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| ====== Lupus ====== | ====== Lupus ====== | ||
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| ====== Epidemiology ====== | ====== Epidemiology ====== | ||
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| Women are more likely to be affected (9 times more likely than men). After puberty and before menopause women have the highest rate of getting the disease (15:1 compared to men) (Askanase et al., 2012). Non-Caucasians are more likely to have the disease than Caucasians (Lau et al., 2006). In a paper by Lau et al (2006), they looked at prevalence records of lupus around the world and compared them to different ethnic groups. They found that Indians, Afro-Americans, Chinese and Japanese had higher rates of prevalence than Caucasians from North America or England. There were also reported differences in the instances of the disease between the different ethnicities. They also noted that these groups may have less socio economic advantages for dealing with the disease making their rates inflated compared to Caucasians. | Women are more likely to be affected (9 times more likely than men). After puberty and before menopause women have the highest rate of getting the disease (15:1 compared to men) (Askanase et al., 2012). Non-Caucasians are more likely to have the disease than Caucasians (Lau et al., 2006). In a paper by Lau et al (2006), they looked at prevalence records of lupus around the world and compared them to different ethnic groups. They found that Indians, Afro-Americans, Chinese and Japanese had higher rates of prevalence than Caucasians from North America or England. There were also reported differences in the instances of the disease between the different ethnicities. They also noted that these groups may have less socio economic advantages for dealing with the disease making their rates inflated compared to Caucasians. | ||
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| - | ====== Transmission ====== | ||
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| - | The natural vertebrate host of Zika virus in vertebrates were primarily monkeys. The infection normally spreads in a mosquito-monkey-mosquito cycle with the occasional infection of humans. Prior to the current pandemic that began in 2007, Zika spill over to humans rarely occurred. The primary mode of ZIKV transmission in humans is through the bite of an infected Aedes aegypti mosquito as summarised in Figure 2, other modes of transmission includes transmission through sexual contact, blood transfusions, laboratory exposures and maternal to fetal transmission through pregnancy. The transmission of ZIKV infection is so effective that by the end of 2016 more than 50 countries have reported cases of active cases of transmission though one or more means (CDC, 2018). | ||
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| - | <box 72% round | >{{ :zika-transmission.png?650 |}}</box| Figure 2: A summary of the most reported forms of Zika Virus transmission (CDC, 2018) > | ||
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| - | Although the primary mode of transmission is thought to be through the bite of the female Aedes aegypti mosquito, ZIKV has been isolated in about 6 other mosquitoes in the Aedes genus and 5 other species of mosquitoes. The truth is that the true extent of Zika vectors remains unknown (Ayres 2016)(Hayes, 2009). These posses a significant problem as one of the species of mosquitoes capable of carrying ZIKV has rapidly expanded across all continents. There have been confirmed cases of sexual transmission by both males and females in 6 countries including the USA, but there have been no confirmed cases of transmission through blood transfusions in USA although there are suspected cases in Brazil. ZIKV can also be transmitted through laboratory exposure and through mother to child during all stages of pregnancy. To date there have been only three reported case of ZIKV transmission through laboratory exposure, one in the USA and two in Italy. The recent discovery of ZIKV RNA in most bodily fluids suggest the presence of other modes of transmission (CDC 2018). | ||
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| ====== Pathogenesis ====== | ====== Pathogenesis ====== | ||
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| In patients with Lupus the main cells affected within the innate immunity are Dendritic Cells (DC) and Neutrophils (Rahman & Isenberg, 2008). DCs serve to process antigens (foreign particles) and present them to T-cells. In Lupus patients DCs have been linked to an increase in the humoral response and expansion of autoreactive T-cells and B-cells (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Neutrophils are granulocytes which aid in killing microbes by NETs (Neutrophil Extracellular Trap). This is a process in which DNA is released into the extracellular fluid and forms web structures that attach to pathogens preventing their mobility and spread. In Lupus these NETs undergo NETosis (apoptosis of the NETs) which results in a large