Meet The Researchers  |  About the Ramsay Award Program  |  Impact  |  Applying for an Award  |  Contact


Dr. Jonas Blomberg and Dr. Jonas Bergquist

Biomarkers for initiation (infection) and metabolic derangement in ME/CFS”
PI: Jonas Blomberg, MD, PhD, Jonas Bergquist, MD, PhD

Uppsala University in Sweden

Dr. Jonas Blomberg (MD, PhD) and Dr. Jonas Bergquist (MD, PhD) from Uppsala University put together an interdisciplinary effort using advanced quantitative methods to probe an autoimmunity pathogenesis (onset and development) of ME/CFS. Using serology (analyzing antibodies in blood), the group is looking for indications of past infections in patients and examining the possible connection of autoantibodies (antibodies produced by the immune system that mistakenly target a person’s own proteins) to deficiencies in energy production. The team is further strengthened by collaboration with the Gottfries Clinic, a dedicated ME/CFS and fibromyalgia outpatient clinic in Mölndal, Sweden. Carl-Gerhard Gottfries (MD, PhD), and Olof Zachrisson (MD, PhD), bring extensive clinical expertise of ME/CFS, enhancing the translational research goals of the study.

Remembering Dr. Jonas Blomberg

Dr. Jonas Blomberg, a leading virologist in Sweden deeply involved in moving ME/CFS research forward, passed away in February 2019. His many valuable contributions to the field were amplified by his collaborative, interdisciplinary approach and a passionate dedication to people with ME/CFS.

A prolific researcher, Dr. Blomberg devoted much of his career to the study and characterization of human retroviruses using bioinformatic approaches. He developed powerful multiplex methods to study pathogens and applied this methodology to the study of ME/CFS. He was twice funded through SMCI’s Ramsay Award Program to examine infectious triggers, autoimmunity, metabolic abnormalities and biomarkers of mitochondrial dysfunction and signaling in ME/CFS.

The scope of his involvement went far beyond the research bench. He served on the Board of Directors of the Gottfries Clinic in Sweden and as an advisor to the Open Medicine Foundation. Dr. Blomberg was also a member of the Biomarkers Working Group of EUROMENE, a European organization that seeks to increase collaboration and funding for ME/CFS research in Europe.

 

Major Ramsay goals fulfilled:

✓ Added to the cumulative, scientific knowledge. The hypothesis paper “Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model” was published in Frontiers in Immunology in XXXX. Read it here. The research team also published findings that ME/CFS patients across three cohorts had the same risk of being infected with a human herpesvirus as healthy controls. Subtle differences in the readout suggest complex interactions of herpesvirus with the immune system might differ in people with ME/CFS. Read the study here.

Watch an interim update from Dr. Bergquist here

Read the research study abstract below:

 

Our working hypothesis of ME/CFS pathogenesis is that a person predisposed for ME through genetics and previous antigen exposure is infected with a microbe prone to elicit ME. These microbial antigens have epitopes which cross-react with self-epitopes. An (auto)immune response to this microbe which bypasses tolerance mechanisms is elicited. The cross-reactive immune response, e.g. autoantibodies, is directed against molecules involved in energy metabolism, hormonal regulation and, possibly, specific portions of the brain. In short, “infection elicited autoimmunometabolic dysfunction”.

The role of infection may either be a “hit and run” phenomenon, or a chronic infection (“stay and fight”). We investigate the hit and run alternative by serology, looking for microbial antibodies, which allows retrospective detection of past infections of an ME/CFS patient. This approach also has the potential of revealing microbial antigens which cross-react with self-epitopes, a plausible origin of autoimmunity. The group of professor Jonas Blomberg already detected antibodies to a mitochondrial antigen, heat shock protein 60, which occurs both in microbes and human cells. We will continue this line of investigation, looking for more evidence of collusion between anti-microbe and anti-self in ME. Depending on financial means we will also look for evidence of chronic infection (“stay and fight”), the other form of human-microbe Interaction. We will then develop and use sensitive broadly targeted PCRs for viruses, bacteria and protozoa in the blood of ME/CFS patients.

Autoantibodies directed against energy-producing organelles like mitochondria are a plausible cause of PEM {Post Exertional Malaise), the cardinal symptom of ME/CFS. Recent research findings indicate a block of transition from anaerobic {also known as glycolysis) to aerobic energy production in
ME/CFS. The block manifests itself by an increase of metabolites before the block {e.g. lactate), and a decrease of metabolites after the block (e.g. succinate and alternative pathways like lipids and some amino acids). The nature of this block can be better understood by further studies on energy metabolites. Professor Jonas Bergquist has a unique set of quantitative methods for them. The purpose is to corroborate previous findings, and to reveal details of the metabolomic disturbance in ME/CFS.
We are fortunate to collaborate with the most experienced ME/CFS clinic in Sweden, the Gottfries clinic, in Mölndal. Prof. Carl-Gerhard Gottfries and Dr. Olov Zachrisson provided us with a collection of 198 blood samples from anonymous ME/CFS patients and controls. Their extensive clinical experience of ME/CFS is a guarantee for the clinical relevance of our research. Appropriate ethical permissions are at hand. The ME/CFS patients were diagnosed using the stringent Canadian criteria.
The laboratories of Jonas Bergquist and Jonas Blomberg in Uppsala are uniquely suited for a collaborative effort to better understand the pathogenesis of ME/CFS, and to develop biomarkers for the disease.