ME/CFS Science
@mecfsskeptic.bsky.social
In-depth analysis of research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Formerly known as ME/CFS Skeptic.
https://mecfsscience.org/
https://mecfsscience.org/
5) The presentation by Peluso was at the Fall symposium of Polybio and can be watched here:
polybio.org/fall-202...
More info about the Project can be found here:
polybio.org/projects...
polybio.org/fall-202...
More info about the Project can be found here:
polybio.org/projects...
November 27, 2025 at 9:37 AM
5) The presentation by Peluso was at the Fall symposium of Polybio and can be watched here:
polybio.org/fall-202...
More info about the Project can be found here:
polybio.org/projects...
polybio.org/fall-202...
More info about the Project can be found here:
polybio.org/projects...
4) Many of the complex analyses, such as immune phenotyping, imaging, and virology, will be supported by top experts from other Polybio collaborations.
CHIME hopes to start in January 2026 with in-person meetings in San Francisco.
CHIME hopes to start in January 2026 with in-person meetings in San Francisco.
November 27, 2025 at 9:37 AM
4) Many of the complex analyses, such as immune phenotyping, imaging, and virology, will be supported by top experts from other Polybio collaborations.
CHIME hopes to start in January 2026 with in-person meetings in San Francisco.
CHIME hopes to start in January 2026 with in-person meetings in San Francisco.
3) The study will also collect various questionnaires such as FUNCAP and objective measures including neurocognitive testing grip strength, an active stand, EndoPAT (for endothelial dysfunction), and home sleep testing.
November 27, 2025 at 9:37 AM
3) The study will also collect various questionnaires such as FUNCAP and objective measures including neurocognitive testing grip strength, an active stand, EndoPAT (for endothelial dysfunction), and home sleep testing.
2) CHIME stands for 'Chronic Infection and Inflammation in ME/CFS' and is funded by PolyBio.
Much of the rationale for the study stems from John Chia's work on persistent enteroviruses in ME/CFS. CHIME wants to check if these results can be replicated using newer technologies.
Much of the rationale for the study stems from John Chia's work on persistent enteroviruses in ME/CFS. CHIME wants to check if these results can be replicated using newer technologies.
November 27, 2025 at 9:37 AM
2) CHIME stands for 'Chronic Infection and Inflammation in ME/CFS' and is funded by PolyBio.
Much of the rationale for the study stems from John Chia's work on persistent enteroviruses in ME/CFS. CHIME wants to check if these results can be replicated using newer technologies.
Much of the rationale for the study stems from John Chia's work on persistent enteroviruses in ME/CFS. CHIME wants to check if these results can be replicated using newer technologies.
8) You can support OMF's work by donating using this form:
www.omf.ngo/?form=do...
All donations to OMF are tripled until December 2, 2025.
www.omf.ngo/?form=do...
All donations to OMF are tripled until December 2, 2025.
OMF Home - Open Medicine Foundation
ME/CFS & Long COVID are life-altering illnesses. Together, we can move research further, faster.
www.omf.ngo
November 26, 2025 at 9:34 AM
8) You can support OMF's work by donating using this form:
www.omf.ngo/?form=do...
All donations to OMF are tripled until December 2, 2025.
www.omf.ngo/?form=do...
All donations to OMF are tripled until December 2, 2025.
7) The video also includes insights from another OMF director, Dr. Wenzhong Xiao, who comments about current data and exploring treatment options, including supplements.
Link:
Link:
An Interview with Chris Armstrong, PhD and Wenzhong Xiao, PhD
In an interview with Dr. Chris Armstrong and Dr. Wenzhong Xiao, two of OMF’s Directors, they talk about what they think is going on in ME/CFS, including differences in producing energy and the immune and central nervous systems being out of balance.
All donations to OMF are TRIPLED until December 2
www.youtube.com
November 26, 2025 at 9:34 AM
7) The video also includes insights from another OMF director, Dr. Wenzhong Xiao, who comments about current data and exploring treatment options, including supplements.
Link:
Link:
6) They are exploring this further in the large BioQuest study. It plans to measure many proteins and metabolites in blood samples of up to 1000 patients and controls that have already been collected.
