YOUR OWN WORST ENEMY:
A Summary of Lupus
Editor's Note: Spurred by a fascination with autoimmunity, Lily C. ('15) chose to research lupus for her final paper during her AP Biology Class' unit on the immune system.
Introduction
The human immune system is meant to protect us from and attack foreign invaders (known as pathogens), such as influenza viruses or the bacteria that cause tuberculosis. In some cases, however, the immune system attacks normal components of the individual’s own body, such as the myelin sheath of neurons (in the condition multiple sclerosis) or the insulin producing cells of the pancreas (this is the suspected cause of type I diabetes). Systemic Lupus Erythematosus (SLE) is a chronic, potentially life threatening autoimmune condition that can affect any part of the body, causing inflammation. SLE accounts for ~70% of all lupus cases.
There are three other types of lupus: cutaneous, drug-induced, and neonatal. However, these types are relatively uncommon and, generally, less serious. Cutaneous lupus is limited to problems involving the skin, such as rashes. Drug-induced lupus has symptoms similar to SLE, but often goes away months after the offending medication is stopped. Neonatal lupus rarely occurs in newborn children of women with lupus, and the effects usually disappear within a few months.
Lupus, particularly SLE, can have a devastating impact on patients. The disease can interfere with the function of major organs, causing complications such as kidney failure and heart attacks. Daily symptoms, which may include skin problems and joint pain, can have a significant negative impact on functioning and quality of life.
Causes of Lupus
As with many autoimmune disorders, there is still a lot to be discovered about the causes of lupus. Most directly, the symptoms of lupus are caused by antibodies that attack components of healthy, normal tissue. For example, when diagnosing lupus, doctors often order an antinuclear antibody (ANA) blood test, which is positive in 97% of lupus patients. However, many people with other autoimmune disorders, or even people without one, also have a positive ANA test. Additional antibody tests are often used to help diagnosis of a patient with a positive ANA test and symptoms of lupus. Another common test looks for anti-dsDNA (double stranded-DNA) antibodies, which compared to ANA, are quite specific to lupus. Others tests include those for antibodies to phospholipids and to Sm proteins in the nucleus. However, the full set of events leading up to lupus is still largely a mystery.
The disease appears to have a hereditary factor, as lupus seems to run in families and be more prevalent in certain ethnic groups. Certain genes have also been linked with lupus, although they are not the sole cause of the disease. This is backed up by the fact that within pairs of identical twins, often (in 75% of cases) only one has the disorder. Not everybody with lupus-associated genes develops it. This information strongly suggests that SLE is caused by a mix of genetic and environmental factors.
Research has found certain genes that seem to correlate with the disease. For example, mutations to the genes of the major histocompatability complex (MHC) have been associated with an increased risk for SLE. The MHC consists of multiple genes, and a number of alleles on various MHC genes have been linked with lupus, particularly within specific populations. The disorder has also been linked to genes that code for Fc gamma receptors, which play a role in clearing antibodies and immune complexes from the bloodstream.
The process of apoptosis, or programmed cell death, is believed to play a significant role in SLE. Cells may perform apoptosis when there is a significant issue, such as a problem with the cell cycle. The deletion of programmed cell death gene 1 (PDCD1), which plays a role in apoptosis, in certain animals has caused symptoms similar to lupus. However, other results concerning this connection have been inconsistent. After the process of apoptosis, the body’s macrophages usually clear out the dead cellular matter. Studies suggest that in lupus patients, this process is defective. When a cell is not cleared away post-apoptosis, the nucleus may break down, releasing auto-antigens (self-antigens). It is quite possible that in turn, the immune system produces a strong reaction to these auto-antigens, causing lupus symptoms.
The environmental factors involved in lupus also have yet to be fully understood. DNA methylation, a process by which genes are deactivated, has been shown to play a role in lupus. A wide variety of environmental factors can cause this process. Some examples of factors that have been linked to lupus include certain medications, sunlight, and infections.
The development of lupus has also been strongly linked to infection by the Epstein-Barr virus (EBV), which causes mononucleosis. This is supported by studies showing that lupus patients have higher concentration of anti-EBV antibodies than the control population, and later research is starting to show a cause-effect relationship. These observations may be caused by a structure that is similar between the EBV antigen and certain auto-antigens. However, as most of the general population has antibodies to EBV, but only a small portion has SLE, more studies are needed about the role of the virus in lupus and its connection with other risk factors.
Approximately 90% of lupus cases occur in women. On a broader scale, women are more likely to develop autoimmune disorders in general. This suggests a role of hormones, particularly estrogen, but no such connection has been proven so far. Studies have shown that females in general have a stronger immune system, and this is likely connected to their higher incidence of autoimmune disorders.
