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home:publications:proal_autoimmunity_2010 [06.15.2010] – marysuehome:publications:proal_autoimmunity_2010 [06.15.2010] – marysue
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 Take, for example, the Vitamin D Receptor or VDR - it's a type 1 nuclear receptor. Well, it turns out that viruses like Epstein-Barr Virus and bacteria like //Mycobacterium tuberculosis// have evolved to survive in the same fashion - and that's by slowing activity of the VDR.(({{pubmed>long:19550398}}))  For example, MTb downregulates VDR activity by about a factor of 3.3.  And, this slide shows VDR activity being downregulated actually, by almost a factor of 30 in the longer lasting cell lines of B cells infected with EBV.  Take, for example, the Vitamin D Receptor or VDR - it's a type 1 nuclear receptor. Well, it turns out that viruses like Epstein-Barr Virus and bacteria like //Mycobacterium tuberculosis// have evolved to survive in the same fashion - and that's by slowing activity of the VDR.(({{pubmed>long:19550398}}))  For example, MTb downregulates VDR activity by about a factor of 3.3.  And, this slide shows VDR activity being downregulated actually, by almost a factor of 30 in the longer lasting cell lines of B cells infected with EBV. 
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 ====#9 The Vitamin D Receptor (VDR)==== ====#9 The Vitamin D Receptor (VDR)====
  
-Why the VDR? Well, colloquially speaking, the VDR serves as a "gatekeeper" to the innate immune response - So, it expresses Cathelecidin, it expresses these key endogenous antimicrobials, that the body needs to actually target these intracellular pathogens. - Cathelecidin - the beta-Defensins - it also expresses Toll-like receptor 2. In addition to that, it expresses at least 913 genes, many connected to autoimmune diseases and cancers. So by dysregulating and slowing the VDR, Epstein-Barr Virus and Mycobacterium tuberculosis have actually evolved to slow the body's very defense mechanisms that would otherwise be actively working to render them dead.+So, basically - you might ask, why the VDR? Well, colloquially speaking, the VDR serves as a "gatekeeper" to the innate immune response - So, it expresses Cathelecidin, it expresses these key endogenous antimicrobials, that the body needs in order to target intracellular pathogens.  Cathelecidin - the beta-Defensins - it also expresses Toll-like receptor 2. In addition to that, it expresses at least 913 genes, many connected to autoimmune diseases and cancers. So, by dysregulating and slowing the VDR, Epstein-Barr Virus and Mycobacterium tuberculosis have actually evolved to slow the body's very defense mechanisms that would otherwise be actively working to render them dead.
 ====#10 HIV and Borrelia burgdorferi==== ====#10 HIV and Borrelia burgdorferi====
  
-Note that HIV persists in the same fashion. It completely overtakes the VDR in order to transcribe its own genome.(({{pubmed>long:17556530}})) And, //Borrelia// (Bb) does as well.  Live Borrelia downregulates the receptor by about a factor of 50, lysed by a factor of 8.(({{pubmed>long:19461888}}))+And note that HIV persists in the same fashion. It completely overtakes the VDR in order to transcribe its own genome.(({{pubmed>long:17556530}})) And, //Borrelia// (Bb) does as well.  Live Borrelia downregulates the receptor by about a factor of 50, lysed by about a factor of 8.(({{pubmed>long:19461888}}))
  
-This is such a logical survival mechanism on the part of these microbes that it is almost certain other less well-studied microbes have also evolved to slow VDR activity, or the activity of other receptors involved in controlling the immune response.+So - this is such a logical survival mechanism on the part of these microbes that it's almost certain that other less well-studied microbes have also evolved to slow VDR activity, or the activity of other receptors involved in controlling the immune response.
 ====#11 Successive infection==== ====#11 Successive infection====
  
-Well, these persistence mechanisms result in a snowball effect. When the immune system slows, and a person acquires one pathogen, then it becomes easier to acquire another pathogen.  Then the immune system acquires another pathogen.  These pathogens - they can each slow the immune system in turn. They can be viral, bacterial, fungal... and so on and so on. And this process is referred to as successive infection.+Well, these persistence mechanisms result in a snowball effect. When the immune system slows, and a person acquires one pathogen, then it becomes easier for them to acquire yet another pathogen.  And the immune system then acquires yet another pathogen.  And these pathogens each slow the immune system in turn. And the pathogens - they can be viral, fungal, bacterial... and so on and so on. And this process is referred to as successive infection.
  
