Uncovering Biomarkers – Fcg receptors in ME/CFS
Uncovering Biomarkers – Is protein dysfunction a risk factor for the development of ME/CFS?
The Bateman Horne Center (BHC) is determined to bring ME/CFS and FM into the mainstream by focusing on the discovery of biomarkers. Biomarkers will improve diagnosis and treatment and put us on a pathway to a cure. It is the powerful combination of an active and specialized medical center of excellence with an innovative research program, under one roof, that allows us to most effectively focus on this work.
To achieve our goal of finding a biomarker we are recruiting a Research Ready Army of well-defined patients eager to participate. Our Research Ready Army helps drive the discovery of biomarkers by participating in a comprehensive clinical evaluation, answering questions, and providing blood samples. This valuable and secure data is in turn shared with top scientists – each working on different potential biomarkers – like Dr. Isabel Barao, a cancer immunologist and ME/CFS researcher at the University of Nevada, Reno (UNR).
In this guest blog, Dr. Barao explains the research she is doing to uncover potential immune system dysfunction in ME/CFS as a potential biomarker.
Fcg receptors (FcγRs) in ME/CFS
by Dr. Isabel Barao
A number of symptoms of ME/CFS are linked to immune dysfunction. An Fc Receptor (FcR) is a protein found on the surface of certain cells that contributes to the protective functions of the immune system. I hypothesized that FcR protein dysfunction is a risk factor for the development of ME/CFS.
In a healthy immune system, Fc Receptors (FcRs) bind to antibodies that are attached to infected cells or invading pathogens, stimulating other certain cells to destroy the infected ones. There are several different types of FcRs, each one classified by the type of antibody they recognize. Those that bind the most common class of antibody, IgG, are called Fc-gamma receptors or FcγRs.
FcγRs are responsible for the effective control of both B cells (a type of white blood cell) and natural killer cells (NK cells), a critical part of a person’s immune system. NK cells are central to generating appropriate responses to infection and preventing autoimmunity. When this balance is lost, there is an increased susceptibility to cancer, autoimmunity, and infection. In contrast, optimal FcgR activity facilitates effective disease resolution and response to immunotherapy. The underlying genetics of the FcgR gene family are a central component of this balance.
Because a number of symptoms of ME/CFS are linked to immune dysfunction, I have hypothesized that FcγRs are risk factors for the development of ME/CFS. My research has been focused on the biology of lymphocytes and in the design of effective immunotherapies to treat disease. NK cells are the first defense against viruses and cancer and NK cell deficiency occurs in ME/CFS. Patients have an increased susceptibility to infections and increased risk of developing non-Hodgkin lymphoma.
I am trying to determine if there is abnormal NK cell functioning in ME/CFS patients. NK cells express FcgRs and these receptors recognize and bind to the antibody which has bound to the surface of an infected or cancer cell. Once the FcgRs bind to the antibody, the NK cell is activated and releases lytic proteins, which causes the death of the infected or cancer cell. This is called antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC capability of NK cells in ME/CFS patients is unknown.
In collaboration with the Bateman Horne Center, the National Cancer Institute (NCI) at NIH, and Roche Pharmaceuticals, my UNR colleagues and I are examining mutations in NK cells of ME/CFS patients and their associations to ADCC capability and disease pathology. The team is committed in defining ME/CFS clinical subtypes through FcgRs immune profiling and in developing immunotherapies to treat the disease.
This research has been supported by NIH (CTR-IN 1U54GM10444-2 and R21AI117491), Simmaron Research, Inc., Solve ME/CFS Initiative, and private donors. The first manuscripts are in preparation.