2008 - Evidence of inflammatory immune signaling in CFS: gene expression in peripheral blood

[Bob]

Open access.

This isn't new but I can't find a dedicated discussion about it on the forum, so I thought I'd post it. It's a paper from 2008 that explores abnormalities in gene expression in immune cells including B cells. (Note that it uses the empirical definition - so it may be a heterogeneous cohort of people who experience fatigue.)

I've only just come across it so I haven't yet read the full paper, but the abstract is eye-catching, especially the conclusion.


Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood.
Aspler AL, Bolshin C, Vernon SD, Broderick G.
2008 Sep 26.
Behav Brain Funct. 4:44.
doi: 10.1186/1744-9081-4-44.
http://www.ncbi.nlm.nih.gov/pubmed/18822143

Full paper:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569951/
http://www.behavioralandbrainfunctions.com/content/4/1/44

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.

CONCLUSION:
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.

 

[Bob]

@Jonathan Edwards, perhaps you might be interested in this paper, if you haven't already seen it? It also includes a range of interesting references relating to research of immune-cells in ME patients.

 

[Jonathan Edwards]

@Jonathan Edwards, perhaps you might be interested in this paper, if you haven't already seen it? It also includes a range of interesting references relating to research of immune-cells in ME patients.

Thanks Bob,
I am not overimpressed by what is in the abstract but will try to look at the full paper. A difficulty with looking at gene expression in circulating B cells is that you are grouping together cells at very different stages of maturation and differentiation. A slight shift in trafficking will alter proportions of cells with quite different activities.

 

[Marco]

Thanks Bob,
I am not overimpressed by what is in the abstract but will try to look at the full paper. A difficulty with looking at gene expression in circulating B cells is that you are grouping together cells at very different stages of maturation and differentiation. A slight shift in trafficking will alter proportions of cells with quite different activities.

Fair point - if you're comparing one individual to another but with sample sizes of approx 70 'fatigue patients' and 35 controls - wouldn't the 'slight shift in trafficking' even out? (just a technical question - I'm not convinced there's anything meaningful here).

 

[anciendaze]

There is a fundamental problem here because this cohort was put together using the Reeves "empirical" definition. It could well be dominated by patients with major depressive disorders.

I do think there is evidence of inflammatory processes both in many cases of depression and in ME/CFS. What would be very interesting would be to test for levels of PEPITEM or active genes producing it, to see if there was a defect in the signalling to limit recruitment of cytotoxic T-cells to endothelial tissues. Inflammation in capillaries by such a runaway process would be essentially invisible in ordinary clinical examination.

Unfortunately, this research didn't take place at a time when PEPITEM signalling was known.

 

[Jonathan Edwards]

Fair point - if you're comparing one individual to another but with sample sizes of approx 70 'fatigue patients' and 35 controls - wouldn't the 'slight shift in trafficking' even out? (just a technical question - I'm not convinced there's anything meaningful here).

I agree that if the statistics are good there would still seem to be a difference of some sort. My worry is that it is interpreted as a difference in function of a cell type when it may simply be a shift in trafficking. Both might be interesting but the interpretation in terms of an inflammatory process or whatever might be premature. When we study B cells we essentially do not bother to look at the whole CD19 population because it is too heterogeneous and any changes are impossible to interpret. I tend to worry when people talk of shifts in gene expression without breaking it down into specific cell types.