Autoimmune theory of disease

Autoimmune diseases are thought to arise from an overactive immune response of the body against substances and tissues normally present in the body. The autoimmune disease theory has yet to present a satisfactory reason, evolutionary or otherwise, why an immune system would attack human tissue.

Conversely, the Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop. explains that so-called “autoantibodies” are merely antibodies generated in response to pathogenic bacterial cells that have been destroyed as a result of an active immune response.

At least forty different chronic diseases are suspected or accepted as being caused by an autoimmune response.

A number of theories attempt to explain why antibodies are present in certain diseases, why the body might attack itself:

• Clonal Anergy theory
• Idiotype Network theory
• Clonal Ignorance theory
• Suppressor population theory
• Clonal Deletion theory

The last of these theories was first proposed by the 1960 Nobel laureate in medicine, Frank M. Burnett, some fifty years ago. The variety and age of these theories suggests how wide open the field is and has been.

According to many doctors and researchers, the best way to treat an overreactive immune response is to suppress it. To that end, many patients with autoimmune diseases are given regular doses of corticosteroids, anti-TNF drugs, and others, which profoundly modulate a body's immune response.

In some cases, patients may experience temporary symptom relief lasting months or even years. Yet, immunomodulatory drugs have a number of liabilities.

• range of negative side effects
• there is no proof of long-term survival benefit from use
• some drugs have been shown to cause relapse
• practice guidelines advocate moderate dosing

Also, if autoimmunity were causing disease, wouldn't disrupting molecular mechanisms put a stop to autoimmune disease? Shouldn't corticosteroidsA first-line treatment for a number of diseases. Corticosteroids work by slowing the innate immune response. This provides some patients with temporary symptom palliation but exacerbates the disease over the long-term by allowing chronic pathogens to proliferate. and anti-TNF drugsDrugs which interfere with the body's production of TNF-alpha - a cytokine necessary for recovery from infection cure a patient of autoimmune disease?

If anything, patients with autoimmune disease are immunocompromised. A study of the prevalence of the key antimicrobial peptide showed that patients with sarcoidosis expressed it less than healthy subjects, and that sicker sarcoidosis patients expressed it least of all. Source: Kanchwala et al.

There are a number of reasons why the autoimmune theory of disease is likely wrong:

• Autoimmune patients show signs of being immunocompromised. For example, Kanchwala et al. showed that patients with sarcoidosis expressed the antimicrobial peptide cathelicidin Family of antimicrobial peptides found primarily in immune cells and transcribed by the Vitamin D Receptor. less than healthy subjects, and that sicker sarcoidosis patients expressed it least of all.¹
• The advent of novel molecular sequencing tools is showing how many pathogenic bacteria are missed using traditional techniques. It is no longer necessary to grow fastidious bacteria in vitroA technique of performing a given procedure in a controlled environment outside of a living organism - usually a laboratory. – that is, in a Petri dish – in order to prove they are present in the human body.
• A number of autoimmune disease have all the hallmarks of infection including granuloma, inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue., unique microbe populations, and co-infections.
• Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. patients' immunopathological response to low-dose antibiotics and a Vitamin D Receptor agonistA substance such as olmesartan (Benicar) or 1,25-D which activates the Vitamin D Receptor and transcribes the genes necessary for a proper innate immune response. is also highly suggestive of a bacterial pathogenesis.
• Organs and tissue from sarcoidosis patients have been shown to cause sarcoidosis in the transplanted recipients strongly suggesting that autoimmune diseases are transmissible. This is supported by the strong aggregation of chronic diseases in communities and families.
• Patients with autoimmune disease often show inconsistent signs of autoimmune reactivity:

The interesting thing was that sarcoidosis there are usually no antibodies. There is usually a very low sedimentation rate indicating that there's no real obvious pathogens, the immune system is not feeling anything. And that's one of the reasons it's such an idiopathic and has been such a puzzling disease.

