Systemic Lupus Erythematosus Research Paper
Natalie Rauschenbach
Lupus Nephritis
Abstract
Systemic lupus erythematosus is the most common form of lupus ranges from mild to severe. Lupus is an autoimmune disease which means the person’s immune system cannot tell the difference of healthy tissue and infected tissue. This issue confuses the body and instead of creating antibodies to destroy the damaged/infected tissue and the body destroys the person’s healthy tissue. The study of focus determines whether current treatments for lupus are still valid including “corticosteroids, other immunosuppressive drugs, such as azathioprine and cyclophosphamide, and adjunctive therapies, including dialysis and renal transplantation” (Leandro et al.). The other goal of this study was to find …show more content…
whether the effects of B-cell depletion with rituximab for patients that received the previous treatments of immunosuppressants but they failed resulting in the returning of symptoms involved with systemic lupus.
Introduction
Lupus nephritis is a kidney disorder that is a complication of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease which means there is a problem with the body 's immune system. Normally, the immune system helps protect the body from harmful substances. But in patients with an autoimmune disease, the immune system cannot tell the difference between harmful substances and healthy ones. As a result, the immune system attacks otherwise healthy cells and tissue. SLE may damage different parts of the kidney, leading to interstitial nephritisinterstitial nephritis, and nephrotic syndromenephrotic syndromemembranous GN. SLE has a different name when it involves the inflammation of the kidneys, Lupus Nephritis. Since lupus nephritis involves is the inflammation of the kidneys, it affects the kidney’s ability to filter the waste from the blood and can be so damaging that a kidney transplant would be needed. Also, the inflammation of the kidneys can cause “an increase in blood pressure, inflammation of the nervous system and the brain, which can cause memory problems, confusion, headaches and strokes”(Lupus foundation). If these damages continue, it may rapidly worsen to kidney failure. Lupus nephritis affects approximately 3 out of every 10,000 people (Lupus foundation). In children with SLE, about half will have some form or degree of kidney involvement (Lupus Foundation). More than half of patients have not had other symptoms of SLE when they …show more content…
are diagnosed with lupus nephritis (Lupus Foundation). SLE is most common in women ages 20 – 40 (Lupus foundation).
Like previously mentioned, lupus nephritis is the inflammation of the kidney(s) and it branches off of systemic lupus. Individuals with lupus nephritis will experience possible weight gain, high blood pressure, dark urine, or swelling around the eyes, legs, ankles, or fingers. However, some people with lupus may not experience any of these symptoms and urine tests must be conducted in order to confirm the individual has lupus. Urine samples will show whether there will be a foamy appearance to the urine and/or whether there is blood and protein in it. Blood and protein in the urine is an apparent sign of kidney damage and the issue must be taken care of as soon as possible in order to prevent further damage. Furthermore, there are two other tests that can confirm if an individual has lupus. One is a blood test. The kidneys remove waste materials like creatinine and urea from the blood. If the blood contains high levels of these substances, kidney function is declining. Second, a kidney biopsy can be conducted. A biopsy is a procedure to obtain a tissue sample for examination with a microscope. To obtain a sample of your kidney tissue, a doctor will insert a long needle through the skin. Examining the tissue with a microscope can confirm the diagnosis of lupus nephritis and help to determine how far the disease has progressed. Treatment of lupus nephritis depends on the symptoms and test results. Medicines called corticosteroids can decrease swelling and inflammation by suppressing the immune system. Additional immunosuppressive drugs related to cancer and drugs used to prevent rejection of organ transplants may also be used. In severe cases, a doctor may prescribe cyclophosphamide (Cytoxan, Neosar) or mycophenolate (CellCept). Newer experimental treatments include a drug called rituximab (Rituxan) (Leandro et al.).
