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Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after HPV vaccine

pattismith

Senior Member
Messages
3,931
What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in
Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus (HPV) Vaccination?


Varvara A. Ryabkova 1, Leonid P. Churilov 1,2 and Yehuda Shoenfeld 1,3, *
1Laboratory of the Mosaic of Autoimmunity, Saint Petersburg State University, Saint-Petersburg 199034,
Russian Federation; varvara-ryabkova@yandex.ru (V.A.R.); elpach@mail.ru (L.P.C.)
2Saint Petersburg Research Institute of Phthisiopulmonology; Saint-Petersburg 191036, Russian Federation
3Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, affiliated to Tel-Aviv University
School of Medicine, Tel-Hashomer 52621, Israel

Published: 18 October 2019
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Abstract:
Fibromyalgia is a disorder characterized by chronic widespread pain and non-pain
symptoms, such as fatigue, dysautonomia, and cognitive and sleep disturbances. Its pathogenesis and treatment continue to be the subject of debate. We highlight the role of three mechanisms—autoimmunity, neuroinflammation, and small fiber neuropathy—in the pathogenesis of the disease.

These mechanisms are shown to be closely interlinked (also on a molecular level), and the review considers the implementation of this relationship in the search for therapeutic options.

We also pay attention to chronic fatigue syndrome, which overlaps with fibromyalgia, and propose a concept of “autoimmune hypothalamopathy” for its pathogenesis.

Finally, we analyze the molecular mechanisms underlying the neuroinflammatory background in the development of adverse events following HPV vaccination and suggesting neuroinflammation, which could exacerbate the development of symptoms following HPV vaccination (though this is hotly debated), as a model for fibromyalgia pathogenesis.
 

pattismith

Senior Member
Messages
3,931
"53% of individuals who reported a chronic disease after vaccination against HPV met the diagnostic criteria for FM [97]. It is important to indicate that, as a reaction to independent publications of case series with similar symptoms following HPV vaccination by authors from Denmark [94] and Japan [95], international health authorities provided several studies on the issue.

The European Medicines Agency judged that there was no relationship between the vaccine against
HPV and the development of complex regional pain syndrome or postural orthostatic tachycardia [98].

Reviews conducted by British, [99] Canadian [100], and Spanish [101] health authorities supported
the safety of immunization against HPV. A powerful argument put forward by the defenders of this
vaccine was that the large, double-blind, randomized preclinical studies guaranteed the safety of the
HPV vaccine [102]. These randomized studies have a higher level of reliability in evidence-based
scientific medicine and eliminate cases that are not related to vaccination itself. The results are totally
independent of the judgment of the researchers.

However, a critical review of randomized trials and post-marketing case series has also been published [103]. It was suggested by Martínez-Lavn [102] that if the veracity of the complex of symptoms following HPV vaccination in genetically prone individuals is corroborated, it could become a model of FM pathogenesis. The author speculated that SFN and dysautonomia could be the key mechanisms underlying both these conditions. There are grounds for this conclusion. (1)

In two different studies, SFN was detected in 17/40 and 20/40 patients with neurologic symptoms following HPV vaccination [95,96]. (2)
In those patients who met the criteria for FM, there was a correlation between the severity of FM, as measured by ACR-2010, and the intensity of dysautonomia scored by the composite autonomic symptom score (COMPASS-31).
Dysautonomia following HPV vaccination could be a result of the autoimmune process. AAb against different G-protein coupled receptors was looked for in the sera of adolescent girls (n=55) with symptoms of prolonged general fatigue, orthostatic intolerance, chronic regional pain syndrome, and cognitive
dysfunction following HPV vaccination [92]. The serum levels of AAb against α1 AR, α2 AR, β1 AR,
β2 AR, M1 AChR, M2 AChR, M3 AChR, M4 AChR, M5 AChR, and the endothelin receptor were found
to be significantly elevated in the vaccinated girls compared with the controls [92]."
 

pattismith

Senior Member
Messages
3,931
"Although acute disseminated encephalomyelitis, myelitis, optic neuritis, multiple sclerosis, and encephalitis were reported following HPV vaccination , no significant association was found between central demyelination, multiple sclerosis, optic neuritis, and HPV vaccination. However, cognitive and neurological symptoms are an inherent part of the adverse events reported following HPV vaccination. There are data suggesting that autoimmune encephalitis could be underappreciated in reports on post-HPV vaccination phenomena.

In one study, 71% of patients with neurological symptoms, which developed following HPV vaccination,
demonstrated an autoimmune encephalitis pattern in the 123-I-IMP-SPECT study.

Some of them had AAb against ganglionic AChR or gangliosides, while about half of the patients responded well to repeating immune adsorption plasmapheresis under steroids and azathioprine.

Besides vaccine antigens, which could cause (due to the molecular mimicry phenomenon) the development of
AAb targeting the central nervous system, the second component of HPV vaccines—aluminum adjuvants—could also induce a neuroinflammatory background in patients who develop adverse events following HPV vaccination.
Signs of an inflammatory process in the CNS and the toxicity of Al adjuvant/Al-containing vaccines has been reported in different countries and in both mouse and large animal (sheep) models. "
 

ryan31337

Senior Member
Messages
664
Location
South East, England
Despite a focus on HPV vaccination, this paper starts by proposing more general, joined-up thinking surrounding the pathogenesis of FM and CFS. From the paper:
1572872656788.png


Can't comment on the accuracy but they seem to be hitting a lot of the big talking points at the moment. A number of factors promoting autoimmunity, which in turn drives SFN & mito dysfunction, all of which contribute to neuroinflammation. They consider CFS distinct from FM in respect of the former having specific autoimmune hypothalamus involvement. They also consider FM (and presumably CFS in some cases) as potentially being subclinical manifestations of better known autoimmune diseases.
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in
Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus (HPV) Vaccination?


