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Home NEWS/Research

A Review of Dr. Gordon Broderick's article on biomarkers for CFS

by Kathryn Lycett

The article being reviewed is  "Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue" by Gordon Broderick, Ben Z.Katz, Henrique Fernandes, Mary Ann Fletcher, Nancy Kilmas, Frederick A. Smith, Maurice RG O'Gormon, Suzanne D Vernon and Renee Taylor.

Read the first two References below: Biomarkers in CFS and Immune System to help understand the terminology.

My report is a synopsis of the highlights.

The research involved a clinical investigation of people who did not recover from illness several years after an infection. Their  persistent symptoms included fatique, sleep disturbance and cognitive impairment. The post infection illness and syptoms lasted for more than 6 months  and this is a major marker for CFS, or Chronic Fatigue Syndrome. Their research focused solely on the people who developed CFS after having had the pathogen, infectious mononucleosis , IM -glandular fever mainly Epstein Barr virus EBV (. As our members know shingles, chickenpox also known as human herpesvirus 6 is also known to result in CFS, as are the following viruses, Q fever, Ross River virus (Australian mainly), enterovirus (15) , and parovirus B 19.)

However the focus of their very thorough research was mononucleosis ;  they did a  study with 301 mono patients using the 21st century approved test markers for mono patients . The study came about because they wanted to compare their findings to those of of Bachweld and colleagues, who in 2000 found that 12% of subjects had not recovered from mono and were reporting CFS and impaired function 6 months following the mono. 76%of those who did not recover were female. Nearly identical results were reported by Australian researchers where 11 and 9 % of the subjects had CFS at 6 and 12 months following onset of mono, Q fever, and Ross River fever.

Broderick and his fellow researchers used 301 adolescents from Chicago who were diagnosed with acute mono. 6 months after clinical evaluation of mono, 39 of the 53 still ill had not full recovered and were diagnosed with CFS. 35 of the 39 subjects with CFS were female. Race and socioeconomic status had no affect on the subjects, neither did family or age. Plasma samples were available from 13  CFS patients 24 months after the diagnosis of mono, and from 12 recovered controls, matched as closely as possible to the subject CFS group, by gender, age, and Tanner testing stage (4-5).

It is the plasma testing for bio markers which is of most interest to CFS patients. The plasma markers for CFS induced by mono may or may not show up when CFS patients who contracted CFS after contracting one of the other viruses listed in the introduction to this report. If we can identify markers we can begin to learn to find a way to treat the neuro-endocrine immune disease of CFS. WE hope this will be true, and that Broderick and his research team will lead the way for future research to be done.  Broderick and his team were rigorous; each plasma sample was run in duplicate and rigorous scientific protocol was followed. See his article for the details.

Broderick, and his team discovered a unique plasma cytokine expression in CFS patients who became ill after having mono.  The plasma cytokines between CFS cases and recovered controls showed significantly different levels of  plasma IL -8 , IL- 23 and possibly IL-2 and Il -5. The most striking difference in plasma cytokine expression was in IL-23 ; the median concentration of this cytokine was significantly lower in patients with CFS than in recovered controls. This adolescent group of CFS patient results matched those of adult subjects with an unknown etiology, or cause of CFS, since their IL-23 cytokine plasma expression was abnormally low too.

Broderick and his team found that it was necessary to use 5 cytokines in the  plasma samples to separate the CFS patients from the recovered controls. Il 2, IL 5, IL 6,  IL 8, and IL 23 were selected  and research strongly suggests that the TH 17 immune response , causes the illness- specific differences in the body's immune responses, and this  atypical immune response may affect a significant subset of CFS patients.

The reason Broderick and his team have created excitement is because they are looking at the immune system and identifying CFS as a neuro-endocrine immune disease. Hormones act as immunomodulators, altering the sensitivity of our immune system. Vitamin D also regulates our immune system, since a T-cell extends a vitamin D receptor when it encounters a foreign pathogen in our body. T-cells guard us and have a symbiotic relationship with vitamin D. It is conjectured that a progressive decline in hormone levels with age weakens the immune response, as does  the dropping vitamin D levels. Sleep deprevation also weakens the immune system, and our immune response to our viral infection may result in changes to our sleep cycle , including increasing slow-wave sleep, relative to REM sleep.

Cytokines send signals to our cells; they modulate our imune agents, like interleukins and interferons. Concentrations can increase up to 1000 times during trauma or infections. The immune system remains a mystery and its function, and division into immune and hormonal responses remains the next great frontier of medical research. It can't happen fast enough for those of us with CFS.

The plasma Interleukin 5 or IL-5, stimulates cell growth and increases immunoglobulin secretion. It has long been associated with the cause of several allergic diseases including allergic rhinitis and asthma, airway tissue and induced sputum have been observed. It has a role in the elimination of antibody bound parasites.

The plasma Interleukin 8 or IL-8 mediates our immune response; if it is high we are having an immune reaction to some pathogen in the body. (virus etc. )

The plasma Interlukin-23 subunit alpha is a protein and stimulates the production of interferon-gamma to support our immune system. It is an important part of the inflammatory response against infection. In tandem with IL-6 and TGF-B1, IL-23 stimulates naive CD4+T cells to change into cells called Th17 cells , a proinflammatory cytokine that enhances the immune T-cell priming and stinulates the production of proinflammatory molecutes, and chemokines resulting in inflammation.
*** Note- mice deficient in either subunit of IL-23 receptor develop less severe symptoms of MS and inflammatory bowel disease, highlighting the importance of IL-23 in the inflammatory pathway.

I hope that the information which I gleaned from researching Broderickès research will give you and yours pause for thought. My doctor has always known that I have what he terms an UNUSUAL immune system. Now perhaps we have more clues to why my body reacts to pharmaceuticals in unusual reponse  modes. We have clues but now we need to hope for treatments to regulate our immune system for us. Vitamin D has been a treatment protocol for my doctor and now I know that he is on the right track.


Biomakers in CFS - wikipedia

Immune System - wikipedia

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue(2012)
Gordon Broderick, Ben Z Katz, Henrique Fernandes, Mary Ann Fletcher, Nancy Klimas, Frederick A Smith,
Maurice RG O’Gorman, Suzanne D Vernon6 and Renee Taylor

Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome(2010)
Mary A Fletcher, Martin Rosenthal, Michael Antoni, Gail Ironson, Xiao R Zeng, Zachary Barnes,
Jeanna M Harvey, Barry Hurwitz, Silvina Levis, Gordon Broderick, Nancy G Klimas

Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia(2009)
Toru Nakamura, Stephan K. Schwander, Robert Donnelly, Felix Ortega, Fumiharu Togo,
Gordon Broderick, Yoshiharu Yamamoto, Neil S. Cherniack,
David Rapoport, and Benjamin H. Natelson

Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood(2008)
Anne L Aspler, Carly Bolshin, Suzanne D Vernon and Gordon Broderick