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A panel of biomarkers accurately identifies CFS/ME patients and contributes to the understanding of the pathophysiology of the disorder

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By Kenny L. De Meirleir et al.

Abstract 

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Source: Kenny L. De Meirleir1,2, Tatjana Mijatovic3, Eugene Bosmans3, Nossa Van den Vonder2, Vincent Lombardi1. A panel of biomarkers accurately identifies CFS/ME patients and contributes to the understanding of the pathophysiology of the disorder. Abstract from IACFS/ME Conference 2016 Program.

1. Nevada Center for Biomedical Research at University
of Nevada, Reno, USA
2. Himmunitas vzw, Brussels, Belgium
3. RED Laboratories NV, Zellik, Belgium

 

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