Volgens een studie van Prof. de Meirleir,
Vince Lombardi en anderen
kan men met zeer grote nauwkeurigheid (specificiteit en sensitiviteit)
CVS-patiŽnten van de rest onderscheiden op basis van vier immunologische markers:
interleukine-8 (een cytokine),
de oplosbare vorm van CD14, een marker voor LPS (endotoxinen),
prostaglandine E2, een marker voor inflammatie, en (een afname van) het aantal CD57+ NK cellen.
A panel of biomarkers accurately identifies CFS/ME patients and
contributes to the understanding of the pathophysiology of the disorder.
IACFS/ME Conference, 2016 October 27-30. Fort Lauderdale, Florida: 30.
Kenny L. De Meirleir 1,2, Tatjana Mijatovic 3, Eugene Bosmans 3,
Nossa Van den Vonder 2, Vincent Lombardi 1
1. Nevada Center for Biomedical Research at University of Nevada, Reno, USA
2. Himmunitas vzw, Brussels, Belgium
3. RED Laboratories NV, Zellik, Belgium
CFS/ME is a debilitating illness for which no specific biomarkers have been identified,
although several immune abnormalities including neuroinflammation have been described.
The goal of this study was
to assemble a panel of immune and inflammatory markers,
with the ability to accurately identify CFS/ME cases.
From observations made in clinical practice, four markers were selected (immune and inflammatory).
These markers were initially investigated
to establish differences between CFS/ME cases and controls.
We then evaluated their potential usefulness as a diagnostic biomarker
by establishing their specificity and sensitivity.
Venous blood was collected from 70 male and 70 female CFS/ME patients
(mean age 43 and 44 years, respectively - Fukuda case definition was used)
as well as 70 male and 70 female healthy controls (mean age 43.5 and 44.5 years, respectively).
Serum Interleukin 8 (IL-8),
soluble CD14 (sCD14, a surrogate marker for bacterial LPS), and
prostaglandin E2 (PGE2) were measured for all subjects as were absolute
CD3- / CD57+ lymphocytes counts (CD57+ lymph),
according to accepted clinical laboratory techniques.
We then established median values for all analysed parameters;
independent sample t-test, Mann-Whitney test and ROC curve analysis
were used to investigate difference linked to gender and age.
ROC Statistics (area under the ROC curve) revealed
a significant difference
between CFS/ME cases and controls (p < 0.001) for the four parameters separately,
both in the male and female cohorts.
Sensitivity was 74.3 - 80 % (females) and 52.1 - 85.9 % (males).
Specificity was 57.1 - 98.1 (females) and 65.7 - 88.6 (males).
Logistic regression analysis for
the combination of parameters in our panel (IL-8, sCD14, PGE2 and CD57+ lymph)
correctly predicted in 89.36 % of male CFS/ME cases and in 97.14 % of female CFS/ME cases.
This panel differentiates CFS/ME cases from controls
with high sensitivity and specificity and
therefore represents a potential tool in selecting CFS/ME subjects for clinical studies.
Each of these four biological markers relate strongly to the disorder.
PGE2 activates dendritic cells and suppresses their ability to attract T cells.
It also suppresses the function of macrophages and neutrophils as well as
Th1, CTL-, NK-cell mediated type 1 immunity (e.g. CD3- / CD57+ lymphocytes).
PGE2 additionally promotes Th2, Th17 and Tregs and also modulates chemokine production (e.g. IL-8).
When taken together, these data suggest that lipopolysaccharide (LPS),
likely from gut bacteria, plays an important role in the pathophysiology of CFS/ME.
This screening panel represents an initial step toward identifying biomarkers
to broadly diagnose subjects with CFS/ME.
Subsequent markers will be required to subcategorize CFS/ME subjects
in order to tailor therapeutic solutions.