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.
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
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.
Citation: Fletcher MA, Zeng XR, Maher K, Levis S, Hurwitz B, et al.
(2010) Biomarkers in Chronic Fatigue Syndrome: Evaluation of Natural
Killer Cell Function and Dipeptidyl Peptidase IV/CD26. PLoS ONE 5(5):
Editor: Derya Unutmaz, New York University, United States of America
Received: April 9, 2010; Accepted: May 2, 2010; Published: May 25, 2010
Copyright: © 2010 Fletcher et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original author and source
Funding: This work was supported by grants from the NIAAA: R21AA016635
(PI MA Fletcher); NIAID: R01AI065723 (PI MA Fletcher); CFIDS Assoc. of
America: (PI N Klimas); NIAID: UO1 AI459940 (PI N Klimas), NHLBI: RO1
HL65668 (PI B Hurwitz); NIAMD: R01 AR48932-01A1 (PI S Levis). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing
* E-mail: [email protected]
# These authors contributed equally to this work.