Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses

Abstract:

(1) Background: Macrophagic myofasciitis (MMF) is an inflammatory histopathological lesion demonstrating long-term biopersistence of vaccine-derived aluminum adjuvants within muscular phagocytic cells. Affected patients suffer from widespread myalgia and severe fatigue consistent with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a poorly understood disorder suspected to result from chronic immune stimulation by infectious and inorganic particles.

(2) Methods: In this study we determined the immuno-metabolic properties of MMF phagocytic cells compared to controls, at rest and upon exposure to aluminum oxyhydroxide adjuvant, with or without adsorbed antigens, using protein quantification and an oxygen consumption assay.

(3) Results: MMF and control cells similarly internalized the adjuvant and vaccine but MMF cells specifically expressed Rubicon and Nox2, two molecules unique to the LC3-associated phagocytosis (LAP) machinery, a non-canonical autophagic pathway able to downregulate canonical autophagy. MMF cells exhibited an altered inflammatory secretome, producing more pain-inducing CXC chemokines and less TNF-α than controls, consistent with chronic myalgia and exhaustion of the immune system previously documented in ME/CFS. MMF cells exhibited mitochondrial metabolism dysfunction, with exacerbated reaction to adjuvanted vaccine, contrasting with limited spare respiratory capacity and marked proton leak weakening energy production.

(4) Conclusions: MMF phagocytes seemingly use LAP to handle aluminum oxyhydroxide vaccine particles, secrete pain-inducing molecules, and exhibit exacerbated metabolic reaction to the vaccine with limited capacity to respond to ongoing energetic requests.

Source: Masson JD, Badran G, Gherardi RK, Authier FJ, Crépeaux G. Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses. Toxics. 2024 Jul 4;12(7):491. doi: 10.3390/toxics12070491. PMID: 39058143. https://www.mdpi.com/2305-6304/12/7/491 (Full text)

Vaccine-Related Chronic Fatigue Syndrome In An Individual Demonstrating Aluminium Overload

A team of scientists have investigated a case of vaccine-associated chronic fatigue syndrome (CFS) and macrophagic myofasciitis in an individual demonstrating aluminium overload.

This is the first report linking aluminium overload with either of the two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in a patient.

The team, led by Dr Chris Exley, of the Birchall Centre at Keele University in Staffordshire, UK, has found a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events that are associated with autoimmune conditions, including chronic fatigue syndrome and macrophagic myofasciitis.

The CFS in a 43-year-old man, with no history of previous illness, followed a course of five vaccinations, each of which included an aluminium-based adjuvant. The latter are extremely effective immunogens in their own right and so improve the immune response to whichever antigen is administered in their presence. While the course of vaccinations was cited by an industrial injuries tribunal as the cause of the CFS in the individual, it was not likely to be a cause of the elevated body burden of aluminium. The latter was probably ongoing at the time when the vaccinations were administered and it is proposed that the cause of the CFS in this individual was a heightened immune response, initially to the aluminium in each of the adjuvants and thereafter spreading to other significant body stores of aluminium.

The result was a severe and ongoing immune response to elevated body stores of aluminium, which was initiated by a course of five aluminium adjuvant-based vaccinations within a short period of time. There are strong precedents for delayed hypersensitivity to aluminium in children receiving vaccinations which include aluminium-based adjuvants, with as many as 1% of recipients showing such a response.

While the use of aluminium-based adjuvants may be safe, it is also possible that for a significant number of individuals they may represent a significant health risk, such as was found in this case. With this in mind the ongoing programme of mass vaccination of young women in the UK against the human papilloma virus (HPV) with a vaccine which uses an aluminium based adjuvant may not be without similar risks.

Recent press coverage of myalgic encephalomyelitis (ME) or chronic fatigue syndrome has highlighted the potentially debilitating nature of this disease and related conditions. The cause of CFS is unknown.

 

Source: Keele University. (2008, November 18). Vaccine-Related Chronic Fatigue Syndrome In An Individual Demonstrating Aluminium Overload. ScienceDaily. Retrieved March 4, 2017 from  https://www.sciencedaily.com/releases/2008/11/081118141856.htm

 

A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.

Abstract:

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

 

Source: Exley C, Swarbrick L, Gherardi RK, Authier FJ. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Med Hypotheses. 2009 Feb;72(2):135-9. doi: 10.1016/j.mehy.2008.09.040. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19004564

 

Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome

Abstract:

Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001. Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries. The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients.

One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis.

Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy. Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile.

It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome. Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms.

Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome. Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis. Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome.

Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide.

 

Source: Gherardi RK. Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome. Rev Neurol (Paris). 2003 Feb;159(2):162-4. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/12660567

 

Chronic fatigue syndrome in patients with macrophagic myofasciitis

Macrophagic myofasciitis (MMF), a condition first reported in France in 1998, is defined by the presence of a stereotyped and immunologically active lesion at deltoid muscle biopsy . It was recently demonstrated that this lesion is an indicator of long-term persistence of the immunologic adjuvant aluminum hydroxide within the cytoplasm of macrophages at the site of previous intramuscular (IM) injection. MMF is typically detected in patients with diffuse arthromyalgias that have appeared subsequent to aluminum hydroxide administration in the absence of a clearly defined anatomic substratum. Patients also report unexplained chronic fatigue. These manifestations are reminiscent of the so-called chronic fatigue syndrome (CFS), a poorly understood condition manifesting as disabling fatigue, musculoskeletal pain, sleep disturbance, impaired concentration, and headaches. The present study was conducted to determine the proportion of MMF patients fulfilling international criteria for CFS.

You can read the rest of this article here: http://onlinelibrary.wiley.com/doi/10.1002/art.10740/full

 

Source: Authier FJ, Sauvat S, Champey J, Drogou I, Coquet M, Gherardi RK. Chronic fatigue syndrome in patients with macrophagic myofasciitis. Arthritis Rheum. 2003 Feb;48(2):569-70. http://onlinelibrary.wiley.com/doi/10.1002/art.10740/full (Full article)