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

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Studying CSF to further reveal
pathogenesis mechanisms in ME/CFS

STUDY AIM
The goal of this research is to reveal more information about the role of immunology and neuroinflammation in ME/CFS, and the underlying mechanisms of related pathogenesis that takes place.
LEAD INVESTIGATORS
  • Jonas Bergquist, MD, PhD
  • Christopher W. Armstrong, PhD
UPDATES AND POTENTIAL
  • Collection of CSF samples and complementary plasma from ME/CFS patients in parallel to other neurological disorders (MS, ALS, HSE, TBI, etc.). 
  • Over 380 patients critically ill COVID patients enrolled with blood, urine, plasma samples collected for all, and CSF for those with severe neurological onset early in the disease.
  • 1,100 proteins have been detected in CSF.
  • 150 metabolites have been detected in urine.
  • In parallel, plasma metabolomics data (NMR + LC-MS) have been analyzed and resulted in close to 1,500 metabolites or metabolic ratios.
  • These data are undergoing computational analysis at Harvard and coordination with blood cell pellet data at Harvard and Stanford.

STUDY HYPOTHESIS AND DESCRIPTION

  • Underlying pathological mechanisms of ME/CFS are to a large extent unknown, but the presence of autoantibodies, cytokine pattern deviations and the presentation of cognitive and autonomic nervous system related symptoms indicate the role of immunology and neuroinflammation in the pathogenesis of the disease. 
  • Studying cerebrospinal fluid (CSF) could specifically provide information of the pathological processes occurring in the central nervous system.

OBJECTIVES

  • Collect CSF and plasma from ME/CFS patients.
  • Conduct in-house quantitative proteomics and metabolomics analysis.
  • Share data with collaborative groups that want to analyze the CSF more in detail.
  • Collect CSF and plasma from people with other neurological diseases (including Parkinson’s, Multiple Sclerosis, Alzheimer’s, Herpes Simplex Encephalopathy,  Neuro-covid etc) and compare to ME/CFS.
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.
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.
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.
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.