Preprint Abnormal T-Cell Activation And Cytotoxic T-Cell Frequency Discriminates Symptom Severity In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome,'25,Lee

https://www.medrxiv.org/content/10.1101/2025.01.02.24319359v1

Abnormal T-Cell Activation And Cytotoxic T-Cell Frequency Discriminates Symptom Severity In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Ji-Sook Lee1,3, Eliana Lacerda2, Caroline Kingdon 2, Giada Susannini1, Hazel M Dockrell1, Luis Nacul2*, Jacqueline M Cliff3*

*These authors contributed equally to this work.

1Department of Infection Biology and 2Clinical Research Department, Faculty of Infectious and Topical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT. 3Centre for Inflammation Research and Translational Medicine, and Division of Biosciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, UB8 3PH. Corresponding Author: Dr Jacqueline Cliff, Division of Biosciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, UB8 3PH, United Kingdom, +44 (0) 1895 268803


Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating but poorly-understood disease. ME/CFS symptoms can range from mild to severe, and include immune system effects alongside incapacitating fatigue and post-exertional disease exacerbation.

In this study, we examined immunological profiles of people living with ME/CFS by flow cytometry, focusing on cytotoxic cells, to determine whether people with mild/moderate (n= 43) or severe ME/CFS (n=53) expressed different immunological markers.

We found that people with mild/moderate ME/CFS had increased expression of cytotoxic effector molecules alongside enhanced proportions of early-immunosenescence cells, determined by the CD28-CD57- phenotype.

In contrast, people with severe ME/CFS had higher proportions of activated circulating lymphocytes, determined by CD69+ and CD38+ expression, and expressed more pro-inflammatory cytokines, including IFNγ, TNF and IL-17, following stimulation in vitro.

These changes were consistent across different cell types including CD8+ T cells, mucosal associated invariant T cells and Natural Killer cells, indicating generalised altered cytotoxic responses across the innate and adaptive immune system .

These immunological differences likely reflect different disease pathogenesis mechanisms occurring in the two clinical groups, and opening up opportunities for the development of prognostic markers and stratified treatments.

 

Could the differences be due to different lifestyles (activity, diet, etc) and different exposure to pathogens? I'm guessing that someone with mild ME would encounter more variety of microbes than a bedridden person, and thus have different immune system challenges.

 

This is really interesting phrasing for PEM, and I have to say, as a severe person, it encompasses my experience far better than “PEM”.

 

I know this isn’t a massive sample size but it’s refreshingly large compared to the 5-10 patients in most studies.

Interesting hypothesis. Sounds like a possible confounding factor. Although pwSevere ME still often have quite a bit of pathogen spread due to interaction with caregivers, in fact, a severe person requiring a caregiver might end up having more human (=pathogen) contact that a mostly housebound mild/moderate person who lives on their own.

 

Except that if we don't know what the 'disease' is or whether there is one or two or six it doesn't mean much does it? The paper is making an argument for there being two routes to symptoms (moderate and severe being different) or, if you like, two different diseases.

 

Glad they didn't go with overactivation.

 

Certainly doesn’t work in french, but to be fair translating the underlying words gives EMPE.

I’m not aware of what PEDE could mean in english? In French “Pede” is a really derogatory word for queer people, but I don’t think I’ve ever heard that in english?

 

Who knows what it might be taken for in the UK, if ignorance is willing. One thinks of the lady doctor here in the UK who was targeted some years back because a small group of people confused ‘paediatrician’ with ‘pedophile’.

 

To be fair paed has the same root as ped in pedophile, which comes from ancient greek “paid” meaning children.

But yeah it’s kind of baffling people will confuse words with pedophile.