Physicians lack effective tools to aid in the diagnosis and treatment of those who are impacted by ME/CFS, a complex and often disabling disease. That could change now that scientists at Nevada Center for Biomedical Research (NVCBR) have taken the first step in developing a clinical assay for diagnosing ME/CFS patients through the creation of an antibody immune signature.

The work was conducted in collaboration with Drs. Stephen Johnston and Phillip Stafford, at Arizona State University’s Biodesign Institute, Innovations in Medicine, and Drs. Karen Schlauch and Richard Tillet, from the University of Nevada, Reno, as well as other researchers from around the world.

The group’s findings recently appeared in the prestigious journal Molecular Neurobiology https://link.springer.com/article/10.1007/s12035-016-0334-0

The immune system produces proteins called antibodies that bind to the surface of pathogens, such as viruses and bacteria, to neutralize the pathogens. Occasionally, this system becomes dysregulated and produces antibodies to our own tissue, resulting in autoimmunity. Utilizing a microchip comprised of thousands of small random protein sequences (referred to as random peptides), researchers at NVCBR, in collaboration with the scientists at ASU’s Biodesign Institute, screened blood sera from ME/CFS cases and healthy controls, from two geographic distinct cohorts, and identified a diagnostic pattern of antibody/peptide binding that identifies ME/CFS patients with high specificity and sensitivity.

“The purpose of screening sera with a random peptide array is to identify things that our body sees as foreign such as the molecules that make up pathogens or the proteins of our own tissue, in the context of autoimmunity,” explained Dr. Vincent Lombardi, NVCBR Research Director. “Now that we have identified a group of random peptides that differentially bind with the antibodies of ME/CFS patients, our next challenge is to figure out what antigens these random peptides represent in the real world. Much can be learned about the causes of this disease once the antigens are accurately identified.”

Dr. Lombardi originally conceived of the project with the aim of identifying potential pathogens associated with ME/CFS as well as autoantigens. In addition to identifying prospective pathogen-associated antigens and autoantigens, the data also produced an immunosignature that can accurately identify ME/CFS patients from healthy controls. Future in-depth analysis of these data will help researchers determine which antigens are most relevant to the disease process and whether or not there are existing treatments available to target the implicated biochemical pathways.

Going forward, NVCBR researchers intend to confirm the work using a larger ME/CFS cohort as well as other disease cohorts with overlapping symptomology such as multiple sclerosis. The immunosignature technology, developed by ASU, has been used successfully with other neuroimmune diseases including Alzheimer’s disease.

“The goal of our research program is to ascertain the underlying mechanisms of neuroimmune disease as well as identify disease-related biomarkers and more effective treatments for the patients,” stated Dr. Lombardi. “A robust immunosignature of ME/CFS would help achieve these goals.”