Evidence of Inflammatory Immune Signaling in Chronic Fatigue Syndrome:

A Pilot Study of Gene Expression in Peripheral Blood

Anne L Aspler, Carly Bolshin, Suzanne D Vernon and Gordon Broderick

Behavioral and Brain Functions 2008, 4:44doi:10.1186/1744-9081-4-44

Published:

26 September 2008

Abstract (provisional)

Background

Genomic profiling of peripheral blood reveals altered immunity in

chronic fatigue syndrome (CFS) however interpretation remains

challenging without immune demographic context. The object of this work

is to identify modulation of specific immune functional components and

restruct uring of co-expression networks characteristic of CFS using

the quantitative genomics of peripheral blood.

Methods

Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells,

CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published

data. A group of 111 women were classified using empiric case definition

(U.S. Centers for Disease Control and Prevention) and unsupervised

latent cluster analysis (LCA). Microarray profiles of peripheral blood

were analyzed for expression of leukocyte-specific gene sets and

characteristic changes in co-expression identified from topological

evaluation of  linear correlation networks.

Results

Median expression for a set of 6 genes preferentially up-regulated in

CD19+ B cells was significantly lower in CFS (p=0.01) due mainly to

PTPRK and TSPAN3 expression. Although no other gene set was

differentially expressed at p<0.05, patterns of co-expression in each

group differed markedly. Significant co-expression of CD14+ monocyte

with CD16+ neutrophil (p=0.01) and CD19+ B cell sets (p=0.00)

characterized CFS and fatigue phenotype groups. Also in CFS was a

significant negative correlation between CD8+ and both CD19+

up-regulated (p=0.02) and NK gene sets (p= 0.08). These patterns were

absent in controls.< /DIV> < DIV class= ygrp-content>

Conclusions

Dissection of blood microarray profiles points to B cell dysfunction

with coordinated immune activation supporting persistent inflammation

and antibody-mediated NK cell modulation of T cell activity. This has

clinical implications as the CD19+ genes identified could provide

robust and biologically meaningful basis for the early detection and

unambiguous phenotyping of CFS.

The complete article is available as a provisional PDF. The fully

formatted PDF and HTML versions are in production.

Abstract:

http://www.behavioralandbrainfunctions.com/content/4/1/44/abstract

Provisional PDF:

http://www.behavioralandbrainfunctions.com/content/pdf/1744-9081-4-44.pdf