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De Meirleir:

combinatie van

vier immunologische biomarkers

onderscheidt patiŽnten van anderen








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.