An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques, 2025, Germain et al.

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by serious physical and cognitive impairments. Recent research underscores the role of immune dysfunction, including the role of autoantibodies, in ME/CFS pathophysiology. Expanding on previous studies, we analyzed 7542 antibody–antigen interactions in ME/CFS patients using two advanced platforms: a 1134 autoantibody Luminex panel from Oncimmune and Augmenta Bioworks, along with Rapid Extracellular Antigen Profiling (REAP), a validated high-throughput method that measures autoantibody reactivity against 6183 extracellular human proteins and 225 human viral pathogen proteins. Unlike earlier reports, our analysis of 172 participants revealed no significant differences in autoantibody reactivities between ME/CFS patients and controls, including against GPCRs such as β-adrenergic receptors. However, subtle trends in autoantibody ratios between male and female ME/CFS subgroups, along with patterns of herpesvirus reactivation, suggest the need for broader and more detailed exploration.

Link to study:
https://www.mdpi.com/1422-0067/26/6/2799

 

Contrary to what the authors write I think one can actually say that "GPCR AAb Results Do Align with Previous Findings". How does the REAP assay compare to ANA tests where there have been some mixed evidence suggesting the possibility of higher levels in ME/CFS?

 

Could you clarify what you mean, where there differences in GPCR AAb in this study?

 

Good grief: clear reporting of a negative result, including that it contradicts earlier positive findings. That might seem like a backward step, but I think it’s huge progress, not least because Arnaud Germain is an impressive researcher from a big group (Maureen Hanson’s)

 

It fits very well with the picture of ME/CFS immunology that is crystallising in my mind.
But it doesn't necessarily mean that B cells are not involved.

ANA tests come in all sorts of methodological variants. I suspect that reports of more ANAs in ME/CFS may have been due to bias problems that are so hard to exclude. An increase in rate of ANA would not have been surprising but I think this study makes it unlikely. There are thousands of antigens that will come up as ANA. This study just looked at proteins and not DNA. DNA is an important antigen in lupus but probably does not often occur in isolation.

 

No. But as far as I can still they weren't really in other studies either. One study will have had marginally higher levels, but the next might have has marginally lower levels so it evened out pretty fairly over most studies as far as I can tell.

 

What are these “IgG with inflammatory glycan patterns, for example, afucosylated IgG.”?

From here:
“Given our results and the existence of discrepant reports of elevated and lower levels of ADRB2 AAb levels, as addressed in the previous paragraph, the success of IA in responding ME/CFS subjects could be attributed to other AAb that are not yet identified or through the clearance of IgG with inflammatory glycan patterns, for example, afucosylated IgG.“

 

No idea what any of this work means, but at least I've gained a glorious new word!

 

Please dear God, don’t let me be afucosylated, anything but that!

Was asking about the IGG because we saw that in the Fluge studies, the patients who recovered started and ended with lower IGG levels.

 

Have you elaborated this anywhere? Would love to read more.

 

Hang on a bit. Not quite yet.

 

During acute inflammatory episodes and also in rheumatoid disease the 'sugar decoration' of the IgG protein may be defective. Lots of proteins normally have sugar decoration in the form of oligosaccharide chains - chains of sugar molecules like sialic acid, fucose, galactose...

Afucosylated means that it is missing the end fucose.

While interesting I am not sure that it has ever been shown that this sugar stripping means anything very important.