Causes of Rheumatoid Arthritis
If you’ve been suffering with the pain, stiffness, and fatigue of rheumatoid arthritis (RA), you may often ask yourself, “Why me?” It seems so mysterious why some people develop RA and others don’t.
RA is an autoimmune disease in which the body’s immune system attacks synovial membranes. These membranes surround joints. As they are attacked, they thicken with inflammation. The process begins to destroy cartilage and bone inside the joint. But what is the trigger that causes the immune system to attack its own body?
The answer is complex and not yet fully understood, involving genes and environmental factors.
Known Risk Factors
Genes and environmental risks combine to create the risk for RA.
According to a study in Arthritis and Rheumatism, about 40 percent of RA risk comes from an inherited tendency. Certain genes linked to a protein called the Human Leukocyte Antigen can make RA more of a risk. The “Shared Epitope”, or SE, gene is one most strongly linked with RA risk.
Certain behaviors, such as smoking, make RA more likely. The combination of smoking and having certain genes like the SE gene make RA more likely, and more aggressive when it does occur. Smoking creates certain chemicals with citrullination. These chemicals occur much more often in those with RA, and they may be part of a process that triggers RA.
Other Risk Factors
Obesity increases the likelihood of developing RA. One study found a possible link between an increase in population obesity and rising cases of RA.
Women are two to three times more likely to get RA than men. According to the Centers for Disease Control, hormones may play a role in RA risk in women.
Certain infections may trigger the onset of a faulty immune system, but nothing has yet been conclusively identified.
According to the National Institutes of Health, insecticide use may raise the risk of RA. Other chemical exposures like traffic pollution, hairspray, and lipstick might have chemicals that can cause an increased risk.
Markers of Risk
Changes in an RA sufferer’s immune system can occur years before symptoms develop. Certain markers in the blood have been found to indicate the potential for disease. Not all people with RA have these markers, but many do.
Rheumatoid Factor (RF) is an antibody. Abnormally high levels of RF are sometimes detected in people with autoimmune diseases, including rheumatoid arthritis, Sjogren’s Syndrome, and systemic lupus erythematosis. However, some people with high levels of RF do not have these diseases.
According to one study, Anti-CCP antibodies are more specific for diagnosing RA than the RF antibody. It may also better predict the severity of the disease. Anti-CCP may be detected years before the onset of disease.
Immune System Basics
Your immune system is a complicated system involving dozens of different kinds of cells. A complex set of genes helps your cells recognize and attack foreign invaders. There are many different kinds of white blood cells (WBC) and important proteins that help recognize and protect against certain foreign (“not self”) chemicals.
In an autoimmune disease, WBCs react to proteins that are supposed to be in your body (“self” proteins). This causes the cells to attack some part of the body.
More Immune System Function
The important protein for RA is the Human Leukocyte Antigen, or HLA. This protein works to “present” chopped up bits of cells and viruses. There are several kinds, some that occur on the surface of all cells in the body, and some which are on “professional” presenting cells – certain special kinds of WBCs.
HLAs have a very complex gene structure that can actually create thousands of slightly different HLA proteins. This variation allows the body to detect a lot more potential threats.
When HLA Goes Bad
In some people with RA, the HLA system creates HLA proteins that react to proteins inside the synovial membrane of joints. The HLA proteins present these “self” proteins in a way that excites T cells, a type of WBC. When T cells are activated, the body mounts an attack on the “invader”, causing inflammation and damage at the site of the attack.
Some people have HLA genes that make this process more likely. Others may be exposed to environmental factors that increase their risk. Some RA patients may actually have both genetic and environmental triggers.
What This Means
Understanding how RA is triggered is still evolving. Many ongoing studies are looking at how to predict who may be at increased risk of developing RA. Understanding how RA is triggered may also help to better treat RA and prevent the progression of the disease. Biologic medicines like infliximab, adalimumab, etanercept, and golimumab have been developed to interfere with the inflammatory processes that attack joints. But these treatments have side effects that can lead to severe infections.