we analyze the molecular mechanisms underlying the neuroinflammatory background in the development of adverse events following HPV vaccination and suggesting neuroinflammation

See Mehlsen's HPV vaccine study from this year's London Conference:

https://forums.phoenixrising.me/threads/dr-mehlsens-study-me-cfs-following-hpv-vaccination.77275/
 

pattismith

Senior Member
Messages
3,931

pattismith

Senior Member
Messages
3,931
Coexistence of cerebral hypometabolism and neuroinflammation in the thalamo-limbic-brainstem region in young women with functional somatic syndrome
Takashi Matsudaira 1 2, Tatsuhiro Terada 1 2, Tomokazu Obi 2, Masamichi Yokokura 3, Yukitoshi Takahashi 4, Yasuomi Ouchi 5
Free PMC article
Abstract
Background:
Functional somatic syndrome (FSS) is a disorder characterized by clusters of medically unexplained symptoms.
Some women suffer from persistent FSS after human papillomavirus (HPV) vaccination.
However, a causal relationship has not been established, and the pathophysiology of FSS remains elusive.

Here, we aimed to identify the brain regions showing altered cerebral metabolism and neuroinflammation in patients with FSS and to correlate the measures of positron emission tomography (PET) with clinical data.

Twelve women diagnosed with FSS following HPV vaccination (FSS group) underwent both [18F]FDG-PET to measure glucose metabolism and [11C]DPA713-PET to measure neuroinflammation.

[18F]FDG standardized uptake value ratio (SUVR) and [11C]DPA713 binding potential (BPND) values were compared voxel-wise between the FSS and control groups (n = 12 for [18F]FDG, n = 16 for [11C]DPA713).

A region-of-interest (ROI)-based analysis was performed to correlate PET parameters with clinical scores. Statistical significance was set at p < 0.05 corrected for multiple comparisons.


Results:

Statistical parametric mapping revealed a concomitant significant decrease of [18F]FDG SUVR (glucose metabolixm) and increase of [11C]DPA713 BPND (neuroinflammation) in the regions covering the thalamus, mesial temporal area, and brainstem in the FSS group.

Correlation analysis revealed that intelligence and memory scores were significantly positively correlated with [18F]FDG SUVR (glucose metabolism) and negatively so with [11C]DPA713 BPND (neuroinflammation) in these regions.

A direct comparison between [18F]FDG SUVR and [11C]DPA713 BPND revealed a significant positive correlation in the right hippocampus and amygdala.


Conclusions:

Cerebral hypometabolism with neuroinflammation occurring in the thalamo-limbic-brainstem region may reflect the pathophysiology of FSS.
 

pattismith

Senior Member
Messages
3,931
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) demonstrates distinct autoimmune and autoinflammatory disease associations according to the adjuvant subtype: Insights from an analysis of 500 cases
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https://doi.org/10.1016/j.clim.2019.03.007Get rights and content

Abstract

Background
We investigated the pattern of reported immune diseases in the international ASIA syndrome registry.

Methods
Data from 500 subjects exposed to adjuvants from the ASIA syndrome international registry were analysed.

Results
The patient mean age was 43 ± 17 years and 89% were female.

Within the reported immune diseases, 69% were well-defined immune diseases (autoimmune, autoinflammation, and mixed pattern diseases).

Among the well-defined immune diseases following the exposure to adjuvants, polygenic autoimmune diseases were significantly higher than autoinflammatory disorders (92.7% vs 5.8%, respectively, p < 0.001).

Polygenic autoimmune diseases such as connective tissue diseases were significantly linked to the exposure to HBV vaccine (OR 3.15 [95%CI 1.08–9.23], p = 0.036).

Polygenic autoinflammatory diseases were significantly associated with the exposure to influenza vaccination (OR 10.98 [95%CI 3.81–31.67], p < 0.0001).

Conclusions
Immune conditions following vaccination are rare, and among these, polygenic autoimmune diseases represent the vast majority of the well-defined immune diseases reported under the umbrella ASIA syndrome. However, vaccines benefit outweighs their autoimmune side effects.


Hereditary Autoinflammatory syndromes, formerly known as periodic fever syndromes, are a heterogeneous and ever increasing group of rare inflammatory disorders that manifest with recurrent fevers and/or inflammatory episodes (see Table 41.5). Recurrent fevers or inflammation can often be mistaken for recurrent infections.

Patients exhibit characteristic physical findings during these episodes, such as fever, various rashes, lymphadenopathy, aphthous stomatitis, arthritis, and serositis with abdominal, chest, or testicular pain.

These episodes can be periodic or sporadic, but the characteristic features occur with each episode. Laboratory evaluation may show elevated white blood cell (WBC) counts and elevated inflammatory markers during the episode that typically resolve between episodes. Importantly, infectious work-ups are often repeatedly negative, and the patient is typically well between febrile episodes.

There are also an increasing number of disorders of immune dysregulation that have been described (Table 41.6).

Unlike autoinflammatory disorders, these disorders result in a failure to control T and B cell responses, resulting in autoimmunity.

These disorders are not typically episodic, and once autoimmunity develops it continues until treated. Many of these disorders are also associated with immune deficiency and recurrent infection, thus patients experience recurrent infections simultaneously with autoimmune manifestations.
Autoinflammatory Disease - an overview | ScienceDirect Topics

Some diseases are mixed autoimmune/autoinflammatory like Psoriasis. (psoriasis can show up or flare after some flu vaccine)