Nice to have PR back online.
Papers on immune functioning are not easy to understand largely because the immune system itself is so vast and complex. The terminology can be baffling (FoxP3 & VPACR2, anyone?) Anyway, I'm generally baffled, but I've tried to make some sense of this paper.
Problem with the CFS cohort
Unfortunately, the CFS sample, though large (n=95), is a bit flaky which compromises the results. They used the
International/Ambiguities definition, which fine (basically just an updated Fukuda; Klimas and Jason are among the authors). But crucially Brenu et al failed to do a clinical evaluation as required. Instead they used a self-report questionnaire and patient records. Using these methods, 20% of the self-reported cases were deemed not to be CFS and it's likely quite a few more would have been excluded had they used a proper clinical evaluation. This failing inevitably casts some doubts over the findings.
It's also worth noting that although Nancy Klimas is a co-author she merely critically reviewd the paper and was not involved in design, execution or analysis of the study itself.
Key finding: further confirmation of Natural Killer Cell reduced Cytotoxicity
For me the most important thing to come out of this paper was futher confirmation that the ability of Natural Killer cells to kill is reduced in CFS patients. The difference is large - NK cells kill 28% of target cells in controls but only 15% of target cells were killed in the CFS group (p<0.05) so it is very likely to be valid even allowing for the compromised selection of CFS patients. These figures are very similar to the Klimas findings last year (healthy controls 28% kill rate, CFS 12%, p<0.0005), but come from a different research group looking at different patients.
More uncertainty in other immune findings
As the authors say
Studies have identified abnormalities in immune function but these data are inconsistent
Apart from the NK findings above, this pattern of inconsistency continues.
This study looked at some cytokines and found that both IFN-gamma and TNF-alpha were significantly increased in CFS patients. There have been inconsistent findings on this in the past and this is the largest study to have found increases, which is why it's such a shame they didn't nail down firm diagnoses for their CFS patients.
They also looked in more detail at NK cell cytotoxicity. NK cells kill by injecting a cocktail of molecules into the victim cell, including Grazymes that chew up cell contents and Perforin that perforates the cell by forming pores in the membrane. Previous studies had shown reduced levels of these 2 molecules in CFS patients' NK cells, perhaps explaining why they were poor at killing. The Brenu study looked at gene expression of Granzyme and Perforin (rather than levels of the proteins themselves) and found that while Granzyme expression was decreased, Perforin levels were surprisingly increased. So, more confusion all round.
New findings.
The study also investigated several meausres of immune function that haven't previously been investigated in CFS patients and found various differences between patients and controls (eg FoxP3 and NK CD56bright expression) though whether or not these differences are significant or will be replicated by other researchers remains to be seen.
