Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26

• Published in: PloS one Vol. 5; no. 5; p. e10817
• Main Authors: Fletcher, Mary A, Zeng, Xiao R, Maher, Kevin, Levis, Silvina, Hurwitz, Barry, Antoni, Michael, Broderick, Gordon, Klimas, Nancy G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.05.2010; Public Library of Science (PLoS)
• Subjects: Abnormalities; Adolescent; Adult; Age; Alcohol; Analysis; Antigens; Assaying; Bioassays; Bioindicators; Biological markers; Biomarkers; Biomarkers - blood; Cadmium; Case-Control Studies; Cell activation; Chromium radioisotopes; Chronic fatigue syndrome; Chronic illnesses; Cytokines; Cytometry; Cytotoxicity; Cytotoxicity, Immunologic; Diabetes; Diagnostic systems; Dipeptidyl Peptidase 4 - blood; Dipeptidyl-peptidase IV; Drug abuse; Enzyme-linked immunosorbent assay; Fatigue; Fatigue Syndrome, Chronic - blood; Fatigue Syndrome, Chronic - diagnosis; Fatigue Syndrome, Chronic - enzymology; Fatigue Syndrome, Chronic - immunology; Female; Flow cytometry; Health aspects; Hepatitis; Humans; Immunoglobulins; Immunology; Immunology/Immunity to Infections; Immunology/Innate Immunity; Immunology/Leukocyte Activation; Infectious Diseases/Viral Infections; Inflammation; Insulin resistance; Killer cells; Killer Cells, Natural - immunology; Laboratory tests; Lymphocytes; Lymphocytes T; Male; Measurement methods; Medical research; Medicine; Middle Aged; Natural killer cells; Peptidase; Prognosis; Rheumatoid arthritis; ROC Curve; Studies; Systematic review; T cells; Toxicity; Women's Health; Young Adult; Florida; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010817

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 (51)Cr 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.