Fibromyalgia: transfer of patient IgG antibodies produce FM symptoms in mice

[WantedAlive]

Passive transfer of fibromyalgia symptoms from patients to mice

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.

I'm always dubious about symptom evaluation in mice. I guess it adds weight to the autoimmune theory for both FM and likely ME/CFS. But I believe some ME/CFS patients have had plasmapharesis without success, is that true?

 

[Martin aka paused||M.E.]

Passive transfer of fibromyalgia symptoms from patients to mice




I'm always dubious about symptom evaluation in mice. I guess it adds weight to the autoimmune theory for both FM and likely ME/CFS. But I believe some ME/CFS patients have had plasmapharesis without success, is that true?

If you are referring to the Carmen Scheibenbogen study yes, there were mixed results. But I heard of one patient who always went into full remission for three weeks after each session

 

[WantedAlive]

Carmen Scheibenbogen study

Thanks, I'll go back and look at that. Even in the patient it worked, 3 weeks seems an extremely brief remission after plasmapharesis. I don't even think the mRNA vaccine could pump out antibodies that quickly! There must be something else to it surely.

 

[Martin aka paused||M.E.]

Thanks, I'll go back and look at that. Even in the patient it worked, 3 weeks seems an extremely brief remission after plasmapharesis. I don't even think the mRNA vaccine could pump out antibodies that quickly! There must be something else to it surely.

The study was paid by Fresenius and unfortunately very expensive so it was only a very small group and there was no follow-up study bc Fresenius declined to donate. That being said, the erased AAB can be found in only a subgroup of patients (30% - I'm negative). Interestingly a new study on Long Covid showed overlapping AAB.

 

[nerd]

But I believe some ME/CFS patients have had plasmapharesis without success, is that true?

The disease is not "only" in the plasma. It is also in the cells. The plasma can only serve as a dissolving buffer. What might really have potential is HDACi for viral reactivation, miRNA release, cell cycle regulation, and subsequent/parallel antiviral therapy and plasmapheresis. This would have to repeated a couple of times for sufficient clearance potential.

 

[Martin aka paused||M.E.]

The disease is not "only" in the plasma. It is also in the cells. The plasma can only serve as a dissolving buffer. What might really have potential is HDACi for viral reactivation, miRNA release, cell cycle regulation, and subsequent/parallel antiviral therapy and plasmapheresis. This would have to repeated a couple of times for sufficient clearance potential.

The problem is that such a trial would be very costly I think

 

[nerd]

The problem is that such a trial would be very costly I think

Most definitely, plasmapheresis is very expensive. It will be much cheaper to just remove the blood and take electrolytes (preferably via infusion) and anemia medications while monitoring the blood cell count. Unfortunately, some ME patients also suffer from mild anemia already, so this isn't applicable to them. This kind of therapy is also stigmatized because it has been used in medieval times by the Catholic Church, kind of.

 

[Martin aka paused||M.E.]

Most definitely, plasmapheresis is very expensive. It will be much cheaper to just remove the blood and take electrolytes (preferably via infusion) and anemia medications while monitoring the blood cell count. Unfortunately, some ME patients also suffer from mild anemia already, so this isn't applicable to them. This kind of therapy is also stigmatized because it has been used in medieval times by the Catholic Church, kind of.

Yeah it has some flavor of it at least

 

[Legolas]

https://www.sciencedaily.com/releases/2021/07/210701120703.htm

New research has shown that many of the symptoms in fibromyalgia syndrome (FMS) are caused by antibodies that increase the activity of pain-sensing nerves throughout the body. The results show that fibromyalgia is a disease of the immune system, rather than the currently held view that it originates in the brain.

 

[Alvin2]

A very interesting study.
I hope there are scientists following up on this, pursuing replication and working on new treatments.

 

[Pyrrhus]

"The results show that fibromyalgia is a disease of the immune system, rather than the currently held view that it originates in the brain."

Whatever reporter wrote that didn't even read this study.

This study clearly demonstrates that fibromyalgia is a neuroimmune condition, involving both the immune system and the nervous system.

EDIT:
Anyone interested in the diagnostic criteria for fibromyalgia should see this discussion:

Fibromyalgia (FM): Diagnostic Criteria
https://forums.phoenixrising.me/threads/fibromyalgia-fm-diagnostic-criteria.86692/

 

[Canned]

But I believe some ME/CFS patients have had plasmapharesis without success, is that true?

Yes, I had 4 plasmapharesis in 7 days without any success.