More info about this study here:
More info about this study here:
Update: A large-scale ME/CFS biomarker project (BioQuest) - Open Medicine Foundation
Explore OMF’s BioQuest, a large-scale ME/CFS biomarker study looking at metabolomics, proteomics, and cytokines.
www.omf.ngo
November 26, 2025 at 9:33 AM
6) They are exploring this further in the large BioQuest study. It plans to measure many proteins and metabolites in blood samples of up to 1000 patients and controls that have already been collected.
More info about this study here:
More info about this study here:
5) Dr. Armstrong connects this to his findings of metabolomics studies, which OMF focuses on. They found changes in amino acids and lipids in ME/CFS: those two things seem to stand out.
And these look like changes in the fuel for the ATP engines.
And these look like changes in the fuel for the ATP engines.
November 26, 2025 at 9:33 AM
5) Dr. Armstrong connects this to his findings of metabolomics studies, which OMF focuses on. They found changes in amino acids and lipids in ME/CFS: those two things seem to stand out.
And these look like changes in the fuel for the ATP engines.
And these look like changes in the fuel for the ATP engines.
4) So, as a general hypothesis, he thinks about an energy inefficient system, but with added things that weigh it down and reduce the energy profile within the patient.
November 26, 2025 at 9:33 AM
4) So, as a general hypothesis, he thinks about an energy inefficient system, but with added things that weigh it down and reduce the energy profile within the patient.
3) In addition to that, there might be a lot of bodily processes that ME/CFS patients can't control that use up a lot of ATP, such as immune activation or inappropriate release of adrenaline for POTS.
November 26, 2025 at 9:33 AM
3) In addition to that, there might be a lot of bodily processes that ME/CFS patients can't control that use up a lot of ATP, such as immune activation or inappropriate release of adrenaline for POTS.
2) By fuel, he means the supply from the blood of nutrients and oxygen, but also the cleaning up of byproducts from those fuels. These are all factors that can make energy production less efficient.
November 26, 2025 at 9:33 AM
2) By fuel, he means the supply from the blood of nutrients and oxygen, but also the cleaning up of byproducts from those fuels. These are all factors that can make energy production less efficient.
The paper says: "We utilised Cre-driven diphtheria toxin A (DTA) to selectively deplete Mrgprb2 (b2)-positive mast cells, specifically targeting all connective tissue mast cells, without affecting the circulating mucosal mast cells."
Suspect this would be too dangerous in humans.
Suspect this would be too dangerous in humans.
November 25, 2025 at 12:54 PM
The paper says: "We utilised Cre-driven diphtheria toxin A (DTA) to selectively deplete Mrgprb2 (b2)-positive mast cells, specifically targeting all connective tissue mast cells, without affecting the circulating mucosal mast cells."
Suspect this would be too dangerous in humans.
Suspect this would be too dangerous in humans.
7) Link to the paper:
Sanchez et al. 2025. The sensitising effect of IgG in fibromyalgia syndrome is mediated by Mrgprb2 in mast cells.
Sanchez et al. 2025. The sensitising effect of IgG in fibromyalgia syndrome is mediated by Mrgprb2 in mast cells.
The sensitising effect of IgG in fibromyalgia syndrome is mediated by Mrgprb2 in mast cells
Fibromyalgia syndrome (FMS) is characterized by elevated levels of immunoglobulin G (IgG), altered bowel habits, and increased pain sensitivity, suggesting immune dysregulation, but the exact mechanism remains unclear. Here, we found that FMS-IgG binds to mast cells in a MRGPRX2/b2-dependent manner, leading to mast cell recruitment and IL-6 secretion. Transferring serum-IgG from FMS patients to mice induced FMS-like symptoms and increased skin mast cells, indicating that FMS-IgG acts through mast cell activation. The ablation of mice Mrgprb2 mast cells or deleting Mrgprb2 receptors prevented IgG-induced heightened sensitivity to mechanical and cold stimuli. Stimulating human LAD2 cells with FMS IgG elicited MRGPRX2-dependent IL-6 production. Consistent with mice findings, mast cell density and tryptase levels increased in human FMS skin samples compared to healthy controls. Taken together our results suggests that FMS IgG mediates hypersensitivity via activation of mast cells bearing the MRGPRX2 receptor and that these cells are a potential therapeutic target.
