Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Post COVID .

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Autoimmunity and
Autoantibodies in ME/CFS

Study AIM

Investigate potential differences in adrenergic and muscarinic receptor autoantibody levels in plasma and cerebrospinal fluid (CSF) samples between ME/CFS patients and healthy controls, examine why these autoantibodies start to show up in the disease process and how we might positively impact this process with various drug targets and immune regulatory treatments. Being able to explain these underlying mechanisms may provide the validation needed for specific ongoing treatments.

LEAD INVESTIGATORS
  • Jonas Bergquist, MD, PhD, Prof, Director ScD
  • Annie Bynke, Med Student, PhD
  • Per Julin, MD, PhD , MD
  • CG Gottfries, MD, PhD, Prof em
  • Carmen Scheibenbogen, MD, PhD, Prof
Updates and Potential
  • Completed validation study on the presence of autoantibodies in plasma in two Swedish ME/CFS cohorts, and paper published.
  • Observed a significant up-regulation of autoantibodies in up to 70% of patients. Significantly increased autoantibodies against adrenergic and muscarinic receptors have been found in the plasma of ME/CFS patients.
  • No autoantibodies could be found in CFS, which is positive news as that would make the removal of autoantibodies very difficult.
  • Preliminary studies using immunoadsorption and / or plasmapheresis to remove autoantibodies show positive effects in at least a sub-population of ME/CFS patients.

Collection of data from expanded ME cohort and COVID cohort ongoing and should be ready for evaluation in fall 2023. Analysis in Berlin planned for.

STUDY HYPOTHESIS AND DESCRIPTION

The development of autoimmune antibodies is a consistent finding across HSE, ME/CFS, Long COVID and provide a window into the neurocognitive disturbances, peripheral symptoms, POTS, pain, and other targets of these autoantibodies.

Previously, autoantibodies have been observed to have increased binding to adrenergic and muscarinic receptors in ME/CFS patients. It is hypothesized

that these autoantibodies may be part of the pathogenesis of ME/CFS and patient symptom.

OBJECTIVES

Plasma, CSF and health-related questionnaires were collected from two Swedish ME / CFS cohorts, plasma and CSF from one of the cohorts (n=24), only plasma from the second cohort (n=24) together with plasma samples (n=24) and CSF (n=6) from healthy controls.

All samples were analyzed for IgG autoantibodies directed against adrenergic and muscarinic receptors ELISA technique. The questionnaires were used as measures of disease severity.

This study has been published in Brain, Behavior and Immunity – Health

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Microvesicles and viral sequencing
Microvesicles are a type of extracellular vesicle that is released from the cell membrane. Vesicles are small, fluid-filled sacs or vacuoles within the body. Sequencing is a technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA (or viral) molecule.
NMR Metabolomics
NMR (Nuclear Magnetic Resonance) is an instrument/tool used to perform metabolic studies, metabolic profiling, and metabolomics in biofluids and tissues for more than 40 years using magnetic fields. There is a very close connection between metabolic measurements and NMR. This connection has flourished because of NMR’s many unique strengths for characterizing complex mixtures’ chemical composition.
Proteomics
The large-scale study of proteins, which are large, complex molecules that are required for structure, function, and regulation of the human body's tissues and organs.
Immune cell profiling
The immune system has many important regulatory roles in disease development and progression. Given the emergence of effective immune therapies, reliable predictors of response are needed. Immune cell profiling determines response by evaluating immune cell populations from treated and untreated samples. For our purposes, we will evaluate the white blood cell response to the viral infection using a process called “Cytof.”
Leukocyte Genomics
A leukocyte is a colorless cell circulating in the blood and body fluids and is involved in counteracting foreign substances and disease. A genome is all genetic material of an organism. Genomics is a biology field focusing on the structure, function, evolution, mapping, and editing of genomes. Therefore, leukocyte genomics is the study of all genetic material of leukocytes.
Metabolomics
Metabolomics is a way to study metabolism – that is, through measuring amounts of the metabolites (small molecules) produced by our bodies as we convert food into energy and other molecules that our cells need to survive. Metabolomics technology is ‘large-scale,’ meaning that several thousand metabolites can be measured from a single sample of e.g., blood or urine.
Micro RNA
Cells use Micro RNA to control whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.
Autoantibodies
Antibodies that react with self-molecules and that occur in healthy individuals and are referred to as natural antibodies or autoantibodies.
Extracellular DNA for viral reactivation and Mitochondrial DNA
exDNA (extracellular DNA), exDNA is often secreted actively and is used to perform several tasks, thereby offering an attractive target or tool for biotechnological, medical, environmental, and general microbiological applications. Viruses are intracellular parasites that rely to a significant extent on the host cell for replication. Viral reactivation occurs when an active replication of the viral genome results in a lytic (degradation of the cell) infection characterized by the release of new progeny (descendant) virus particles.