Collaborators: Jill Jaycox, PhD
Aaron Ring, PhD, (Principal Investigator) is an associate professor of immunobiology at Yale University. His laboratory focuses on understanding and manipulating the activity of immune receptors using precision pharmacology and on applying methods in which desired traits are created through repeated rounds of genetic changes to create new pharmacological tools and therapeutics for the immune system.
Dr. Ring will examine autoantibody reactivities of ME/CFS patients using a technique called Rapid Extracellular Autoantibody Profiling (REAP). This study will build on previous work of autoantibodies in ME/CFS by using a technology and approach that will give this disease mechanism a much more in-depth investigation. Dr. Ring will also compare the ME/CFS data to a previously studied Long Covid cohort. A more rigorous investigation of a potential autoimmune component of ME/CFS could open the door to biomarkers and a host of therapies (for example, B-cell depleting drugs).
ME/CFS is a debilitating, multisystemic condition of uncertain etiology. However, evidence of immune system dysfunction, including the presence of autoantibodies, is well-established in ME/CFS patients. While some patients benefit from B cell – or antibody-depleting therapies, the role and significance of autoantibodies in ME/CFS pathophysiology is not well understood.
In this grant, we propose to use Rapid Extracellular Antigen Profiling (REAP) to comprehensively assess the autoantibody reactivities of ME/CFS patients against 4,200 extracellular human proteins and 50 pathogen antigens expressed in a yeast display library.
Then we will assess the biological functionality of these autoantibodies using ex vivo assays. With statistical modeling, we will ask whether specific ME/CFS reactivities correlate with clinical parameters or symptoms and whether autoantibodies can be used as a framework to subset patients within this heterogeneous diagnosis.
Overall, this work represents the first comprehensive and unbiased survey of autoantibody reactivities in ME/CFS. We believe our findings will generate novel insights into the role of humoral autoimmunity in ME/CFS pathophysiology.