Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild MECFS, Bonilla et al, 2022

https://www.frontiersin.org/articles/10.3389/fimmu.2022.841910/full

Myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS) is a serious disease whose cause has yet to be identified. Objective markers of the disease are also not well understood and would serve as important tools in diagnosis and management. One potential biomarker or transmitter of immune signals in ME/CFS is the extracellular vesicle (EV) compartment. These small, membrane bound particles have been shown to play a key role in intercellular signaling. Our laboratory has focused on methods of detection of EVS in clinical samples. In this study we explored whether the prevalence of EVs in the plasma of participants with mild or severe ME/CFS differed from the plasma of healthy control participants. By staining for multiple cell surface molecules, plasma EVs could be fingerprinted as to their cell of origin. Our study revealed a significant correlation between severe ME/CSF and levels of EVs bearing the B cell marker CD19 and the platelet marker CD41a, though these changes were not significant after correction for multiple comparisons. These findings point to potential dysregulation of B cell and platelet activation or homeostasis in ME/CFS, which warrants validation in a replication cohort and further exploration of potential mechanisms underlying the association.

 

i think it is a gret idea to compare severities. i wonder if ev action could be studied in vitro?

> though these changes were not significant after correction for multiple comparisons

what makes this significant? i assumed xkcd jelly bean comic would apply here. i.e. not significant.

 

With 10 severe and 10 mild ME/CFS patients, the study seems to small to conclude anything unfortunately.

 

Shouldn't the length of time the patient was ill be factored in as well?

The 'mild' and 'severe' group doesn't have much significance when we all experience PEM. I don't experience unrefreshing sleep. Am I considered 'mild'?

 

Why should it?

This is how they defined severity. Inclusion criteria was Fukuda.

The MFI-20 questions are (click to expand image)

Link to original document, https://www.med.upenn.edu/cbti/asse.../Multidimensional Fatigue Inventory (MFI).pdf

So how you would be considered would depend for this study on your MFI-20 score.

 

I so hate questionnaires. They can be misinterpreted. Or perhaps that’s my impression. Take for instance the statement “i feel like doing all sorts of nice things”- are they checking for depression? What if you say yes, i feel like doing all sorts of things but hell no, my body won’t let me? And then another person would say no i don’t feel like it because they know they are too sick for anything?

 

I can't understand the scoring for the questions. If you get 5 for not true "I feel fit!" but then you score 1 for true "Physically I can do very little" then you get the same score if you are an athlete as if you have ME.

Am I missing something or is this worse than the Chalder scale?

 

I considered my ME mild and I definitely experience unrefreshing sleep.

 

The intro to the linked MFI questionnaire says

Does anyone know what validation study they refer to? Because, applied to ME, some of the MFI questions are extremely open to different interpretations. Not to mention patronisingly phrased, e.g. what has 'feeling' to do with anything in for example "Physically, I feel only able to do a little"? This MFI, like most other questionnaires, should never have passed validation for ME.

 

Well this paper is referenced at the bottom of the linked questionnaire, so presumably it is this one

The multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue

Abstract
The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure fatigue. It covers the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. This new instrument was tested for its psychometric properties in cancer patients receiving radiotherapy, patients with the chronic fatigue syndrome, psychology students, medical students, army recruits and junior physicians. We determined the dimensional structure using confirmatory factor analyses (LISREL's unweighted least squares method). The hypothesized five-factor model appeared to fit the data in all samples tested (AGFIs > 0.93). The instrument was found to have good internal consistency, with an average Cronbach's alpha coefficient of 0.84. Construct validity was established after comparisons between and within groups, assuming differences in fatigue based on differences in circumstances and/or activity level. Convergent validity was investigated by correlating the MFI-scales with a Visual Analogue Scale measuring fatigue (0.22 < r < 0.78). Results, by and large, support the validity of the MFI.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/002239999400125O

 

Thanks Andy.

So this paper is from 1995. I don't have access to the full paper but the publicly available references include:

Based on those two factors I think it is reasonable to assume that the MFI has not been validated for ME/CFS as we would define it today.
A poor choice of questionnaire (admittedly finding a good one is an issue but there are now better options to establish severity like Bateman's time upright/feet on ground). Also disappointing that in 2022 they still went with Fukuda. But overall I agree with Hutan (my bolding)