An evaluation of biochemical markers in Chronic Fatigue Syndrome – research paper published online on 25 May 2010

From PloS One, open access journal, 26 May 2010 (Dr Klimas mentioned at the Invest in ME Conference in London on 25 May that the paper was about to be published).

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

Mary A. Fletcher1,2,3#*, Xiao R. Zeng1,2, Kevin Maher1, Silvina Levis1,2, Barry Hurwitz3, Michael Antoni3, Gordon Broderick4, Nancy G. Klimas1,2,3#

1 Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America, 2 Miami Veterans Health Care Center, Miami, Florida, United States of America, 3 Department of Psychology, University of Miami, Coral Gables, Florida, United States of America, 4 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Abstract

Background

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.

Methods/Results

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.

To read the full paper, click here.

 

 

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