JUST TO PROVOKE THOUGHT!
With all the diseases in our world, we tend to focus on the name vs the mechanism and seeing the connection of placement. placement of two different categories, the AutoImmune and AutoInflammatory
Years after years the question is where do these diseases stem from? Are they Genetic, infectious, environmental, are they caused by T-cells, Nfkappa B, over production vs underproduction of immunes response…to what? Theories? VS Facts..
I will identify our two Diseases and conclude with my WHY.
Autoimmune disorders are conditions that occur when the immune system mistakenly attacks and destroys healthy body tissue. MedLine Plus suggests that there are “ more than 80 different types of autoimmune disorders”. With the thought process of their being two diseases one AutoImmune and other AutoInflammatory, I would add that their are a lot more than 80 known AID(AutoImmune Diseases)
Our white blood cells are supposed to help protect the body from harmful substances, called antigens. Antigens include bacteria, viruses,cancer cells, toxins and blood or tissues from another person or species. The immune system produces antibodies that destroy these harmful substances.
Those diagnosed with an autoimmune disorder, have an immune system that can’t tell the difference between healthy body tissue and antigens.
Auto inflammatory diseases arise from disorders with the innate immune system. We have the adaptive immune system which selectively targets and fights infectious agents using antibodies. Then we have the innate immune system which fights anything in the body that it recognizes as foreign or non-self with a general and immediate response. Autoimmune and inflammatory both involve the adaptive immune system. The hallmark for innate immunity is inflammation.
“Autoimmune and Autoinflammatory diseases share common characteristics in that both groups of disorders result from the immune system attacking the body’s own tissues, and also result in increased inflammation.
So, now you have a basic idea of AutoInflammatory vs. Autoimmune Diseases. All known Diseases fall under one of these two “LABELS”. Although, each can show a genetic predisposition and or a trigger such as environmental exposure, the question still remains what is the CAUSE.
Lets think common sense vs. EGO. Ego in this realm referring to what we have been told, what is theoretical. The answer is the GUT bacteria. The question then is asked what about those born with a disease that haven’t had anything by mouth or haven’t been exposed? The answer is we since conception are exposed. The flora of the mothers gut is passed a long to the egg, the nutrients, exposures are also passed on to the child. We are learning about the sperm of others staying in the woman’s body which can also contribute to the toxic mix. What we know is
“The human body carries about 100 trillion microorganisms in its intestines a number ten times greater than the total number of human cells in the body.The metabolic activities performed by these bacteria resemble those of an organ, leading some to liken gut bacteria to a “forgotten” organ. It is estimated that these gut flora have around a hundred times as many genes in aggregate as there are in the human genome . Bacteria make up most of the flora in the colon and up to 60% of the dry mass of feces. Somewhere between 300 and 1000 different species live in the gut, with most estimates at about 500. However, it is probable that 99% of the bacteria come from about 30 or 40 species. Fungi and protozoa also make up a part of the gut flora, but little is known about their activities” Wikipedia
Lets take Multiple sclerosis as an example, which I have always believed to be an AutoInflammatory Disease
“it is apparently not harmful bacteria that trigger multiple sclerosis, but beneficial ones – specifically, the natural intestinal flora, which every human being needs for digestion. The researchers discovered that genetically modified mice develop an inflammation in the brain similar to the human disease if they have normal bacterial intestinal flora. The microorganisms begin by activating the immune system’s T cells and, in a further step, the B immune cells. The findings suggest that in humans with the corresponding genetic predisposition, the essentially beneficial intestinal flora could act as a trigger for the development of multiple sclerosis”.Max Planck Institute of Neurobiology
This astonishing finding was made possible by newly developed genetically modified mice. In the absence of exposure to any external influences, inflammatory reactions arise in the brains of these animals which are similar to those associated with multiple sclerosis in humans – however, this only occurs when the mice have intact intestinal flora. Mice without microorganisms in their intestines and held in a sterile environment remained healthy. When the scientists “vaccinated” the animals raised in sterile conditions with normal intestinal microorganisms, they also became ill.
Conclusion: All diseases can fall under one of two labels. They can be AutoImmune or AutoInflammatory, this said it is the inflammation in both diseases that kill, cause the most damage. I understand that genetic and the environment play a significant role in the trigger to activate a disease.
“However, could it be that the gut bacteria influence how diseases occur and what form they take? Physicians and scientists should focus on disrupting these gut-immune pathways to understand the impact of gut flora activity on activity of autoimmune and autoinflammatory conditions”
Influence of diseases are environmental and genetics, caused by Gut bacteria~~ lisa Moreno~Dickinson
Some new facts are relevant here
Females are affected by all autoimmune diseases almost 10/1 compared to males. So obesity, Diabetes, Lupus, Rheumatoid arthritis, Allergic Rhinits, and Asthma, IBS, Crohns Disease, and Colitis, also predominate in females. A recent study published in Science discussesed this gender bias in mice and found the gut bacteria either made estrogens (female) or androgens (male ) hormones. If one transferred the gut flora from mice genetically predisposed to Obesity and Diabetes (NOD 2 mice) to lean mice they became obese. This suggested the gut flora are the environmnetal effecors of autoimmunity in all of these autoimmune diseases where some genetic predispositon prevails. Thus Lupus used to be associated with the DR 2 and DR3 loci of genetic susceptibility. At last count over 30 different susceptibility genes have been documented. But if a disease is entirely genetic one would expect that all genetically predisposed would succumb to it. Not so as identical twins with Lupus have a concordance rate of not 100% But around 40%. This suggests the environment plays a larger role than previously contemplated.
What is in the environment affecting genes?
Bacteria in the gut are either Pathogens -cause disease, or Commensals which protect -sustain health and wellness and prevent disease.
Adaptive Immune responses are driven by Effector – T cells and B cells. The full understanding of the nature of this commensalism is still not in. What we do know is that many of the pathogenic bacteria have de-methylated DNA as their antigenic stimulus to activate effector T and B cells. Human DNA we have found is either non antigenic or poorly antigenic in humans. We also found that it has a paucity of CpG motifs which are methylated and it activates not the Effector T cells which are activated by de-methyalted DNA but the Suppressor/Regulator potpulation of T cells now called T Regs. Arising from this data we have developed a synthetic DNA vaccine which is patent protected to Up-regulate these TRegs in all of these dsiease cited above. Data already published by others has shown that TRegs are deficient in all of these autoimmune diseases.
These fndings suggest that Lupus as an example is an Epi -Genetic disease. This defines that the basic DNA sequence is not altered but the outside of the gene is. Epi means -On. Methylation means a CH3 methyl group is appended to the outside of the base pairs namely A for adenine T for thymine C for cytosine and G for guanine. While all of these 4 base pairs can be methylated the most frequent and therefore functional, are the C and G and often described as the CpG motifs.We are now asking the questions like What is the % of CpGs present in commensals versus pathogens. It varies between 27-57% What % are methylated No data is avilable yet.But some important new findings are pushing us forward .
How does this help in CAIDS or autoinflammtion. It works as the body has a limited no of avenues which cause Inflammation. We therfore talk about Pathways of inflammation such as the Jak Stat, NFkappa B, and the Inflammasomal pathways. It has been recently shown that activated TRegs block or suppress almost all ot these pathways. It is the Inflammasomal pathway which is most pertinent to both the Autoinflammatory and Alzheimers diseases. So we are pursuing methods of upregulating T Regs and modulating them by hormone,s Vitamin D, ACTH, bromocriptine to blockProlactin, and all other means to maximize their effectiveness in these diseases.~ Dr. Lawless