 In the context of successive infection, an inflammatory disease state appears to result from the combined pathogenicity of the sum of microbes that any one person accumulates over the course of a lifetime. As human genes are upregulated or downregulated by components of these microbes, the human body shifts further and further away from its natural state of homeostasis. In the context of successive infection, an inflammatory disease state appears to result from the combined pathogenicity of the sum of microbes that any one person accumulates over the course of a lifetime. As human genes are upregulated or downregulated by components of these microbes, the human body shifts further and further away from its natural state of homeostasis.
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 ====#12 Epstein-Barr Virus (EBV)==== ====#12 Epstein-Barr Virus (EBV)====
  
-So, for example, over the past years, Epstein-Barr Virus has been detected in so many different proportions in so many disease states.  Here's just a sample of conditions associated with EBV. For almost the last century, these results have served as the source of such confusion.  But, if we view them through the lens of metagenomics and in the context of successive infection they make sense! Epstein-Barr Virus is just one component of a mix. In some cases it could be a precipitating factor for an autoimmune disease. Or, in other cases, it's just a pathogen that is acquired later on in the disease process, when the body's already dealing with the widespread immunsuppression that can be caused by the hundreds of bacterial pathogens that accumulate in the body. And we now understand that by altering nuclear receptor activity, viruses can aid the survival of bacteria and vice versa. +So, for example, over the past years, Epstein-Barr Virus has been detected in so many different proportions in so many disease states.  Here's just a sample of different diseases that've been associated with EBV. And for almost the last century, these results have served as the source of confusion.  But, if we view them through the lens of metagenomics and in the context of successive infection they make sense! Epstein-Barr Virus is just one component of a mix. In some cases it could be a precipitating factor for an autoimmune disease condition. Or, in other cases, it's just a pathogen that's acquired later on in the disease process, when the body's already dealing with the widespread immunsuppression that can be caused by any of the hundreds of bacterial pathogens that accumulate in the body. And we now understand that by altering nuclear receptor activity, viruses can aid the survival of bacteria and vice versa. 
 ====#13 Pathogens, aka "rascals"==== ====#13 Pathogens, aka "rascals"====
  
-With this in mind, a "one microbe/one disease" paradigm is no longer viable and treatments for autoimmune disease that aim to eradicate only a single microbe - such as say, our purple friend here (EBV) - will at best succeed in only reversing a very small part of the overall disease process.+With this in mind, a "one microbe/one disease" paradigm is no longer viable and treatments for autoimmune disease that aim to eradicate only a single microbe - let's say, only our purple friend here (EBV) - will at best succeed in only reversing a very small part of the overall disease process.
 ====#14 Co-morbidities among inflammatory diagnoses==== ====#14 Co-morbidities among inflammatory diagnoses====
  
-Well, it may also not be by accident that the uniqueness with which a patients' autoimmune disease symptoms develop parallels the incredible diversity of the pathogens that can persist in the human body. The following wheel shows how truly related chronic diseases are. Each “spoke” on the wheel represents a published study that's shown a significant statistical relationship between patients suffering from one disease and the next. And that is a lot of comorbidity and a lot of symptom overlap.+Well, it may also not be by accident that the uniqueness with which a patients' autoimmune symptoms develop parallels the incredible diversity of the pathogens that can persist in the human body. The following wheel shows how truly related chronic diseases are. Each “spoke” on the wheel represents a published study that's shown a significant statistical relationship between patients suffering from one disease and the next. And that is a lot of comorbidity and a lot of symptom overlap. 
 ====#15 Select bacterial genera detected in commonly smoked cigarettes==== ====#15 Select bacterial genera detected in commonly smoked cigarettes====
  
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