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Saturday, 9 August 2014

Autoimmune diseases - the friendly fire of our immune system

Autoimmune diseases affect millions of people, and have become an important focus of scientific research in the past decade due to their apparent increase in prevalence worldwide[1][2] - and yet little is known about their cause. Our body’s immune system is a pathogen-fighting machine, finely adapted to seek and destroy any foreign invaders which might cause damage within our bodies. To do this, it needs to be able to work out what is dangerous foreign material and what isn't, and sometimes it can get confused. Common allergies like hay fever occur when the body treats harmless pollen like a dangerous pathogen, and mounts an immune response. This can be irritating, but the real problem comes when your immune system becomes convinced your own body is a danger, and begins attacking itself. This is what happens in autoimmune diseases

The precise cause of these diseases is unknown but is thought to be a combination of both genetic and environmental factors[3]. It is known that relatives of people with autoimmune diseases are more likely to develop them, yet multiple studies have shown that in a pair of identical twins, with identical sets of genes[4], sometimes only one twin will develop an autoimmune disease.

This suggests that while genetic factors can predispose you to an illness, an environmental factor may be involved in triggering the development of the disease. One type of environmental factor associated with autoimmunity is infection. Exposure to numerous common viruses has been described as a risk factor for developing autoimmunity. A well-known example is the Epstein-Barr virus (EBV) which is the cause of glandular fever (also known as the ‘kissing disease’ or Infectious Mononucleosis). Over 90% of the adult population are latently infected with EBV, meaning the virus is present in their system but does not cause any symptoms.

Electron microscopic image of two Epstein Barr Virus virions
All viruses have the ability to evade the host’s immune system in some way - this ability to hide from the immune system enables viruses to survive. Immune suppressive responses have evolved in viruses over time, and they have even stolen bits of our immune system that are beneficial to them. Image credit: By Liza Gross[8] ©2005 Public Library of Science (CC-BY).

Just like any other virus, the EBV virus is able to evade its host’s immune system. One way it does this is to produce proteins which modulate the host’s immune system. In the majority of people this has no detrimental effect; however in people with genetic susceptibility to autoimmunity an immune response to the body's own tissues is initiated. We have not yet been able to explain why it affects this small proportion of people, but not the many others also infected.

The options available for treating autoimmune diseases were previously limited to very basic therapies. These included injecting gold salts to reduce inflammation in rheumatoid arthritis. While in many cases we still don’t understand why they work, these types of treatments are rarely used now due to their multiple side effects.

The introduction of biologic therapies using drugs which target molecules involved in the functioning of the immune system has revolutionised therapy and improved many patients’ lives dramatically. One example of these are monoclonal antibodies, such as Anti-TNF. Monoclonal antibodies recognise and latch on to specific proteins on the surface of cells, so can be made to target whatever cells are needed for the therapy to work. Anti-TNF targets TNF, a chemical produced by the immune system which triggers inflammation. In some types of autoimmune disease, it isn’t properly regulated, leading to damaging levels of inflammation. Antibody therapy can help to reduce this inflammation, and so improve the patient’s symptoms.

Photograph of male rheumatoid arthritis sufferer
One example of the basic therapies for autoimmune diseases which we used to rely on is the use of injected gold salts for the treatment of rheumatoid arthritis, although we don’t understand why this works.  In previous years patients were not started on therapy until joint damage was detected.[7] Image credit:Photograph © handarmdoc (CC-BY)

Although they are often effective, a significant proportion of patients do not respond well to these drugs[5][6], and we still don’t fully know why this is the case. Much research is being done on developing biomarkers of diseases that will help not only detect the disease in the first instance, but also predict response to therapy. What is known, however, is that early diagnosis of disease is a good predictor of disease response - patients in the early stages of disease tend to respond better. The aim is that eventually, a blood test will reveal the best treatment regime for each individual patient.

Even for patients who do show positive responses to treatment, there are still a number of drawbacks - the drugs are extremely expensive and the majority require administration by intravenous drips. This makes it inconvenient to the patient and requires a trained professional to administer the drugs. The fact that these drugs modify and/or suppress the immune system means they can leave individuals susceptible to infections. Some people may also develop an allergic reaction to the drug.

Autoimmune diseases are both fascinating and heartbreaking. The immune system is one of the most impressive aspects of the human anatomy, and it's a truly terrible thing for a person's own body to turn against them. We still need more details about what is going on in a patient's body to understand and how and why these conditions arise and why viruses affect some people but not others. Hopefully a better understanding will allow the development of more universally effective treatments with fewer side effects.

This article was written by Ellen Margaret Moran - a researcher currently based in Perth, Western Australia. Ellen carried out her PhD in Rheumatology and has worked in medical research since completion. Ellen is a writer and editor with Bitesize Bio and tweets at @EllenMoran83

References
why don't all references have links?

[1] Shapira Y, Agmon-Levin N, Shoenfeld Y. "Defining and analyzing geoepidemiology and human autoimmunity." Journal of Autoimmunity. 2010 May;34(3):J168-77. doi: 10.1016/j.jaut.2009.11.018. Epub 2010 Jan 19. Review. PubMed PMID: 20034761.

[2] Rook GA, Lowry CA, Raison CL. "Microbial 'Old Friends', immunoregulation and stress resilience." Evolution, Medicine, and Public Health. 2013 Jan;2013(1):46-64. doi: 10.1093/emph/eot004. Epub 2013 Apr 9. PubMed PMID: 24481186; PubMed Central PMCID: PMC3868387.

[3] Vojdani A. "A Potential Link between Environmental Triggers and Autoimmunity." Autoimmune Diseases. 2014;2014:437231. doi: 10.1155/2014/437231. Epub 2014 Feb 12. Review. PubMed PMID: 24688790; PubMed Central PMCID: PMC3945069.

[4] Bogdanos DP, Smyk DS, Rigopoulou EI, Mytilinaiou MG, Heneghan MA, Selmi C, Gershwin ME. "Twin studies in autoimmune disease: genetics, gender and environment." Journal of Autoimmunity. 2012 May;38(2-3):J156-69. doi: 10.1016/j.jaut.2011.11.003. Epub 2011 Dec 15. Review. PubMed PMID: 22177232.

[5] Rendas-Baum R, Wallenstein GV, Koncz T, Kosinski M, Yang M, Bradley J, Zwillich SH. "Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors." Arthritis Research & Therapy. 2011 Feb 16;13(1):R25. doi: 10.1186/ar3249. PubMed PMID: 21324169; PubMed Central PMCID: PMC3241369.

[6] Sfikakis PP, Tsokos GC. "Towards the next generation of anti-TNF drugs." Clinical Immunology. 2011 Dec;141(3):231-5. doi: 10.1016/j.clim.2011.09.005. Epub 2011 Sep 16. PubMed PMID: 22004846.

[7] Bresnihan B. "Rheumatoid arthritis: principles of early treatment." The Journal of Rheumatology. 2002;29 Suppl 66:9-12. Review. PubMed PMID: 12435163. Quinn MA, Emery P. Are early arthritis clinics necessary? Best Pract Res Clin Rheumatol. 2005 Feb;19(1):1-17. Review. PubMed PMID: 15588968.

[8] Gros L. "Virus Proteins Prevent Cell Suicide Long Enough to Establish Latent Infection." PLoS Biol 3(12): e430. doi:10.1371/journal.pbio.0030430