In een recente studie tonen Klimas, Broderick en kollega's wederom aan dat
immunologische afwijkingen een hoofdrol spelen in ME/CVS.
De studie bevestigt dat de NK cellen ("massavernietingsingswapens") niet goed functioneren.
Ook toonden de onderzoekers aan dat relatief veel T- en NK-cellen geaktiveerd zijn (de CD26-"signaalvlag" hijsen),
alhoewel dit niet helemaal goed gebeurt ("zwak signaal").
De twee markers (CD26-aktivatiemarker en
NK-cel aktiviteit) zijn volgens de auteurs
twee onafhankelijke biomarkers voor ME/CVS met grote sensitiviteit en specificiteit.
Citaten uit het studierapport:
There is a considerable literature describing immune dysfunction in CFS [14]-[16],
although reviews of the immunology of CFS noted that universal agreement of immunological abnormalities had not been achieved,
in no small part due to differences in methodologies, case definition and study quality [17], [18].
However, redundant reports support
- reduced function of natural killer (NK) cells [14], [19] with deficiencies of perforin and granzymes in both NK cells and CD8 T cells [20];
- inflammation [21], [22];
- altered cytokine profiles [9], [10] with elevation of proinflammatory cytokines [11], [12] and Th2 (T helper cell type 2) polarization [11], [13]; and
- chronic lymphocyte activation [14], [16].
...
DPPIV/CD26 has a key role in immune regulation as a T cell activation molecule and in immune-mediated disorders ...
...
The data obtained on NK cell function, immune activation and DPPIV/C26 on cell surfaces and in serum, are consistent with a viral etiology for CFS.
Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26
PLoS ONE. 2010: 5(5): e10817. doi:10.1371/journal.pone.0010817
Fletcher MA, Zeng XR, Maher K, Levis S, Hurwitz B, Antoni M, Broderick G, Klimas NG.
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/CD26 assays were significantly correlated with NKCC.
Conclusions
By ROC analysis,
NKCC and three methods of measuring DPPIV/CD26
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/CD26 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.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010817
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