As more understanding of RA triggers develops, new treatments may arise that can more specifically reduce RA symptoms while maintaining the immune system’s ability to fight real invading organisms.
- Arthritis: Environmental Exposure to Hairspray, Lipstick, Pollution Can Trigger Autoimmune Diseases. (January 27, 2010) Science News. Retrieved September 26, 2013 from http://www.sciencedaily.com/releases/2010/01/100125123231.htm
- Can Smoking Trigger Autoimmunity in RA? (2013) The Arthritis Foundation. Retrieved September 25, 2013 from http://www.arthritistoday.org/about-arthritis/types-of-arthritis/rheumatoid-arthritis/who-gets-ra-and-why/causes-of-rheumatoid-arthritis/ra-and-smoking-2.php
- Crowson, C et al. (2013) Contribution of obesity to the rise in incidence of rheumatoid arthritis. Arthritis Care and Research. 65(1):71-77. Retrieved September 26, 2013 from http://onlinelibrary.wiley.com/doi/10.1002/acr.21660/abstract
- Disorders of the Immune System. (2008) National Institute of Allergy and Infectious Diseases. Retrieved September 26, 2013 from http://www.niaid.nih.gov/topics/immunesystem/Pages/disorders.aspx
- Ehrman, J. (2011) Pesticide Use Linked to Lupus, Rheumatoid Arthritis. NIH Record, Vol LXIII No. 6. Retrieved September 26, 2013 from http://nihrecord.od.nih.gov/newsletters/2011/03_18_2011/story4.htm
- Frisell, T et al. (2013) Familial risks and heritability of RA in relation to RF/ACPA status, number and type of affected relatives, sex and age. Arthritis and Rheumatism. 10.1002/art.38097. Retrieved September 25, 2013 from http://onlinelibrary.wiley.com/doi/10.1002/art.38097/abstract
- Hart, J et al. (2009) Exposure to Pollution and Increased Risk of Rheumatoid Arthritis. Environ Health Perspectives. 117(7): 1065-1069. Retrieved September 26, 2013 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717131/
- Janeway, CA et al. (2001) The major histocompatibility complex and its functions. In: Immunobiology: The Immune System in Health and Disease. New York, Garland Science. Retrieved September 25, 2013 from http://www.ncbi.nlm.nih.gov/books/NBK27156/
- Keyser, F. (2011) Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspective. Curr Rheumatol Rev. 7(1): 77-87. Retrieved September 26, 2013 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182090/
- Nishimura, K et al. (2007) Meta-analysis: Diagnostic Accuracy of Anti-Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis. Ann Intern Med. 146(11): 797-808. Retrieved September 26, 2013 from http://annals.org/article.aspx?articleid=734878
- Obesity May Be a Risk Factor for Developing RA. (2013) The Arthritis Foundation. Retrieved September 25, 2013 from http://www.arthritistoday.org/news/obesity-rheumatoid-arthritis-risk194.php
- Rheumatoid Arthritis. (November 2012) Centers for Disease Control. Retrieved September 26, 2013 from http://www.cdc.gov/arthritis/basics/rheumatoid.htm
- Rheumatoid Arthritis. (2013) The Mayo Clinic. Retrieved September 25, 2013 from http://www.mayoclinic.com/health/rheumatoid-arthritis/DS00020/DSECTION=risk-factors
- Rheumatoid Factor. (2011) Medline Plus. Retrieved September 26, 2013 from http://www.nlm.nih.gov/medlineplus/ency/article/003548.htm
- What Causes Rheumatoid Arthritis? (2013) The Arthritis Foundation. Retrieved September 25, 2013 from http://www.arthritistoday.org/about-arthritis/types-of-arthritis/rheumatoid-arthritis/who-gets-ra-and-why/causes-of-rheumatoid-arthritis/what-causes-ra.php