Treatment
In addition to specific treatment for any complications (such as dialysis for kidney failure), most lupus patients are generally treated with immunosuppressant and anti-inflammatory drugs. While this approach is very helpful for lupus symptoms, it leaves patients vulnerable to infections. This compromised immune system has lead to significant illnesses and even death in many patients. In general, however, the benefits are considered to be worth the risk.
Conclusion
Despite the many correlations found in research that help point to the causes of lupus, we do not have a complete understanding of the specific components of this autoimmune disease. Finding out more will aid the development of more specialized drugs, which may have more benefit without the dangers of suppressing a patient’s immune system.
The human immune system is meant to protect us from and attack foreign invaders (known as pathogens), such as influenza viruses or the bacteria that cause tuberculosis. In some cases, however, the immune system attacks normal components of the individual’s own body, such as the myelin sheath of neurons (in the condition multiple sclerosis) or the insulin producing cells of the pancreas (this is the suspected cause of type I diabetes). Systemic Lupus Erythematosus (SLE) is a chronic, potentially life threatening autoimmune condition that can affect any part of the body, causing inflammation. SLE accounts for ~70% of all lupus cases.
There are three other types of lupus: cutaneous, drug-induced, and neonatal. However, these types are relatively uncommon and, generally, less serious. Cutaneous lupus is limited to problems involving the skin, such as rashes. Drug-induced lupus has symptoms similar to SLE, but often goes away months after the offending medication is stopped. Neonatal lupus rarely occurs in newborn children of women with lupus, and the effects usually disappear within a few months.
Lupus, particularly SLE, can have a devastating impact on patients. The disease can interfere with the function of major organs, causing complications such as kidney failure and heart attacks. Daily symptoms, which may include skin problems and joint pain, can have a significant negative impact on functioning and quality of life.
Causes of Lupus
As with many autoimmune disorders, there is still a lot to be discovered about the causes of lupus. Most directly, the symptoms of lupus are caused by antibodies that attack components of healthy, normal tissue. For example, when diagnosing lupus, doctors often order an antinuclear antibody (ANA) blood test, which is positive in 97% of lupus patients. However, many people with other autoimmune disorders, or even people without one, also have a positive ANA test. Additional antibody tests are often used to help diagnosis of a patient with a positive ANA test and symptoms of lupus. Another common test looks for anti-dsDNA (double stranded-DNA) antibodies, which compared to ANA, are quite specific to lupus. Others tests include those for antibodies to phospholipids and to Sm proteins in the nucleus. However, the full set of events leading up to lupus is still largely a mystery.
The disease appears to have a hereditary factor, as lupus seems to run in families and be more prevalent in certain ethnic groups. Certain genes have also been linked with lupus, although they are not the sole cause of the disease. This is backed up by the fact that within pairs of identical twins, often (in 75% of cases) only one has the disorder. Not everybody with lupus-associated genes develops it. This information strongly suggests that SLE is caused by a mix of genetic and environmental factors.
Research has found certain genes that seem to correlate with the disease. For example, mutations to the genes of the major histocompatability complex (MHC) have been associated with an increased risk for SLE. The MHC consists of multiple genes, and a number of alleles on various MHC genes have been linked with lupus, particularly within specific populations. The disorder has also been linked to genes that code for Fc gamma receptors, which play a role in clearing antibodies and immune complexes from the bloodstream.
The process of apoptosis, or programmed cell death, is believed to play a significant role in SLE. Cells may perform apoptosis when there is a significant issue, such as a problem with the cell cycle. The deletion of programmed cell death gene 1 (PDCD1), which plays a role in apoptosis, in certain animals has caused symptoms similar to lupus. However, other results concerning this connection have been inconsistent. After the process of apoptosis, the body’s macrophages usually clear out the dead cellular matter. Studies suggest that in lupus patients, this process is defective. When a cell is not cleared away post-apoptosis, the nucleus may break down, releasing auto-antigens (self-antigens). It is quite possible that in turn, the immune system produces a strong reaction to these auto-antigens, causing lupus symptoms.
The environmental factors involved in lupus also have yet to be fully understood. DNA methylation, a process by which genes are deactivated, has been shown to play a role in lupus. A wide variety of environmental factors can cause this process. Some examples of factors that have been linked to lupus include certain medications, sunlight, and infections.