 

[Pyrrhus]

Related publications on fibromyalgia research:

Identification of a MicroRNA Signature for the Diagnosis of Fibromyalgia (Cerda et al., 2015)
https://forums.phoenixrising.me/thr...ture-for-the-diagnosis-of-fibromyalgia.36480/

Fibromyalgia Is Correlated with Retinal Nerve Fiber Layer Thinning (Garcia-Martin et al. 2016)
https://forums.phoenixrising.me/thr...-of-fibromyalgia-patients.61667/#post-2321474

Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation (Albrecht et al. 2019)
https://forums.phoenixrising.me/thr...-of-fibromyalgia-patients.61667/#post-2321470

Characterization of dermal skin innervation in fibromyalgia syndrome (Evdomikov et al., 2020)
https://forums.phoenixrising.me/thr...ervation-in-fibromyalgia-syndrome-2020.79404/

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia (Verma et al., 2021)
https://forums.phoenixrising.me/thr...-axis-in-fibromyalgia-verma-et-al-2021.87598/

Pain-related post-exertional malaise in ME/CFS and Fibromyalgia: A systematic review and three-level meta-analysis (Barhorst et al., 2021)
https://forums.phoenixrising.me/thr...evel-meta-analysis-barhorst-et-al-2021.85991/

 

[Pyrrhus]

Below is a diagram that might help to understand this paper:

The paper describes how antibodies from patients with fibromyalgia attach to the dorsal root ganglia (DRG), which are the pain-sensing nerve roots that run along the spinal cord.

This finding leads to the important question:

What inflammation may be happening in these spinal nerve roots in order to trigger production of these antibodies in fibromyalgia patients?

 

[Apollonia]

Obviously, these mice need GET and CBT.

 

[Pyrrhus]

What inflammation may be happening in these spinal nerve roots in order to trigger production of these antibodies in fibromyalgia patients?

For possibly related information about how an infection in one location can generate antibodies that target the tissue surrounding the location of the infection, see the discussion of epitope spreading in this discussion:

How Viruses Can Cause Autoimmunity
https://forums.phoenixrising.me/threads/how-viruses-cause-autoimmunity.86598/

 

[lenora]

If you are referring to the Carmen Scheibenbogen study yes, there were mixed results. But I heard of one patient who always went into full remission for three weeks after each session

Hello @MartinakapausedME......I was thinking about you the other day! Hopefully, your latest treatment went well (please let us know), and I wanted to extend my best wishes to you. You're trying very hard and it's the best time to do it....when you're young. I'm also hoping that your lovely fiancee is well. Yours, Lenora.

 

[lenora]

Hello Everyone......Yes, I would probably describe FM as a disease of the neuroimmune system as @Pyrrhus described.

After I had an old-fashioned shunt (which promptly blocked), inserted in my spinal cord (back in the mid 1980's), I became "frozen" in my body. I've never experienced such pain in my life. A no. of years later, I had brain surgery....there is no comparison of the amount of pain suffered. Not much in comparison to cord surgery. I expected it, but it passed within 2-3 wks.

Prior to that I had started taking vitamins, eating well, building my body up and my own "go to" walking, if possible. Just gentle walking when I could finally move. (Bear in mind I was much younger then.) One other thing: I missed PT b/c of illness at one point....and noticed that my body did much better when it wasn't handled as much. This was very apparent and I told my Dr. He made note of it b/c he had many patients who suffered from the same symptoms. All had cord or brain problems, many with horrid diseases.

I've had bad attacks of FM over the years, some stay longer than others. I can't think of any treatment that I haven't tried, both medical and alternative. The very best for me is totally deadening the pain with those Ace ice packs I keep writing about. Funny, as my neurologist told me that ice would probably help allay the pain much better than anything...and that was back then years ago.

Lyrica has also helped in keeping the symptoms under control somewhat. There are days when it's really bad, and it's hard to explain what can set it off. I'm getting weaker with age, but things like the hard nodules have disappeared, even the swollen nodes that were also such a challenge. I'm 75 so I'm saying that the symptoms of FM have come (for a long spell) in me, gone away and then reappeared.

Be hopeful for yourselves....it took me many years to rid myself of most of the symptoms, not all, and I probably carry some as just part of my many conditions. After all, it has been well over 35 years-40 yrs. ago. Many of you are much younger than I was even then (I'm now 75).

Younger members should look at this with hope; and the knowledge that we had nothing all that time ago. I just happened upon a neurologist who believed me, handed me as many studies as he could, took it all quite seriously and I was referred to a PT specialist in myofascial disease. This was unheard of at the time. The only treatment we had was small doses of elavil, until gabapentin came along many years later. Lyrica is a child of gaba. I trust this will give you some hope for the future. Sincerely wishing you all well. Yours, Lenora.