Latest paper from Lights doesn't really clarify things
I think that, along with XMRV and Rituximab, the 2011 report of increased gene expression in response to exercise (that Cort's written about here) is amongst the most interesting findings to emerge about CFS. However, as with XMRV and Rituximab, replication is crucial.
The biggest concern over the study covered in Cort's article relates to the higher exertion levels of CFS patients than controls, as has been discussed elsewhere in the comments. The authors had indicated that submitted research would demonstrate that in response to exercise MS patients showed no change in the expression of the genes that increased post-exercise in CFS patients. This would go some way to demonstrate the changes were unique to CFS and not related to deconditioning, particularly if the MS patients were well-matched with the CFS ones in terms of activity levels.
We have shown in a recently submitted manuscript that these gene markers are not similarly increased in patients with MS who exhibit unexplained increases in fatigue (White, A.T., Light A.R., Hughen R.W., VanHaitsma T.A., and Light K.C. Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in multiple sclerosis, chronic fatigue syndrome, and healthy controls, submitted).
This submitted
paper on MS patients has now been published and while it shows that metabolite receptor gene expression is not increased in response to gene expression, it also shows that the adrenergic recepotor genes
are similarly increased in MS and CFS patients. Which makes it far less conclusive. It's not clear how well matched the MS patients were to the CFS patients.
This further study (from a comment from Alan posted by Cort) looks interesting re deconditioning, but like the MS study, we won't know for sure until it's published.
We also have a study in progress that looks at normal subjects at three different levels of exercise. A VO2 max test,a full cycling time trial, and a full cycling time trial with their core temperature increased by 2 degrees C. So far, with these max tests, most ofthe sensory genes actually go down in these normal subjects. AD2A does go up,but not as much as in patients, and Beta 2 actually goes down in all but the VO2 max test.
What I found of most concern was that the moderate-to-strong link found between gene expression and fatgiue and pain scores across all the genes implicated in this (2011) paper was not replicated in the new MS/CFS paper. The only correlation found was for a single adrenergic gene, P2X4, and then only for pain and not for fatigue. It was this correlation between gene expression and fatigue and pain that made the findings of this 2011 paper so compelling.
Replication studies have not been kind to the XMRV findings to date, though the largest and most rigorous (Lipkin) study has yet to report. Replication of the Rituximab findings are planned by its authors and at least one other group. The authors of these gene expression findings
have made it clear they believe their work to date is sufficient:
We believe the published studies we have provided are sufficient to demonstrate that at least some genes that are involved in fatigue detection [and immune cell modulation] are dysregulated in CFS, and that this may contribute to some of their symptoms.
As the CAA, who funded this study say "As with any research, these findings will need to be replicated by another research group in another group of CFS (and FM) patients", to establish that these gene expression are a real and important link to fatigue and pain in CFS. Hopefully other groups will do exactly this.
