Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, Bastos et al

Nightsong

Nightsong

Senior Member (Voting Rights)
Abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex heterogeneous multiorgan disease that can have severe impact on individuals' quality of life. Diagnosis of ME/CFS is based on symptom presentation, and a significant goal for the field is to establish meaningful subtypes. The heterogeneity in the literature suggests that individuals living with ME/CFS may suffer from overlapping but different underlying pathophysiological mechanisms.

We enrolled 40 participants with ME/CFS and 41 matched healthy control subjects at the Bragée Clinic in Sweden. We assessed plasma samples from both ME/CFS cases and control groups and cerebrospinal fluid (CSF) samples from individuals with ME/CFS. We investigated dysregulated pathways and disease profiles through clinical questionnaires; multiplex analyses of cytokines, hormones, and matrix metalloproteinases; pathogen seroreactivity through peptide display bacteria libraries; and high-throughput microarray for autoantibodies. All samples used were from humans.

We show altered interaction patterns between circulating biological factors in plasma of ME/CFS participants. Our analysis of CSF from individuals with ME/CFS revealed different immunotypes of disease. We found 2 patient clusters based on matrix metalloproteinases profiles. The subgroups had similar clinical presentation but distinct pathogen exposure and CSF inflammatory profiles. Our findings shed light on ME/CFS immune phenotypes and generate hypotheses for future research in disease pathogenesis and treatment development by exploring disease subgroups.

Link | PDF (The Journal of Immunology, May 2025, open access)
 
Jonathan Edwards said:
They say nothing in the abstract about any differences from normal controls so maybe there weren't any?
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They do briefly mention some differences in the paper

. Factor P was the autoantigen with the highest differential IgM reactivity, with a log2(fold change) of 0.47 (P ¼ 0.049) (Fig. S2B). Additionally, anti-factor P IgM was significantly lower in participants with ME/CFS when compared with healthy control subjects (P ¼ 0.0232). (Fig. S2C).
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And fig 2 seems to show some differences - but I'm not convinced I'm understanding what they are saying.

I seem to remember Lipkin did some analysis of CSF.
 
Wrote a brief summary on social media:
https://twitter.com/user/status/1924407954670846155


1) Interesting collaboration between the Iwasaki team and the Bragée clinic in Sweden. Their conclusion: "when evaluating previous pathogen exposure, we found that ME/CFS and healthy individuals did not differ in exposure to most assessed pathogens."

2) The authors used the serum epitope repertoire analysis (SERA) assay in 39 ME/CFS patients and 40 controls. SERA leverages a database of thousands of infected vs. seronegative control subjects to determine past exposure to a pathogen using antibody repertoires.

3) The study also screened autoantibody reactivities. For 57 out of 118 antigens, significantly higher IgM autoantibody reactivities were detected in healthy individuals compared to participants with ME/CFS. So reactivity was LOWER in ME/CFS but effect sizes were quite small.

4) The rest of the paper focuses on subgrouping ME/CFS patients based on cerebrospinal fluid analysis (which unfortunately was not measured in control subjects).
 
The problematic aspects of the diagnostics at Bragée ME Center have been discussed on this forum before, and also the various subgroups that Bragée ME Center made up very early on and added onto the ICD code in the patients' medical records.

Just quickly mentioning it here, because a lot of people who wouldn't have gotten a ME diagnosis from the previous biomed ME clinics in Sweden, such as Stora Sköndal, have been diagnosed with ME by Bragée.

This means that there is a lot (a lot!) more heterogenity among patients with a ME diagnosis in Sweden nowadays, compared to before Bragée ME Center existed. It's very noticeable to those of us who have been active in the patient community for a long time.

Or in other words, to be blunt, I'm not so sure that all the people who have been diagnosed with ME by Bragée ME Center would receive the same diagnosis from other ME specialists based on diagnostic criteria like CCC and similar. It's something worth being aware of, I think.
 
I think this article is about the paper in this thread:

PolyBio and WE&ME supported study identifies two distinct ME/CFS subtypes
A PolyBio-supported study published today in the Journal of Immunology sheds new light on the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) disease process. This includes the identification of two biologically distinct ME/CFS subgroups based on cerebrospinal fluid (CSF) markers. The research was performed by a collaborative team of researchers connected via PolyBio Research Foundation. Primary analysis occurred at Dr. Akiko Iwasaki’s Yale University laboratory, with study samples obtained at the Bragee Clinic in Sweden. PolyBio co-founders Dr. Amy Proal and Dr. Michael VanElzakker facilitated the collaboration and helped with data interpretation and contextualization.

More specifically, the team performed comprehensive immune profiling on blood and CSF collected from individuals with ME/CFS. They measured cytokine and hormone levels, pathogen protein antibody responses, and autoantibody profiles in patient samples. They identified two distinct immunotypes within the ME/CFS cohort based on CSF matrix metalloproteinase (MMP) levels. One subgroup (Cluster 1) exhibited elevated levels of MMP-1, MMP-2, and MMP-10, as well as increased concentrations of several cytokines. These markers may reflect a disease variant driven by central nervous system inflammation. The other subgroup (Cluster 2) showed distinct correlations between immune markers and higher rates of joint hypermobility.
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ahimsa said:
I think this article is about the paper in this thread:

PolyBio and WE&ME supported study identifies two distinct ME/CFS subtypes
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Highlighting the following given discussion elsewhere on possible neuron/immune involvement in ME/CFS.
The study also noted changes in specific immune pathways. ME/CFS participants showed altered cytokine correlation patterns, including disrupted interactions involving fractalkine—a chemokine involved in neuron-microglia communication—and eotaxin, a molecule implicated in aging and neurodegeneration. These disturbances may influence neuroinflammation and symptom development.
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