Exploring an anti-citrullinated antibody signature in ME/CFS

Principal Investigator

Prof. Mercedes Rincon


College of Medicine, University of Vermont, Burlington, Vermont, USA

Start date

April 2019

Background and aim

Prof. Mercedes Rincon is Professor of Medicine at the University of Vermont, and the research group she heads is interested in the molecular mechanisms underlying autoimmune diseases. Prof. Rincon also has an interest in ME/CFS, and her co-investigators include Prof. David Maughan, whose wife, Cathleen, has had the illness for the last twenty years.

Spurred on by this personal involvement, the group has conducted previous research looking at the immunological basis of ME/CFS, including the detection of specific autoantibodies that target citrullinated proteins. Their new study, funded by ME Research UK, aims to confirm these preliminary findings in a larger group of patients.

Autoantibodies occur when the immune system wrongly identifies the body’s own healthy cells as harmful, and produces antibodies against them. This can lead to the development of a so-called autoimmune disease such as multiple sclerosis or lupus. Recent findings suggest that autoantibodies may also have a role in ME/CFS, at least in some patients.

Prof. Rincon explains, “Citrullination is a protein modification that can happen sometimes in response to some infectious agents. Citrullination makes a ‘self protein’ become a ‘foreign protein’, and therefore recognised by the immune system. This leads to the generation of antibodies against those citrullinated changes.”

Such anti-citrullinated antibodies have been detected in rheumatoid arthritis—itself an autoimmune disease—where they have a pathological role and are used in diagnosis.

The characteristics of ME/CFS suggest the involvement of autoantibodies in that illness, and Prof. Rincon’s team plans to look specifically for autoantibodies targeted on citrullinated proteins. Using blood samples obtained from the UK ME/CFS Biobank, the researchers will compare autoantibody levels between ME/CFS patients and a group of healthy control subjects.

These results will also be compared with those from patients with multiple sclerosis—another known autoimmune disease—and compared with previous findings in patients with rheumatoid arthritis.

The outcomes of this study could provide valuable insight into the pathophysiology of ME/CFS, and the potential involvement of autoimmunity in the illness. They may also help to identify effective treatments, and to provide the basis for further research looking at specific sites of citrullination and targets for intervention.