I consider an encounter with a patient on the verge of dying due to a severe case of infection as one of my most humbling experiences as an internist. As part of routine care, I gave the patient the most effective drug under the circumstances, the most recommended hydration, and the best care. But I was helpless. Deep inside, I knew that the patient would likely die.
Sepsis, or severe infection, is a major cause of death worldwide. It is the number one cause of death for children less than one year of age, and a major cause of death in adults. About one-third die of complications that result from low blood pressure resulting in damages in the key organs of the body, such as the kidney, lever, heart, lungs, and brain.
Despite all the clinical efforts in the past 30 to 40 years, the mortality of sepsis did not significantly improve. Scientists and clinicians remain perplexed by the lack of improvement in clinical outcomes despite targeting the usual molecular suspects – the inflammatory players, the vascular molecules, or the infectious particles.
One possible light at the end of the tunnel emerged when, in 2009, a finding that self-generated histones from our own dying cells (our own protein) are the very ones that would eventually injure our blood vessels. Histones are proteins that fold the DNA in our cells. This leads to the loss of plasma from our blood that can lead to lowering of blood pressure, which starts a vicious cycle leading to serious complications and health.
The use of antibodies to protect humans from illnesses is not new. Anti-tetanus injections are common for trauma victims. Anti-rabies and anti-hepatitis are provided after a suspect post-exposure to the viruses. With these in mind, is it possible to do this in severe infection?
In previous years, the use of antibodies in infection is only limited to the disease-causing bacteria or virus. With the findings of the article on histones, two things became clear: we can target the histones and we can use antibodies.
Thus, we made a specific effort to see if chicken egg antibodies, called IgY, would be effective. We generated human histone-specific antibodies from vaccinated hens.
We isolated and purified them so that other substances and antibodies not specific to the histones were removed. The antibodies were proven to be safe, as mice and rat injected with high dosages survived after one to two weeks. However, for efficacy, results only showed a trend towards effectiveness by lowering mortality in treatment groups compared with the control groups.
These findings do not conclusively demonstrate effectiveness. Nevertheless, the implications are important. First, it demonstrates that chicken egg antibodies, which are several-fold cheaper and easier to isolate, are safe for therapeutic use. Second, the mere fact that we have purified antibodies implies that such antibodies are also useful in the detection of blood histones in patients with severe infection, a direction that we intent to follow-up.
Written by: Dr. Jose Nevado Jr. and M. Monaliza Miras University of the Philippines Los Banos Published by:Department of Science and Technology-Science and Technology Information Institute (DOST-STII)