Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

Dow, Coad Thomas

doi:10.3390/microorganisms8020212

Cited by 17 publications

(21 citation statements)

References 158 publications

(173 reference statements)

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“…paratuberculosis (MAP) in AD [31]. It is notable that the ongoing BCG clinical trials for autoimmune diabetes and multiple sclerosis are both diseases associated with MAP [32].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

et al. 2022

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BCG vaccine has been used for 100 years to prevent tuberculosis. Not all countries, including the United States, adopted the initial World Health Organization recommendation to use BCG. Moreover, many Western countries that had routinely used BCG have discontinued its use. Recent population studies demonstrate lower prevalence of Alzheimer’s disease (AD) in countries with high BCG coverage. Intravesicular instillation of BCG is also used to treat bladder cancer that has not invaded the bladder muscle wall and has been shown to reduce recurrence. Several retrospective studies of bladder cancer patients demonstrated that BCG treatment was associated with a significantly reduced risk of developing AD. Plasma amyloid β assessment has become a fertile area of study for an AD biomarker that is predictive of a positive amyloid PET scan. Mass spectrometry-based plasma amyloid 42/40 ratio has proven to be accurate and robust, and when combined with age and ApoE, is shown to accurately predict current and future brain amyloid status. These parameters, amyloid 42/40 ratio, age and ApoE genotype are incorporated into an Amyloid Probability Score (APS)–a score that identifies low, intermediate or high risk of having a PET scan positive for cerebral amyloid. Community recruitment was used for this open-label pilot study. Forty-nine BCG-naïve, immunocompetent individuals completed our study: prior to BCG prime and boost, as determined by the APS, 34 had low risk (APS 0–35), 5 had intermediate risk (APS 36–57) and 10 had high risk (APS 58–100). The APS range for the participant group was 0 to 94. Follow-up plasma amyloid testing 9 months after vaccination revealed a reduction in the APS in all the risk groups: low risk group (p = 0. 37), intermediate risk group (p = 0.13) and the high-risk group (statistically significant, p = 0.016). Greater benefit was seen in younger participants and those with the highest risk. The small number of participants and the nascent status of plasma amyloid testing will rightfully temper embracement of these results. However, both the favorable direction of change after BCG as well as the utility of the APS—a valuable surrogate AD biomarker—may prompt a definitive large-scale multicenter investigation of BCG and AD risk as determined by plasma amyloid peptide ratios and APS.

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“…paratuberculosis (MAP) in AD [31]. It is notable that the ongoing BCG clinical trials for autoimmune diabetes and multiple sclerosis are both diseases associated with MAP [32].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

et al. 2022

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“…BCG vaccine achieves this effect by inducing pattern recognition receptor NOD2, resulting in metabolic changes with epigenetic rewiring [5]. The reasoning behind the initiating of this process is immunomodulation [6]. This immune-modulatory mechanism of BCG was reported to limit the progression of autoimmune Type 1 Diabetes Mellitus (T1D) and Multiple sclerosis (MS).…”

Section: Introductionmentioning

confidence: 99%

Avoiding COVID-19 Complications with Diabetic Patients Could Be Achieved by Multi-Dose Bacillus Calmette–Guérin Vaccine: A Case Study of Beta Cells Regeneration by Serendipity

Ayoub¹,

Ramadan²,

Ashoush³

et al. 2020

Preprint

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Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c &/or irregular blood glucose levels. Diabetic patient’s mortality rates with COVID-19 are higher than cardiovascular or cancer patients. Recently Bacillus Calmette–Guérin (BCG) has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to Beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from TB and leprosy and has been repositioned for treatment of bladder cancer, diabetes & multiple sclerosis. Recently, the COVID-19 epidemiological study confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 & diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide & PCPRI laboratory findings after BCG vaccination for a 9 years’ patient. The patient was re-vaccinated based on a negative tuberculin test & no scar at the site of injection of the 1st BCG vaccination at birth. Furthermore, the authors in the present article described a prospective BCG multi-dose clinical study in full details that they will apply in case of acceptance of their submitted grant & the ethical committee approval. The aim of the clinical study is to check if double dose BCG (4 weeks apart) will show a significant difference in the protection of health care professionals in Egypt. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions & exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.

