Pilot assessment of low NK cell-mediated ADCC and FCGR3A genetics in(ME/CFS):.. low ADCC unsuitable as diagnostic biomarker: Sung, Bateman et al 2019

Pilot assessment of low NK cell-mediated ADCC and FCGR3A genetics in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Based on inclusion of family members without ME/CFS as controls, low ADCC is unsuitable as a diagnostic biomarker

Alexander P. Sung, Jennifer J-J Tang, Michael J Guglielmo, Julie Smith-Gagen, Lucinda Bateman, Doug D. Redelman, Dorothy Hudig

Preprint, not peer reviewed.

https://www.medrxiv.org/content/10.1101/2019.12.20.19015438v1

 

Disappointing of course that their hunch for a biomarker didn't work out but refreshing to see them state their null result so clearly. Too many others would have tried to dress it up as something it isn't. Ruling things out is valuable; we can move our scarce resources on to the next line of enquiry.

Much of the paper is too technical for me but I found the inclusion of healthy family members as controls interesting. I wonder why it's not being done more often? It seems a worthwhile thing to do.

Basically they found significant differences in ADCC between patients and healthy (unrelated) controls which would normally create a great deal of excitement. But when they looked at the healthy family relatives, their ADCC levels were much the same as the patients', so ADCC couldn't distinguish between healthy and ill family members which makes it useless as a biomarker (though it still could still mark a predisposition for ME).

 

I have not looked at the stud details thoroughly but I wonder if there may be some selection bias in the finding of a difference between ME families and controls. These are families with multiple ME cases - which are not a representative sample of ME per se. The Fc receptor polymorphisms may have been detected earlier and the associated shift in NK function assay results may not be entirely prospective.

I agree, however, that the comparison with family members is useful in showing that it is not the ME that causes the poor NK function results.