The development of lupus has also been strongly linked to infection by the Epstein-Barr virus (EBV), which causes mononucleosis. This is supported by studies showing that lupus patients have higher concentration of anti-EBV antibodies than the control population, and later research is starting to show a cause-effect relationship. These observations may be caused by a structure that is similar between the EBV antigen and certain auto-antigens. However, as most of the general population has antibodies to EBV, but only a small portion has SLE, more studies are needed about the role of the virus in lupus and its connection with other risk factors.
Approximately 90% of lupus cases occur in women. On a broader scale, women are more likely to develop autoimmune disorders in general. This suggests a role of hormones, particularly estrogen, but no such connection has been proven so far. Studies have shown that females in general have a stronger immune system, and this is likely connected to their higher incidence of autoimmune disorders.
Treatment
In addition to specific treatment for any complications (such as dialysis for kidney failure), most lupus patients are generally treated with immunosuppressant and anti-inflammatory drugs. While this approach is very helpful for lupus symptoms, it leaves patients vulnerable to infections. This compromised immune system has lead to significant illnesses and even death in many patients. In general, however, the benefits are considered to be worth the risk.
Conclusion
Despite the many correlations found in research that help point to the causes of lupus, we do not have a complete understanding of the specific components of this autoimmune disease. Finding out more will aid the development of more specialized drugs, which may have more benefit without the dangers of suppressing a patient’s immune system.
Glossary
|
Sm proteins – a near universal RNA-binding protein
Major histocompatability complex (MHC) – a set of molecules on the surface of a cell which present an antigen to other cells Fc gamma receptors – proteins which bind to immunoglobulin G (a type of antibody) and immune complexes that contain it, in order to remove them from circulation Immune complex – an antibody connected to an antigen Antigen – a piece of a certain cell presented on the surface by an MHC molecule; this is how the immune system recognizes a certain pathogen |
Methylation – the addition of methyl (CH3) groups to DNA, typically to inactivate a section of it
Epstein-Barr Virus – also known as human herpesvirus 4, a double stranded DNA virus that is extremely common in the human population; in some cases, infection causes mononucleousis Macrophage – a type of leukocyte (white blood cell) that takes in a variety of substances (such as pathogens and cell debris) through phagocytosis |
About the Lupus Foundation of America. (n.d.). Retrieved from http://www.lupus.org/
Anti-dsDNA. (n.d.). Retrieved from http://labtestsonline.org/understanding/analytes/anti-dsdna/tab/test/
Genetics of Systemic Lupus Erythematosus . (n.d.). Retrieved from http://emedicine.medscape.com/article/1884084-overview
Johns Hopkins Lupus Center. (n.d.). Retrieved from http://www.hopkinslupus.org/
Lupus. (n.d.). Retrieved March 3, 2015, from http://www.mayoclinic.org/diseases-conditions/lupus/basics/definition/con-20019676
Perl, A. (n.d.). Pathogenic mechanisms in systemic lupus erythematosus. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20014960
Ramanujam, M., & Davidson, A. (2008). Targeting of the immune system in systemic lupus erythematosus. Expert Reviews in Molecular Medicine, 10. doi:10.1017/S1462399408000562
Ramos, P. S., Brown, E. E., Kimberly, R. P., & Langefeld, C. D. (2010, March 30). Genetic Factors Predisposing to Systemic Lupus Erythematosus and Lupus Nephritis. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847514/
Systemic lupus erythematosus: MedlinePlus Medical Encyclopedia. (n.d.). Retrieved from http://www.nlm.nih.gov/medlineplus/ency/article/000435.htm
Anti-dsDNA. (n.d.). Retrieved from http://labtestsonline.org/understanding/analytes/anti-dsdna/tab/test/
Genetics of Systemic Lupus Erythematosus . (n.d.). Retrieved from http://emedicine.medscape.com/article/1884084-overview
Johns Hopkins Lupus Center. (n.d.). Retrieved from http://www.hopkinslupus.org/
Lupus. (n.d.). Retrieved March 3, 2015, from http://www.mayoclinic.org/diseases-conditions/lupus/basics/definition/con-20019676
Perl, A. (n.d.). Pathogenic mechanisms in systemic lupus erythematosus. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20014960
Ramanujam, M., & Davidson, A. (2008). Targeting of the immune system in systemic lupus erythematosus. Expert Reviews in Molecular Medicine, 10. doi:10.1017/S1462399408000562
Ramos, P. S., Brown, E. E., Kimberly, R. P., & Langefeld, C. D. (2010, March 30). Genetic Factors Predisposing to Systemic Lupus Erythematosus and Lupus Nephritis. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847514/
Systemic lupus erythematosus: MedlinePlus Medical Encyclopedia. (n.d.). Retrieved from http://www.nlm.nih.gov/medlineplus/ency/article/000435.htm
