Biomarkers in Chronic Fatigue Syndrome: Evaluation of Natural Killer Cell Function and Dipeptidyl Peptidase IV/CD26

Abstract

BackgroundChronic 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.Methods/ResultsSubjects 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.ConclusionsBy 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.

Increased nuclear factor-κB and loss of p53 are key mechanisms in Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS)

“…The World Health Organization considers ME to be a nervous system disease. ME/CFS is an acquired neuro-immune disease [4,8,9] involving malfunctioning of the central nervous (CNS) [10][11][12] and immune system [4,[13][14][15][16]; pathologically dysfunctional impairments in cellular energy metabolism and ion transport mechanisms [17][18][19]; and abnormalities of the autonomic nervous and cardiovascular system [20][21][22]. Other findings indicate that ME may share basic immune pathophysiology with CFS but with additional PEM and significantly more immune disorders [4].…”

Are fatigue symptoms and chronic fatigue syndrome following Q fever infection related to psychosocial variables?

“…Some authors assume that a dysregulation of cytokines (increased IL-6 release, e.g. [7]) or impaired immune functions in general might be associated with CFS [16][17][18], while others think that the persistence of C. burnetii organisms (antigenic non-viable cell residues) in the host's bone-marrow [19,20], changes of immunogenetics [21,22], or concurrent cardiovascular problems might account for post Q fever fatigue.…”

Mini-Review Article – Current Opinion on Salivary Biomarkers as a Measurement for Stress and Fatigue

“…For instance, IL-6 is shown to be at higher levels in fatigued breast cancer survivors as compared to non-fatigued survivors [4]. Besides, CD26, a receptor on immune cells, is a good indicator of the function of natural-killer cells, and has been used to aid diagnosis of chronic fatigue syndrome or fibromyalgia [5]. However, these tests are invasive and cause discomfort to the subjects, and require trained healthcare professionals to collect blood specimens.…”