14 replies to this topic

[ioanna]

Given the huge body of research focused on the correlation between the incidence of viruses and bacteria, on the one hand, and autoimmunity, on the other, should we maybe reconsider the 'auto' in autoimmunity? Is autoimmunity a more sophisticated and poorly understood form of a normal human immune response, facilitated by a certain genetic configuration? It is true that autoimmunity targets self antigens, but it is equally true that infectious organisms can alter these self antigens. I have given a lot of thought to this question and I even wrote a post about it on my blog, Mauve, which I have registered on Longecity some time ago. http://mauveornot.bl...toimmunity.html I appreciate your input!

[Antonio2014]

That some autoinmune diseases are caused by viruses doesn't mean that all autoinmune diseases are caused by viruses. Also, it doesn't mean that they are not autoinmune and are more like infections. Also, some cancers are caused by viruses and still we call them cancers, not infections. If it walks like a duck, quacks like a duck and looks like a duck, we call it a duck.

[xEva]

I have been interested in this issue for a long time. ..though it's complicated by doctors' tendency to diagnose 'autoimmunity' when they cannot find the pathogen that drives inflammation and other symptoms of disease. Such was my personal experience. For many years I had an illusive chronic infection that no tests could reveal. Various MDs on both sides of the Atlantic kept telling me that mine was an 'autoimmune condition' and that I would have to learn to live with it. By chance, a week-long course of antibiotics cured me once and for all. After that I can't help wondering how many people are similarly misdiagnosed. Does autoimmunity really exist? It makes no sense from evolutionary perspective. 

[smccomas01]

XEva if you do not mind what antibiotic were you treated with? 

[Danail Bulgaria]

It will be best to identify the microbe, make it an antibiogram, and target it with several powerful antibiotics, that affect it the best.

By the way, there is a theory, in the official medicine, that microorganisms change the DNA, and cause autoimune reaction.

[smccomas01]

I found this not to long ago concerning both Crohn's and RA. The drug they are trialing is really a combination of 3 different antibiotics. The drug used to be called Myoconda.    

 

http://www.redhillbi...peline/rhb-104/

 

 

Edited by smccomas01, 11 November 2014 - 02:21 PM.

[chubtoad]

Take a mouse breed genetically predisposed to an autoimmune disease, and raise it in sterile environment.  Will it still get the disease?

Edited by chubtoad, 11 November 2014 - 08:18 PM.

[xEva]

Take a mouse breed genetically predisposed to an autoimmune disease, and raise it in sterile environment.  Will it still get the disease?

 

 

The whole proposition is doubtful. Is there an animal "genetically predisposed"  to an autoimmune disease? Aberrant genes that would make the immune sys attack the host should be weeded out of population in no time. 

[smccomas01]

I tend to agree with xEva on this. 

[corb]

in no time.

 

You should consider the "no time" on an evolutionary scale.
And I'd like to point out, when it comes to a disease like type 1 diabetes which is in no way detrimental to procreation the whole "it's gonna get weeded out" is kinda ... baseless. Why would it get weeded out? How?

[xEva]

You should consider the "no time" on an evolutionary scale.
And I'd like to point out, when it comes to a disease like type 1 diabetes which is in no way detrimental to procreation the whole "it's gonna get weeded out" is kinda ... baseless. Why would it get weeded out? How?

Well, according to Infectious causation of disease: An evolutionary perspective (Ewald and Cochran, 2000), "no time" comes to about 3 generations (-? citing from memory). ..yeah, surprisingly short time.

Regarding type 1 diabetes, in my understanding, this is not a "genetic disease" but the consequence of an infection, to which the immune sys overreacts and destroys beta-cells in the process. Why such overreaction is genetically preserved? Because, in most cases, vigorous response to an infection is beneficial to an organism.

[corb]

Why such overreaction is genetically preserved?

 

Because it doesn't result in spontaneous abortion or extremely early death universally.

From a pure evolutionary standpoint there is little natural selection can do, let alone in 3 generations , to tackle this combination of mutations. I already pointed out - it doesn't impair procreation - the parents can have more kids, healthy kids, which inherit some of the mutated genes, and even worse in the case of late onset type 1, the person with the genetic disorder will have kids of his own pretty much guaranteeing the mutations carry on.

