Jam tomorrow, and important general points
Promising areas but no firm results yet...
The importance of cell subtypes and subgroups
Unutmuz stressed the importance of looking in detail at different immune types and subtypes, particularly for T cells. Nath found mitochondrial deficits looking at white blood cells (i.e. blood immune cells) but said they now needed to look at results by cell type. Hanson said she had similar results to Nath and also stressed the importance of looking at different cell types.
An analogy for this problem is comparing a fruit smoothie with a bowl of fruit. A fruit smoothie gives you an average, 'bulk' fruit taste, much like looking at all white blood cells together. The bowl of fruit contains the individual cell types and looking at (tasting) these individually is likely to tell you far more about fruit. If the fruit smoothie has an 'off' taste, what is really going on?
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The ultimate approach is to study each individual cell separately, and that's happening here:
Detailed examination of gene expression by cell type (and beyond). Hanson was clearly excited by Dr Andrew Grimson's gene expression study using white blood cells. Previous studies looking at gene expression in all cells together have been inconclusive (the fruit smoothie approach).
@Hutan said Grimson was looking at 270,000 individual cells, which makes it sound to me like
single-cell RNA sequencing (scRNA-seq). This is much more expensive but gives the most detail and the most robust results. So far, Hanson said the researchers have established what is "normal" in gene expression following exercise. Next, they compare with ME/CFS.
Gene expression analysis can probe results by cell types (e.g. T cells, T-helper cells and Th subtypes: these can be identified by particular gene transcripts). It can also look in even greater detail, down to the level of the individual cell.
Inflammation in the brain? The long awaited brain PET study looking for microglia activation, by Dr Dikoma Shengu in Hanson's group, has been delayed by Covid. Microglia are the brain's immune cells and their activation (aka inflammation) was first seen in that small Japanese study in about 2015. (However, another equally small but slightly better done more recent study failed to replicate this.) Shengu's study is much bigger and looks both before, during and after exercise.
Metabolomics... Most of the results are still to come, including a 90 patients/90 controls cohort from Hanson's team, more from Unutmuz and Dr Oliver Fiehn in Lipkin's team. I am particularly interested in Fiehn's work because he is a metabolomics specialist, one of the tope ones in the US (he heads up the NIH's West Coast metabolomics lab).
At last, replication (sort of)
Finally, different groups are starting to look at the same problem, such as metabolomics, mitochondria and microbiome - giving the chance to gain real understanding rather than just producing shiny new findings that often don't go anywhere
. This isn't entirely an accident: the NIH, I believe, encouraged the different groups to take overlapping approaches.
