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+ | ====== Presentation - Antibodies and infection in the era of metagenome ====== | ||
+ | **Type:** Conference presentation\\ | ||
+ | **Presenter: | ||
+ | **Conference: | ||
+ | **Location: | ||
+ | **Date: | ||
+ | **See also:** [[http:// | ||
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+ | |||
+ | {{ vimeo> | ||
+ | |||
+ | |||
+ | ===== Transcript ===== | ||
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+ | So far at this conference we've heard some amazing work which shows how individual pathogens cause human disease. | ||
+ | |||
+ | Researchers running the initiative estimate that 90% of cells in the human body are bacterial, fungal or otherwise non-human in origin while a mere 10% of cells in Homo Sapiens are truly human. | ||
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+ | It follows that humans are best viewed as superorganisms. | ||
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+ | For example, this slide represents the bacteria recently determined to persist in saliva by researchers at the Max Planck Institute. | ||
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+ | When it comes to the human microbiota, medicine is now comfortable that bacterial populations exist in the gut and areas of the body in contact with the external environment, | ||
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+ | This chart shows the bacterial species detected when scientists at the University of Glasgow sequenced the bacteria in biofilm removed from prosthetic hip joints during revision arthroplasties - joints that were removed from a body compartment thought to be sterile. | ||
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+ | Components of such a metagenomic microbiota can persist in the cytoplasm of the very cells of the immune system that are supposed to kill them, in biofilm communities in which they are protected from the immune response by a self-created polymeric matrix. I'm about to show you a clip of bacteria in the blood of a patient with Chronic Fatigue Syndrome, taken by Dr. Andy Wright of Manchester, UK. It is fresh blood that has been aged for around 6 hours at the time of the video. | ||
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+ | So how does this microbiota persist? | ||
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+ | A fully activated immune response should be capable of clearing pathogens from the body. So it's not surprising that many pathogens have evolved mechanisms that allow them to slow the innate immune response in order to enhance their survival. | ||
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+ | The TACO gene, when expressed, inhibits mycobacterial entry as well as survival. | ||
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+ | The VDR expresses at least 913 genes, many connected to autoimmune conditions and cancers. | ||
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+ | We have shown that at least one bacterial metabolite produced by biofilm bacteria also slows activity of the VDR. | ||
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+ | Here is a molecular emulation of the ligand, the sulphonolipid Capnine, sitting in the VDR binding pocket - obstructing other ligands that would otherwise activate the receptor from docking and initiating gene transcription.n | ||
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+ | Slowing the ability of the VDR to produce the AMPs and TLR2 is such a logical survival mechanism for any form of pathogen that its almost certain that other microbes besides Mtb and HIV have also evolved ways to dyregulate the VDR or the other receptors involved in controlling the innate immune response. | ||
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+ | So it appears that the microbiota responsible for autoimmune disease gradually shuts down the innate immune response over a person' | ||
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+ | In essence, wear and tear aside, as the microbiota accumulates over a lifetime, humans go from this...to this. | ||
+ | We have been running a large observational trial for patients with various autoimmune diagnoses that uses a VDR agonist to restart the VDR nuclear receptor and very low dose bacteriostatic antibiotics to help eliminate the microbiota. | ||
+ | |||
+ | The goal of the treatment is bacterial death. | ||
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+ | While not all patients on the MP have been on the treatment long enough to report symptomatic resolution, nearly all the patients who have started the treatment have experienced immunopathology. | ||
+ | But what causes the antibodies? | ||
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+ | Patient A is a 58 year old female who was diagnosed with RA in 1996. She started the MP in August of 2004. | ||
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+ | Also, as reported via an online progress report, patient A noted a steady decrease in her RA symptoms during and after the same period that her ANA test results became negative. | ||
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+ | Patient A's test results and reaction to the MP again support the hypothesis that RA and other autoimmune disease result from the accumulation of a pathogenic microbiota. | ||
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+ | This calls for a re-evaluation of the ' | ||
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+ | Here's another case history. | ||
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+ | Another 55-year-old female patient was diagnosed with Hashimoto' | ||
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+ | Note that the antibody titers of patients A, B and C actually went up from their baseline level during early periods of treatment with the MP. These early periods of treatment corresponded to times when each patient reported high levels of immunopathology, | ||
+ | | ||
+ | A shift in the way we understand the production of antibodies in autoimmune disease would, of course, change the way such diseases are treated. If we accept that the antibodies observed in diseases like RA, lupus and others are created in response to bacterial death, then treating patients with corticosteroids to slow the immune response is counterproductive and is likely to exacerbate the disease process by allowing pathogens to spread. | ||
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+ | Instead, if the antibodies in autoimmune disease are created largely in response to bacteria, | ||
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+ | Robert Koch theorized that one pathogen causes one disease. | ||
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+ | Our own data confirms this overlap. | ||
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+ | This may explain why we also see so much overlap between antibody production in patients with different autoimmune diagnoses and why such antibodies are often polyspecific. | ||
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+ | The key point to take home from this presentation is to understand that the microbiota can persist by suppressing the innate immune system. | ||
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+ | < | ||
+ | ===== Questions and answers ===== | ||
+ | |||
+ | **Question: | ||
+ | |||
+ | **Answer:** ... | ||
+ | --></ |