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Nancy Klimas, May 2010: Biomarkers in Chronic Fatigue Syndrome


Patient in training

Chronic Fatigue Syndrome (CFS) studies from our laboratory and others described decreased natural killer cell cytotoxicity (NKCC) and elevated proportion of lymphocytes expressing the activation marker, dipeptidyl peptidase IV (DPPIV) also known as CD26. However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS.

Subjects included female and male CFS cases and healthy controls. NK cell function was measured with a bioassay, using K562 cells and 51Cr release. Lymphocyte associated DPPIV/CD26 was assayed by qualitative and quantitative flow cytometry. Serum DPPIV/CD26 was measured by ELISA. Analysis by receiver operating characteristic (ROC) curve assessed biomarker potential. Cytotoxic function of NK cells for 176 CFS subjects was significantly lower than in the 230 controls. According to ROC analysis, NKCC was a good predictor of CFS status. There was no significant difference in NK cell counts between cases and controls. Percent CD2+ lymphocytes (T cells and NK cells) positive for DPPIV/C26 was elevated in CFS cases, but there was a decrease in the number of molecules (rMol) of DPPIV/C26 expressed on T cells and NK cells and a decrease in the soluble form of the enzyme in serum. Analyses by ROC curves indicated that all three measurements of DPPIV/CD26 demonstrated potential as biomarkers for CFS. None of the DPPIV/C26 assays were significantly correlated with NKCC.

By ROC analysis, NKCC and three methods of measuring DPPIV/C26 examined in this study had potential as biomarkers for CFS. Of these, NKCC, %CD2+CD26+ lymphocytes and rMol CD26/CD2+ lymphocyte, required flow cytometry, fresh blood and access to a high complexity laboratory. Soluble DPPIV/C26 in serum is done with a standard ELISA assay, or with other soluble factors in a multiplex type of ELISA. Dipeptidyl peptidase IV on lymphocytes or in serum was not predictive of NKCC suggesting that these should be considered as non-redundant biomarkers. Abnormalities in DPPIV/CD26 and in NK cell function have particular relevance to the possible role of infection in the initiation and/or the persistence of CFS.



By ROC analysis, NKCC and three methods of measuring DPPIV/C26 examined in this study had potential as biomarkers for CFS.

4 potential bio-markers|!!??!! Pinch me. I must be dreaming.


The game is afoot
The closing slide of Nancy Klimas' presentation at the IiME conference listed the following biomarkers for, and mediators in, ME. Please do not ask me to explain them.

NK cells
Perforin as a surrogate for NK cells, also measures cytotoxic T cell function
Soluble CD26
NPY (and directly impacted by CD26)
Cytokine multiplex methods
Panels pointing to pro-inflammatory cytokine elevations, TH2 cytokine elevations, etc.
Micro-array work

I have more notes but it will take a while to compile them.


OK, so this is awesome, and Nancy one of my favorite super sexy fierce heroes, but...what now?

She had a small study of 176 patients and 230 controls. It was funded by the CAA, NIAA (National Institute on Alcohol Abuse and Alcoholism), NHLBI (National Heart, Lung and Blood Institute), and NIAID. She's following up with a longitudinal study with about the same # of people.

It was be my life's dream and frankly tear inducing if one could walk into a PCP office, get some blood requisition, and get a diagnosis. No schlepping around to specialist, no one accusing patients of depression or failing at life.

For something to be a standard test it has to be 1) replicated 2) repeated and found true on a HUGE number of people and not in controls and then FDA approved, insurance-covered, and hopefully put in the Merck Manual, etc. (And sanctiond by the NYSDOH which apparently doesn't allow NCK function testing.)

What can we do to help this happen?


ahimsa_pdx on twitter
What can we do to help this happen?

I'm with you, Robin. I keep seeing studies come out but no one doing the follow-up to make a diagnostic test that is "FDA approved, insurance-covered, and hopefully put in the Merck Manual, etc."

I have no idea what patients can do to push the work needed to create a standardized diagnostic test but I agree with you that it is sorely needed.


iherb 10% discount code OPA989,
australia (brisbane)
Hi, Im currently in a cfs study here in australia, they are studying the function of natural killer cells, not just numbers, anyway after the first round of blood tests they have found cfs pts compared to the healthy controls have poor natural killer cell function, so another study validating our problems with our immune system. They also said that because of this that we can then be prone to other infections. I was once told by a docotor that ebv reactivation only occurrs in aids and cancer patients going through chemo, these sort of studies are proving that cfs patients could have ebv reactivation as well as other infections that are thought of as benign such as mycoplasma etc


Senior Member
Heapsreal~ Is anything published yet in the study that you are participating in?
Best, Timaca


Senior Member
Rock on: another paper to put in the hands of uninformed and/or incurious docs.


iherb 10% discount code OPA989,
australia (brisbane)
hi timaca, nothing yet, the study is over an 18month period with blood tests done every 6 months, so i assume at the end of the 18month period, so another 12 months to go.