05 October 2008
Evidence of Inflammatory Immune Signaling in Chronic Fatigue
Syndrome: A Pilot Study of Gene Expression in Peripheral Blood.
Journal: Behav Brain Funct. 2008 Sep 26;4(1):44. [Epub ahead of print]
Authors: Aspler AL, Bolshin C, Vernon SD, Broderick G.
NLM Citation: PMID: 18822143
ABSTRACT:
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 restructuring 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.
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.