### Competing Interest Statement
X.D. is the scientific founder of and consultant for Escient Pharmaceuticals, a pharmaceutical company developing drugs targeting Mrgprs. X.D. collaborates with GlaxoSmithKline (GSK) on Mrgpr-related projects unrelated to this manuscript. Other authors declare no competing interests.
Howard Hughes Medical Institute, https://ror.org/006w34k90
Pain Relief Foundation, https://ror.org/0017mh436
Versus Arthritis, https://ror.org/02jkpm469, 22471
www.biorxiv.org
November 25, 2025 at 11:05 AM
7) Link to the paper:
Sanchez et al. 2025. The sensitising effect of IgG in fibromyalgia syndrome is mediated by Mrgprb2 in mast cells.
Sanchez et al. 2025. The sensitising effect of IgG in fibromyalgia syndrome is mediated by Mrgprb2 in mast cells.
6) One of the more interesting findings is that CRPS antibodies caused pain sensitivity, but that deleting mast cells with the Mrgprb2 receptors did not reduce the sensitivity, as was the case with fibromyalgia antibodies.
This suggests different mechanisms are involved.
This suggests different mechanisms are involved.
November 25, 2025 at 11:05 AM
6) One of the more interesting findings is that CRPS antibodies caused pain sensitivity, but that deleting mast cells with the Mrgprb2 receptors did not reduce the sensitivity, as was the case with fibromyalgia antibodies.
This suggests different mechanisms are involved.
This suggests different mechanisms are involved.
5) This is from a preprint (not peer-reviewed yet) from May 2025 that uses small sample sizes. But the results are fascinating and may be relevant to similar experiments with antibodies of Long Covid and ME/CFS patients.
November 25, 2025 at 11:05 AM
5) This is from a preprint (not peer-reviewed yet) from May 2025 that uses small sample sizes. But the results are fascinating and may be relevant to similar experiments with antibodies of Long Covid and ME/CFS patients.
4) Further experiments showed that the antibodies bind to mast cells through a specific receptor called MRGPRX2 in humans (and its equivalent Mrgprb2 in mice).
When this receptor was deleted, there was no longer an increase in pain sensitivity.
When this receptor was deleted, there was no longer an increase in pain sensitivity.
November 25, 2025 at 11:05 AM
4) Further experiments showed that the antibodies bind to mast cells through a specific receptor called MRGPRX2 in humans (and its equivalent Mrgprb2 in mice).
When this receptor was deleted, there was no longer an increase in pain sensitivity.
When this receptor was deleted, there was no longer an increase in pain sensitivity.
3) The researchers also confirmed historical findings of strongly increased skin mast cell density in the skin of fibromyalgia patients compared to controls.
November 25, 2025 at 11:05 AM
3) The researchers also confirmed historical findings of strongly increased skin mast cell density in the skin of fibromyalgia patients compared to controls.
2) The antibodies of fibromyalgia patients bind more strongly to mast cells than antibodies of healthy controls or patients with complex regional pain syndrome (CRPS).
November 25, 2025 at 11:05 AM
2) The antibodies of fibromyalgia patients bind more strongly to mast cells than antibodies of healthy controls or patients with complex regional pain syndrome (CRPS).
Not aware of any ME/CFS studies using this.
November 24, 2025 at 4:48 PM
Not aware of any ME/CFS studies using this.
10) The PolyBio Fall 2025 Symposium was recorded and can be watched here:
www.youtube.com/watc...
We haven't seen it yet, but plan to in the near future. Feel free to indicate which presentations we shouldn't miss!
www.youtube.com/watc...
We haven't seen it yet, but plan to in the near future. Feel free to indicate which presentations we shouldn't miss!
PolyBio Fall 2025 Symposium
Please note that many speakers are featuring unpublished, pilot data. The data should be taken in context that it may change over time as more samples are analyzed, and projects are finalized.
0:00: Amy Proal--An overview of PolyBio’s complex chronic illness research & clinical trials program
10:0
www.youtube.com
November 23, 2025 at 2:01 PM
10) The PolyBio Fall 2025 Symposium was recorded and can be watched here:
www.youtube.com/watc...
We haven't seen it yet, but plan to in the near future. Feel free to indicate which presentations we shouldn't miss!
www.youtube.com/watc...
We haven't seen it yet, but plan to in the near future. Feel free to indicate which presentations we shouldn't miss!