Yet, when you look at the malaise suffered by the patients, the malaise is a straight line. There is no peaking of the malaise that was coincident with the peaking of the antibodies. In fact, the antibodies just seem to be bystanders, if you like, of the main disease process.

Trevor Marshall, PhD, 2006 Bio21 presentation

A number of evolutionary biologists have taken exception to the theory of autoimmunity based on what they know about how species change over time. According to evolutionary theory, there is no way that genes that determine a person will get an autoimmune disease will stay in a population for long. The forces of reproductive fitness are simply too strong.

One thing that we clearly know causes inflammation is the presence of an infection. So, as soon as I hear the word inflammation I think, “What infectious agents are at play?”

That brings us to the concept of autoimmune disease – the idea that the immune system just “goes crazy.” I think the fact that the concept of autoimmunity was developed in the first place is largely related to the fact that our brains have not evolved to think scientifically. People who have studied disease from their own point of view have recognized that the immune system is extremely important. But as we’ve learned more about the immune system, we’ve realized that it is an extremely complicated system - as complicated as the brain. Just like we can’t look at one type of neuron and infer information about the entire brain, we can’t try to understand the characteristics of only some immune cells and think we understand immune function.

So, over the years, as researchers have been daunted by the complexity of the immune system, it has seemed logical that such a complex entity has the potential to go wrong. Because they are limited by the power of their brains, they tend to simplify the issue and view the immune system in the same way they would view a truck that could break down. There are two problems with this type of thinking. For starters, we can’t trust our intuition that something complex is likely to malfunction. The fact is, the immune system functions just fine in a large proportion of the population. The only logical way to explain the immune activation seen in patients with “autoimmune disease” is to suggest that there is some sort of agent pushing the immune system off balance. This argument is only strengthened by the fact that the same evolutionary forces that would cause a serious disease to be weeded from the population would also cause those people whose immune systems are prone to self-destruction to be eliminated from the population.

The concept of autoimmune disease has progressed to the point that now even researchers who previously dismissed the possibility of infection are accepting the possibility that “autoimmune” disease could be triggered by infection. This is some progress, but it’s not enough. Especially since the concept of autoimmunity encourages doctors to prescribe immunosuppressive steroids to patients. But if persistent infection is involved these steroids may exacerbate the fire by allowing pathogens to spread.

Paul Ewald, Baceriality.com

To think that autoimmune disease is caused by an interaction between the environment and human genetics, as a number of commentators have, is only marginally more plausible. Evolutionary theory is clear that any kind of consistent reproductive disadvantage is consistently and ultimately weeded out of the population.

Auto-antibodies, antibodies directed at the self, do exist and have been documented – but growing evidence suggests they don't cause autoimmune illnesses.

How then does one account for why these proteins are observed in patients with “autoimmune disease”? Is there a true target?

During Th1 infection, I am sure that science will eventually be able to find the true targets of these, and that they will be pathogen-related, not self-related.

Paul Ewald, Baceriality.com

According to Trevor Marshall, autoantibodies are “incidental roadkill.” Intraphagocytic pathogens do damage via the innate immune system functions which they directly compromise, and auto-antibodies are a byproduct of the cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. and chemokine cascade which ensues.

It is quite plausible that “autoimmunity” is also caused by bacterial-induced alteration of human genes. All a bacterium would need to do in order to generate an apparent “autoimmune” reaction would be to interfere with the genes necessary for the production of proteins against which autoantibodies are produced.

According to one analysis, 463 human genes are changed during an infection with Mycobacterium tuberculosis.² These mutated genes function in various cellular processes including intracellular signalling, cytoskeletal rearrangement, apoptosis, transcriptional regulation, cell surface receptors, cell-mediated immunity and cellular metabolic pathways.

There's no reason to think that other bacteria can do just as much damage – or that any pathogenic bacteria, for that matter, can interfere with production of autoantibodies.