 

So in the case of diabetes 3 to 10 generations mentioned in your paper won't be enough to effect any change. In fact we have written records of diabetes from 1000s BC so it's a genetic disorder that's been around for a while. And killed a lot of kids in the process.

 

But I guess your main point is any of these genes in their mutated form could be beneficial so they persist in populations, which is not untrue entirely they were beneficial at one time to become widespread enough, but I'd like to point out again from the standpoint of evolution a disease has to be incredibility widespread like malaria - for a genetic changed to be pushed into the population. Diseases like that were rare historically so it's not plausible to expect every mutation causing autoimmunity was caused by an overreaction to an infectious agent. So again I'll use diabetes as an example as far as we know the mutations for diabetes were caused by climate change, which explains why diabetes causing genes have perceived with a greater frequency in the northern hemisphere .

 

And to finish, any genetics paper which supposedly accounts for admixture - but doesn't say HOW - is not a paper I would quote. Genetic drift is quite faster than natural selection in some cases, that's the only thing we can get out of that paper.

[xEva]

@corb: I don't quite follow you. The mutations that carry on aid survival, like is the case with malaria and sickle cell disease. A carrier of a mutated gene is not quite susceptible to malaria, but a child that inherits both mutated copies is unlikely to procreate. This is a famous example of how aberrant genes carry on.

Re type 1 diabetes, I don't consider it a genetic disorder. What evidence you have for it? I'm aware that that's what people thought about it not that long ago, but that's the point already made in this thread: whenever the infectious agent cannot be identified, it's called 'autoimmune disease'.


'autoimmunity' was a buzzword for the last 50 years or so. But before that, for the most of the 20th century, most diseases were caused by 'nerves' and 'stress', like for example gastric ulcers. And so the patients were advised to minimize their stress and improve their diet, and when it did not help had parts of their stomachs cut out. Then an Australian discovered that ulcers were caused by a common bacterium. Now the patients are treated with antibiotics. But it's the same disease, and it's been the same for millenia. Only our understanding of it changed.

Edited by xEva, 21 November 2014 - 07:26 AM.

[corb]

I'm aware that that's what people thought about it not that long ago, but that's the point already made in this thread: whenever the infectious agent cannot be identified, it's called 'autoimmune disease'.

And by not long ago you mean right now.

Type 1 diabetes is still considered a genetic disorder.

Is researched as a genetic disorder. And is treated as a genetic disorder. With success.

The problem with you xEva is you take an exception and you make it a rule.

 

 

@corb: I don't quite follow you. The mutations that carry on aid survival,

Aided survival in most cases. They are not something that has come about in 3 generations, most of these mutations take thousands of years to develop and by the time they are widespread there is not much that can replace them in the gene pool. Which is how they remain in circulation long after they have become useless or detrimental. Especially in the case of T1D, which can develop in childhood but ALSO in adulthood by the time most people have already procreated so the genetic mutations that cause it not only get passed around in semi safe form one by one but also as the full autoimmune disease causing package. It simply isn't detrimental enough to get removed from the genepool in a timely manner and now that we can treat it to a degree, it will remain in the gene pool for even longer.

 

In the case of the sickle cell from the paper you posted they were investigating populations which were mixed with other genepools for centuries, and still the disease remained. So you can see, it's not THAT easy to get rid of a mutation once it's become widespread enough.

[smccomas01]

"The problem with you xEva is you take an exception and you make it a rule"

If I understand the intent of the post xEva is saying the opposite. The rule being if the cause of a condition is unknown the condition gets thrown into the autoimmune bucket. Now there is evidence that the some of the diseases are not autoimmune, the body is actually fighting or dealing with a type of infection.

 

Example Crohn's is considered an autoimmune disease there is a company called redhill biopharma they are currently in phase 3 trial of a drug RHB-104 for Crohn's. This drug used to be called Myoconda RedHill purchased it from Giaconda Ltd.

 

Prior to this there were trials of Myconda  and the results were " remission rate of 65% with a clinical response of almost 95%. These results exceed those of any Crohn’s therapy on the market by major margins."

 

Myoconda is a combination of 3 different Antibiotics  rifabutin, clarithromycin and clofazimine. The hypothesis is that Crohn's is caused by a MAP infection and these 3 antibiotics are used to treat those type of infections.

 

The point I am getting at is I agree with the original post and xEva we need to rethink the "auto" in autoimmune disease.

 

You can read more about Myoconda here

 

http://lifescientist...ease-1137126586