysteines that can be targeted for drug development, making this an important aspect of our research.”
