Pathophysiological Basis of Fibromyalgia: IgG Autoantibodies Cause Pain

[Gemini]

Researchers at Kings College, London believe they've determined the pathohysiological basis of pain in FM.

In an innovative and rigorous experiment described by Dr. David Andersson at the IIME Conference May 31 2019 human IgG from healthy controls and FM patients was transferred into mice-- provoking pain in the animals that received FM patient, but not healthy control, IgG.

It was further determined IgG antibodies sensitize "peripheral" nociceptors and when antibodies are removed pain subsides. A diagnostic test and specific FM treatments that deplete antibodies, for example, could follow.

Andersson would like to repeat the study using ME/CFS patient IgG as ME/CFS and FM have similar symptoms. This caught the attention of Dr. Fluge [ME Rituxan trial] also presenting at IIMEC14.

Video of Dr. Andersson's entire presentation is here:
www.investinme.org/IIMEC14.shtml

 

[pattismith]

Passive transfer of fibromyalgia pain from patients to mice
David A. Andersson King’s College London, Wolfson CARD, Institute of Psychiatry, Psychology & Neuroscience, Guy’s Campus, SE1 1UL

SUMMARY
Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain and tenderness1,2. The etiology and pathophysiology of fibromyalgia are unknown and there are no effective treatments. Here we show that sensory hypersensitivity in FMS is caused by autoantibodies that act by sensitizing nociceptive sensory neurons.
Administration of IgG from FMS patients increased mouse pain sensitivities to stimulation with mechanical pressure and cold. In contrast, transfer of IgG depleted samples from FMS patients or IgG from healthy control subjects had no effect on pain sensitivity.
Sensory nerve fibres in ex vivo skin-nerve preparations from mice treated with FMS IgG were hypersensitive to mechanical stimulation. Immunohistochemical analysis revealed that IgG from FMS patients specifically labeled satellite glial cells and myelinated fibre tracts, as well as a small number of macrophages and endothelial cells in mouse dorsal root ganglia but not skin, muscle, spinal cord and brain. Our results demonstrate that fibromyalgia pain is caused by IgG autoantibodies that sensitize peripheral nociceptive afferents neurons and suggest that therapies that reduce patient IgG titres may be effective treatments of fibromyalgia pain.

 

[Gemini]

Passive transfer of fibromyalgia pain from patients to mice
David A. Andersson King’s College London, Wolfson CARD, Institute of Psychiatry, Psychology & Neuroscience, Guy’s Campus, SE1 1UL

Nice find @pattismith.

By any chance do you have a citation or link to the full article?

 

[Gemini]

Dr. Andersson indicated in his IIMEC14 talk that a next step is to try to identify the antigen.

Believe this refers to "Experimental studies of human pathogen" on the "Our Conclusions" chart shown above. Looking forward to details about his efforts to do this and the result.

In his IIMEC14 talk Dr. Bevan described the ongoing heated debate in the FM field about the source of FM pain--central versus peripheral. He references Andersson's work which could be a major breakthrough if it holds.

 

[pattismith]

@Gemini
I put the doc with the full paper in this message.

I wonder if any Fibro patient ever improved with a treatment meant to cure auto-immune disorder...

 

[Inara]

This is highly interesting. Thanks for posting it @Gemini! So there still is some biomed research in Fibromyalgia - good to see.

 

[Gemini]

@GeminiI wonder if any Fibro patient ever improve with a treatment meant to cure auto-immune disorder...

Good question @pattismith.

Bevan presented a list of those treatments including Rituximab in his talk:

Last Item on Andersson's Conclusion chart ">Novel Mechanism-based therapies" is interesting.

Thank you for the full paper.

 

[Gemini]

So there still is some biomed research in Fibromyalgia - good to see.

Agree it is good to see @Inara.

I almost overlooked Andersson's presentation but became curious when Dr. Fluge referred to it.

I'm hoping NIH's Vicky Whittemore takes word of it back to her Institute NINDS, responsible for a large "Pain Initiative," and that she'll help in any way she can Andersson run ME/CFS IgG through his experiment...

 

[Sidny]

and when antibodies are removed pain subsides. A diagnostic test and specific FM treatments that deplete antibodies, for example, could follow.

Our results demonstrate that fibromyalgia pain is caused by IgG autoantibodies that sensitize peripheral nociceptive afferents neurons and suggest that therapies that reduce patient IgG titres may be effective treatments of fibromyalgia pain.

I think the idea that lowering IGGs (the immune response) is flawed especially if you’re in the camp that believes ME\CFS and Fibromyalgia are the result of persistent infection in tissues.

Dr. Skip Prigden posits Fibro is the result of chronic HSV infection (IMO probably other HHVs working synergistically to create misery)Dr. Micheal VanElzakker proposes a similar theory that chronic HHV infection of the vagus nerve and brain stem is inducing sickness behavior. Similarly enteroviruses have been found in the muscles and central nervous system tissue of ME/CFS patients.

Doesn’t seem like very much of a stretch to suppose our immune systems are producing antibodies to these invaders and their associated proteins/metabolites.

I doubt the body is aberrantly producing IGGs that cause the pain and fatigue in ME\CFS and Fibro as they likely serve to keep any number of intracellular pathogens from exploding out of control (albeit at the cost of our quality of life)

These findings are interesting but I think researchers need to look further upstream from IGG response and attempt to eradicate what’s driving it (ie chronic infections) and the ensuing host cell metabolism disruptions they cause.