accumulation of DNA which serves as autoantigens for DCs (Fortuna & Brennan, 2013). | In patients with Lupus the main cells affected within the innate immunity are Dendritic Cells (DC) and Neutrophils (Rahman & Isenberg, 2008). DCs serve to process antigens (foreign particles) and present them to T-cells. In Lupus patients DCs have been linked to an increase in the humoral response and expansion of autoreactive T-cells and B-cells (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Neutrophils are granulocytes which aid in killing microbes by NETs (Neutrophil Extracellular Trap). This is a process in which DNA is released into the extracellular fluid and forms web structures that attach to pathogens preventing their mobility and spread. In Lupus these NETs undergo NETosis (apoptosis of the NETs) which results in a large accumulation of DNA which serves as autoantigens for DCs (Fortuna & Brennan, 2013). | ||
| - | {{:t_cell.jpeg?direct&300 | Interaction between T-cell and APC}}{{ :b_cell.jpeg?direct&300| B-cell complex with T-cell}} | + | {{:t_cell.jpeg?direct&300 |}}{{ :b_cell.jpeg?direct&300|}} |
| T-cell receptors (TCR) are located on the surface of T-cells. These receptors interact with the antigen that is presented by the APC (antigen presenting cell) or DC. The APC and T-cell form a complex with the TCR, and MHC and antigen (Rahman & Isenberg, 2008). However binding of the antigen-MHC complex does not result in a reaction. Instead binding of costimulatory ligands facilitate stimulation or inhibition. Stimulation results in recruitment of B-cells which form a new complex with the T-cell and antigen (Rahman & Isenberg, 2008). The cells stimulate the other in that binding of the B-cell CD40 to the CD40 ligand on the T-cell results in a release of cytokines from the T-cell. The cytokines stimulate B cell division, shift the antibody production from IgM to IgG, and allow for molecular changes in the antibody produced to increase affinity for the antigen (Rahman & Isenberg, 2008). The effect of the T-cell on the B-cell is based on its affinity to the antigen. Higher affinity of the T-cell to the antigen results in a greater response by the B cell. | T-cell receptors (TCR) are located on the surface of T-cells. These receptors interact with the antigen that is presented by the APC (antigen presenting cell) or DC. The APC and T-cell form a complex with the TCR, and MHC and antigen (Rahman & Isenberg, 2008). However binding of the antigen-MHC complex does not result in a reaction. Instead binding of costimulatory ligands facilitate stimulation or inhibition. Stimulation results in recruitment of B-cells which form a new complex with the T-cell and antigen (Rahman & Isenberg, 2008). The cells stimulate the other in that binding of the B-cell CD40 to the CD40 ligand on the T-cell results in a release of cytokines from the T-cell. The cytokines stimulate B cell division, shift the antibody production from IgM to IgG, and allow for molecular changes in the antibody produced to increase affinity for the antigen (Rahman & Isenberg, 2008). The effect of the T-cell on the B-cell is based on its affinity to the antigen. Higher affinity of the T-cell to the antigen results in a greater response by the B cell. | ||
| The antibodies that are produced by the B cell are known as autoantibodies because they bind to molecules that the body has in abundance such as DNA. The main antigen in Lupus patients is double stranded DNA (Rahman & Isenberg, 2008; Elkon & Casali, 2008; Fortuna & Brennan, 2013). Once the anti-DNA antibody binds to the antigen they form a antigen-antibody complex inducing inflammation at the tissue (Elkon & Casali, 2008; Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). It has been proposed that this complex migrates to the renal glomerular basement membrane and activates complement and promotes inflammation in kidneys which is characteristic of Lupus (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Another theory suggests antibodies cross react with proteins in kidney thereby having an effect. Studies demonstrated that anti-DNA antibodies cross reacted with alpha actin which is a protein critical to maintaining function of renal podocytes (cells of the filtration barrier) (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). | The antibodies that are produced by the B cell are known as autoantibodies because they bind to molecules that the body has in abundance such as DNA. The main antigen in Lupus patients is double stranded DNA (Rahman & Isenberg, 2008; Elkon & Casali, 2008; Fortuna & Brennan, 2013). Once the anti-DNA antibody binds to the antigen they form a antigen-antibody complex inducing inflammation at the tissue (Elkon & Casali, 2008; Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). It has been proposed that this complex migrates to the renal glomerular basement membrane and activates complement and promotes inflammation in kidneys which is characteristic of Lupus (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Another theory suggests antibodies cross react with proteins in kidney thereby having an effect. Studies demonstrated that anti-DNA antibodies cross reacted with alpha actin which is a protein critical to maintaining function of renal podocytes (cells of the filtration barrier) (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). | ||
