Study Confirms Decreases in Immune Function in CFS/ME Patients, Suggests Biomarker
via ProHealth.com • February 21, 2013
Editor’s Note: Natural killer (NK) cells are part of our body’s innate immune system. Their primary function is to reject tumor and virus infected cells. They do this by releasing granzyme and perforin, which are small protein granules that target cells to be destroyed. This process is called apoptosis or programmed cell death.
Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis
~Source: J Transl Med. 2012; 10: 88
By Ekua W. Brenu et al.
Background: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time. This study investigates Natural Killer (NK) cell cytotoxic activity, NK cell subsets (CD56 bright CD16- and CD56 dim CD16+) and cytokines, over the course of a 12-month period in patients with CFS/ME.
Methods: The participants in the study comprised 65 (47.2 ± 11.5 years) CFS/ME participants and 21 (45.2 ±9.3 years) non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1), 6 (T2) and 12 months (T3). Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells.
Results: NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56 bright CD16- NK cells at both T1 and T2. Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-gamma and TNF-alpha at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non-fatigued controls. Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56 bright CD16- NK cells were much lower at T2 compared to T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to T1 and T3.
Conclusion: These results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study
Source: J Transl Med. 2012; 10: 88 doi: 10.1186/1479-5876-10-88. Ekua W Brenu, Mieke L van Driel, Donald R Staines, Kevin J Ashton, Sharni L Hardcastle, James Keane, Lotti Tajouri, Daniel Peterson, Sandra B Ramos, and Sonya M Marshall-Gradisnik.
At the IACFS/ME Biennial Conference in September and again during an October 27 conference call, Hemispherx Biopharma, Inc. presented new research data on a diagnostic blood test for chronic fatigue syndrome (ME/CFS) that they have developed with Chronix Biomedical, Inc.
The aim of the research was to find signature DNA sequences from patients with ME/CFS compared to healthy controls with respect to their diagnostic predictive value. The Chronix technology used for the study is able to analyze DNA released into the bloodstream by dying and damaged cells and has the potential to detect genomic alterations unique to diseased cells.
DNA extracted from serum samples of ME/CFS patients and normal healthy controls was sequenced and compared to the human genome. A total of about 10,000 high-quality sequence reads were generated from each serum sample.
Four genes were identified that separated ME/CFS patients from the normal control group.
These results support additional studies done with a larger CFS cohort using more powerful sequencing techniques.
In addition to the obvious benefits of being able to accurately diagnose and evaluate ME/CFS patients, Hemispherx is hoping this blood test will also help them identify the ME/CFS patients that will respond best to their experimental drug Ampligen®, for which they are seeking FDA approval.
The possibility of a blood test that could aid in the diagnosis and treatment of ME/CFS is terribly exciting. And the idea that Hemispherx wants to use this test to find the ME/CFS patients who would be most likely to have a positive response to Ampligen makes me think that it may have the potential to differentiate between possible subsets of ME/CFS.
Gene sequencing has been touted as the future of medicine since we entered the 21st century, but I think many of us are just now beginning to get a glimpse of its huge potential. Hopefully one day it can be used to get faster and more accurate diagnoses for ME/CFS, fibromyalgia and so many other chronic pain illnesses. Sources:
Hemispherx Biopharma Chronic Fatigue Syndrome Conference Call. October 27, 2011.
Hemispherx Biopharma, Inc. Press Release. September 26, 2011.
I used dr. K. deMeirleir's Protea Biopharma Neurotoxic Metabolite Test Kit which aims to detect the presence of abnormal metabolites in the urine. It is a simple DIY kit that costs £25-35. These metabolites are related to the production of hydrogen sulphide (H2S), which is present in the body in small amounts under normal conditions and has certain physiological roles. An excess can be very detrimental, causing neurotoxic symptoms like photo-sensitivity, overload phenomenon and other symptoms of ME/CFS. Over-production of H2S is related to gut dysbiosis - too many bad bugs and not enough beneficial ones. DeMeirleir has concluded that a large proportion of people with ME/CFS present with such dysbiosis.
ME/CFS: H2S test. My sample turned violet right away; this shot is 15 seconds into the test.
ME/CFS: H2S test. My sample after the required 3-minute wait period, now opaque and deep violet.
ME/CFS: H2S test. The reference range for the H2S test: the square on the right is negative; the square in the middle is mildly positive; the final, darkest square is a strong positive.
My sample demonstrates a strong positive for H2S. My Comprehensive Digestive and Stool Analysis showed no significant pathogens, though a high index of dysbiosis was present with 0% L. acidophilous (after 12 years of taking Natren, VSL#3, kefir and others), and low bifidus. I do not eat any sugars or grains.
My cousin with ME/CFS also took VSL#3 and kefir (among other things), yet seemed to find improvement in test results which translated to a great improvement in his ME/CFS.
Some very exciting news!
BELGIUM via the NATIONAL ME/FM ACTION NETWORK
Dr. Kenny De Meirleir of the Brussels Free University (VUB) has announced that he has successfully developed a diagnostic test for ME/CFS. The Myalgic Encephalopathy Association Belgium (MEAB) estimates there are between 30,000 to 40,000 people in Belgium with ME/CFS.
Since 2002, the Flemish government has invested over €10 million in five "reference centres" across the region in Leuven, Antwerp, Ghent and Brussels for the diagnosis and treatment for ME/CFS but offer only cognitive behavioural therapy and physical rehabilitation.
"These people have been mistreated for years," Dr De Meirleir says. "CFS was treated as a psychosomatic complaint. But someone who runs 10 metres after a bus and then has to spend a week in bed recovering has a serious medical problem."
The test, manufactured by Protea Biopharma, in which Dr De Meirleir is a partner, detects the presence of hydrogen sulphide (H2S), which is produced in the intestines when bacteria come in contact with heavy metals. People with ME/ CFS have been shown to have higher concentrations of intestinal bacteria than normal, which leads to higher levels of H2S.
H2S is a gas present in minuscule concentrations in normal people but at toxic levels in ME/CFS patients. The reasons for overproduction of bacteria can range from lactose intolerance to viral infection to stress.
According to the draft of a journal article soon to be published by Dr. De Meirleir and his team, H2S causes intolerance to light and noise, a depressed immune system and low white blood cell count. It also leads to retention of mercury by the body, which in turn produces cell death and damage to energy metabolism. The biggest effects, though, are produced on the central nervous system, explaining the main symptoms of ME/CFS.
“There’s still a great deal of work to be done to find a cure” Dr. De Meirleir told Radio 1 listeners "CFS is not an illness, it's a condition," which means that the underlying causes of ME/CFS could vary widely and that each would have to be treated on its own.
Note: Dr. Kenny De Meirleir was one of the panel members of the Canadian ME/CFS Working Case Clinical Definition, Diagnostic & Treatment Protocols, a Consensus Document published in 2003.