An Objective Blood Test from Stimulated Gene Expression for Classification and Outcome Assessment in Clinical Trials of Gulf War Illness
Abstract
Gulf War Illness (GWI) has proven to be an extremely difficult condition for medicine to address, primarily because of the great difficulty of defining it so that the most powerful techniques of modern medical research can be brought to bear on it. Over the past 20 years, our research group has taken the important steps of developing a clinical case definition constructed from three unique patterns of symptoms that define three important subgroups, or GWI variants. This clinical definition of GWI has now been proven in three independent studies and in a succession of research studies using brain imaging, brainwave testing, and traditional neurological tests. Two years ago, the Defense Department funded our pilot study of our bold plan to develop an objective blood test for GWI and its three variants using a cutting-edge research technique called "gene expression analysis." This involved the relatively inexpensive testing of blood samples we had collected in two prior studies to measure the level of functioning of the tens of thousands of genes found in white blood cells and doing a complex computer search for a pattern of gene functioning that was either abnormally high or abnormally low in Veterans with GWI compared to the Veterans who remained well. Finding highly discriminating patterns of gene functioning could be developed into a simple blood test that could be used to make a diagnosis of GWI with classification into the three variants. Our use of the available blood samples that could be tested inexpensively in the pilot study identified a potentially important cancer-causing gene expression pattern that might identify Veterans at higher risk of developing various cancers, but the blood samples were not adequate for the more demanding task of finding a diagnostic test for GWI. We are therefore proposing an extension to the pilot study to collect fresh blood samples suitable for this more complex goal. In this extension study, we will bring to our research university in Dallas the approximately 140 Gulf War-era Veterans who have participated in two of our past clinical studies of GWI. In our laboratory, we will collect fresh blood samples and immediately use a sophisticated blood cell sorting machine to separate out a certain type of white blood cell called T lymphocytes, or simply T cells. Producing pure samples of T cells removes the large amount of "noise" from the many other types of white blood cells that complicated our prior pilot study. Next, we will divide the T cell sample into two subsamples and treat each with a different chemical that is known to stimulate the genes of white blood cells to bring out subtle differences in gene function. Many previous studies of gene functioning have used this type of chemical stimulation to make important discoveries about other diseases. From there, we will proceed with sophisticated laboratory measurements of gene functioning on the two T cell subsamples as we did in our prior pilot study that identified the cancer-causing gene pattern. This cutting-edge measurement process measures two important kinds of gene-functioning products: large messenger RNAs and small micro-RNAs. Measuring both types of RNAs in the same study gives us twice the chance of finding a pattern that will translate into a diagnostic test. In the last several years, these two types of gene functioning products have been used successfully to develop new disease tests and treatments for various diseases. The approach that we are proposing for our extension study has a high likelihood of success within only 3 years for several reasons. First, our recently completed pilot study showed that our laboratory methods are capable of identifying important gene expression patterns in blood of GWI patients. Second, we learned from our pilot study the types of blood collection and processing refinements we need to make to be able to see the more subtle gene expression patterns that will different
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510672
Entities
People
- Robert W. Haley
Organizations
- United States Army
- University of Texas Southwestern Medical Center