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“…In the past 10 years, clinical trials of adult BCG vaccination have shown therapeutic benefits for an array of disease – including a variety of allergic and autoimmune disease such as type 1 diabetes mellitus and multiple sclerosis [ [83] , [84] , [85] , [86] , [87] , [88] , [89] , [90] , [91] ]. Hence, we have hypothesized that BCG may help ameliorate the development of other autoimmune diseases that have been linked to mycobacteria [ 92 ]. Shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

What is the evidence that mycobacteria are associated with the pathogenesis of Sjogren’s syndrome?

Dow

Chan

2021

Journal of Translational Autoimmunity

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Sjogren’s syndrome (SS) is a common, systemic autoimmune disorder primarily affecting the exocrine glands resulting in xerostomia and xerophthalmia. SS may also manifest with polyarthralgia, polyarthritis, polymyalgia, cutaneous/other organ vasculitis, interstitial lung disease, and/or various other disorders. The primary autoantibodies associated with SS and used as adjuncts to diagnosis are anti-Ro (SSA) and anti-La (SSB). The pathogenesis of SS is considered to involve genetic susceptibility and environmental triggers. An identified genetic susceptibility for SS lies in variants of the tumor necrosis factor alpha inducible protein 3 ( TNFAIP3 ) gene, the product of which is known as A20. Deficiency or dysfunction of A20 is known to induce macrophage inflammatory response to mycobacteria, potentially increasing the repertoire of mycobacterial antigens available and predisposing to autoimmunity via the paradigm of molecular mimicry; i.e. , providing a mechanistic link between genetic susceptibility to SS and exposure to environmental non-tuberculous mycobacteria (NTM). Mycobacterium avium ss. paratuberculosis ( MAP ) is an NTM that causes Johne’s disease, an enteritis of ruminant animals. Humans are broadly exposed to MAP or its antigens in the environment and in food products from infected animals. MAP has also been implicated as an environmental trigger for a number of autoimmune diseases via cross reactivity of its heat shock protein 65 (hsp65) with host-specific proteins. In the context of SS, mycobacterial hsp65 shares epitope homology with the Ro and La proteins. A recent study showed a strong association between SS and antibodies to mycobacterial hsp65. If and when this association is validated, it would be important to determine whether bacillus Calmette-Guerin (BCG) vaccination (known to be protective against NTM likely through epigenetic alteration of innate and adaptive immunity) and anti-mycobacterial drugs (to decrease mycobacterial antigenic load) may have a preventive or therapeutic role against SS. Evidence to support this concept is that BCG has shown benefit in type 1 diabetes mellitus and multiple sclerosis, autoimmune diseases that have been linked to MAP via hsp65 and disease-specific autoantibodies. In conclusion, a number of factors lend credence to the notion of a pathogenic link between environmental mycobacteria and SS, including the presence of antibodies to mycobacterial hsp65 in SS, the homology of hsp65 with SS autoantigens, and the beneficial effects seen with BCG vaccination against certain autoimmune diseases. Furthermore, given that BCG may protect against NTM, has immune modifying effects, and has a strong safety record of billions of doses given, BCG and/or anti-mycobacterial therapeutics should be studied in SS.

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Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

Cited by 17 publications

References 158 publications

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

Avoiding COVID-19 Complications with Diabetic Patients Could Be Achieved by Multi-Dose Bacillus Calmette–Guérin Vaccine: A Case Study of Beta Cells Regeneration by Serendipity

What is the evidence that mycobacteria are associated with the pathogenesis of Sjogren’s syndrome?

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Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

Cited by 17 publications

References 158 publications

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

Avoiding COVID-19 Complications with Diabetic Patients Could Be Achieved by Multi-Dose Bacillus Calmette&ndash;Gu&eacute;rin Vaccine: A Case Study of Beta Cells Regeneration by Serendipity

What is the evidence that mycobacteria are associated with the pathogenesis of Sjogren’s syndrome?

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Resources

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Avoiding COVID-19 Complications with Diabetic Patients Could Be Achieved by Multi-Dose Bacillus Calmette–Guérin Vaccine: A Case Study of Beta Cells Regeneration by Serendipity