| - | {{ :total_lupus.jpeg?direct&300 |}} | + | <box 50%| > {{ :total_lupus.jpeg?direct&300 |}} </box| Overview of immune response in Lupus (https://www-nejm-org.libaccess.lib.mcmaster.ca/doi/full/10.1056/NEJMra071297) > |
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| The fifth category for drugs involves Anticoagulants and Monoclonal Antibodies. Anticoagulants are a type of drug that assist in blood-thinning, which inherently reduces blood clots. Monoclonal antibodies are a new genre of drugs that are given via IV and target immune cells. They help reduce the need for steroid treatment, but these drugs have not been thoroughly tested in huge clinical populations. | The fifth category for drugs involves Anticoagulants and Monoclonal Antibodies. Anticoagulants are a type of drug that assist in blood-thinning, which inherently reduces blood clots. Monoclonal antibodies are a new genre of drugs that are given via IV and target immune cells. They help reduce the need for steroid treatment, but these drugs have not been thoroughly tested in huge clinical populations. | ||
| - | For individuals that wish to stay away from pharmaceutical approaches, a few lifestyle changes can increase the quality of life for patients with lupus. By eating a balanced diet, getting plenty of sleep and excesiring, you can seriously offset some of the chronic symptoms lupus causes. | + | For individuals that wish to stay away from pharmaceutical approaches, a few lifestyle changes can increase the quality of life for patients with lupus. By eating a balanced diet, getting plenty of sleep and exercise, you can seriously offset some of the chronic symptoms lupus causes. |
| + | ======Conclusion====== | ||
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| + | In conclusion, Lupus is a chronic autoimmune disorder that causes diverse abnormalities in various areas and systems of the body. Considering that the signs and symptoms of this disorder vary from person to person, and are on and off, it is difficult to determine a diagnosis. Thus, there needs to be advancements in research for discovering methods for early Lupus diagnosis to meet its unique mechanism characteristics. Additionally, another area for future Lupus-related research is advancements in finding a cure for Lupus considering that there are only treatments for management currently available. | ||
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| ======References====== | ======References====== | ||
| + | Askanase, A., Shum, K., & Mitnick, H. (2012). Systemic lupus erythematosus: an overview. Social work in health care, 51(7), 576-586. | ||
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| + | Adelman, D. C., Saltiel, E., & Klinenberg, J. R. (1986, February). The neuropsychiatric manifestations of systemic lupus erythematosus: an overview. In Seminars in arthritis and rheumatism (Vol. 15, No. 3, pp. 185-199). WB Saunders. | ||
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| + | Brazier, Y. (2018, November 12). What is lupus? Medical News Today. Retrieved from https://www.medicalnewstoday.com/articles/323653.php | ||
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| + | Elkon, K., & Casali, P. (2008). Nature and functions of autoantibodies. Nature clinical practice. Rheumatology, 4(9), 491-8. | ||
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| + | Fortuna, G., & Brennan, M. (2013). Systemic lupus erythematosus. Dental Clinics of North America, 57(4), 631-655. http://dx.doi.org/10.1016/j.cden.2013.06.003 | ||
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| + | John Hopkins Lupus Center. (2018). Lupus tests. Retrieved from https://www.hopkinslupus.org/lupus-tests/ | ||
| + | Lau, C. S., Yin, G., & Mok, M. Y. (2006). Ethnic and geographical differences in systemic lupus erythematosus: an overview. Lupus, 15(11), 715-719. | ||
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| + | Lupus Foundation of America. (2013). How lupus is diagnosed: an overview. Retrieved from https://www.lupus.org/resources/how-lupus-is-diagnosed-an-overview | ||
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| + | Mielczarek, L. (2017). Living-Symptoms of SLE. Retrieved from https://www.lupuscanada.org/living-symptoms-of-sle | ||
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| + | Rahman, A., & Isenberg, D. A. (2008). Systemic Lupus Erythematosus. New England Journal of Medicine, 358(9), 929–939. https://doi.org/10.1056/NEJMra071297 | ||
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| + | Suryanarayan, D. & Garcia, D. (2014). Anti-phospholipid antibodies and pregnancy. The Hematologist, 11(4). | ||
| + | Walling, H. W., & Sontheimer, R. D. (2009). Cutaneous lupus erythematosus. American journal of clinical dermatology, 10(6), 365-381. | ||
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