Methods For the journal article that we choose to research and learn about was about b-cell depletion via rituximab treatments. All of the patients that were being used in this testing had to meet several criteria; they were treated on urgent basis, other immunosuppressive treatments were not working, and local hospitals approved of the testing on the patients. The groups were tested in several different ways “The first six patients (patients 1–6) were treated with two infusions of 500 mg rituximab (half dose) and two infusions of 750 mg cyclophosphamide under oral steroid cover (2 x prednisolone 60 mg for 5 days) given 2 weeks apart. Subsequently the patients were treated with a similar protocol but with full-dose rituximab (2 x 1000 mg) and intravenous methylprednisolone (2 x 250 mg) instead of oral steroids. Two patients received rituximab monotherapy: one had an allergy to cyclophosphamide (patient 12) and the other patient refused to have the drug (patient 9). Patients were allowed to continue prednisolone and hydroxychloroquine. Other immunosuppressives were stopped at baseline except for two patients who continued their azathioprine (patient 15 started at baseline on 100 mg; patient 16 continued on 150 mg)” (M. J. Leandro et al.). The clinic kept check ups on the patients every month to two months in there lupus clinics, they took many blood test during these periods to test if the initial medication as well as the other patients medications. They were rated on a scale of A to E, A being the most active and E being the least active. “The patients’ routine full blood count, serum creatinine, C3 (laser nephelometry), total immunoglobulin and dsDNA binding (Shield Diagnostics, Dundee, UK; normal <50 units/ml) and urine protein to creatinine ratio were tested in the hospital routine laboratories”(Leandro et al.).
Results The methods previously mentioned showed that the patients obviously did not react to the current methods of treatment for lupus. The immunosuppressants and the corticosteroids did not provide the desired reaction of reducing inflammation in the kidneys; therefore, they were introduced to this innovative treatment. In the end, the patients did see a significant decrease in inflammation which means that B-lymphocyte depletion is a valid treatment for reducing inflammation in lupus patients.
Discussion
There are numerous drugs and immunosuppressants one can take in order to improve the symptoms of lupus.
However, two studies have shown that by depleting a certain cell directly linked to lupus, one can drastically improve their condition. In the first study conducted by Leanardo, Cambridge, Edwards, Ehrenstein, and Isenberg (2005), they depleted B-cells in patients with systemic lupus erythematosus. These researchers depleted the B lypmphocytes in individuals by using rituxumab, an antibody that is effective in depleting normal and malignant B lymphocytes. Researchers initially began using rituxumab for rheumatoid arthritis which mainly inflames the joints in mainly elderly individuals. Since lupus involves the inflammation of the kidneys, researchers sought to discover whether rituxumab would reduce inflammation involved with lupus. In the first study, twenty-four patients were treated with an average age being 28.9 years and the mean disease duration was 7.8 years (Leandro et al). The patients were divided into groups and each group received a different dosage of rituxumab. In the end, the B-cell depletion in all the groups occurred and the researchers claim that B-cell depletion may be a very useful addition to the range of therapies available for patients with very active lupus (Leandro et al).
The second study was conducted by Chan, Madaio, and Shlomchik (1999) using the same methods of curing lupus; however, the study used animals instead of humans. Although they used
animals, the results were concurrent with those in the previous study using humans. The results indicate that B cells/lymphocytes are essential in promoting systemic autoimmunity (Chan et al.). The results provide further rationale for B cell suppression as therapy for systemic lupus erythematosus.
Future Discussions
Overall, Lupus is a disease associated with the inflammation of the kidneys and it occurs due to the malfunction of the immune system. Furthermore, patients may suffer from other symptoms of lupus unrelated to kidney function. Such symptoms can include arthritis, fevers, gastro-intestinal disturbances, headaches, fatigue, and fluid in the joints. Normally steroids and immunosuppressants are given to the inflicted individuals; however, these studies show that by targeting B-cells one can see drastic improvement. In the future, this treatment should become more common because of its specific properties. The patients in the first study were used because the mainstream treatments did not work. All the patients that followed protocol saw improvement which means that, by depleting B-cells, lupus may have a more concrete cure.
Works Cited
Chan, Owen T.M., Michael P. Madalo, and Mark J. Shlomchik. "B Cells Are Required for Lupus Nephritis in the Polygenic, Fas-Intact MRL Model of Systemic Autoimmunity." The Journal of Immunology 163 (1999): 3592-596. Web. 29 July 2010.
Leandro, M. J., G. Cambridge, J. C. Edwards, M. R. Ehrenstein, and D. A. Isenberg. "B-cell Depletion in the Treatment of Patients with Systemic Lupus Erythematosus:a Longitudinal Analysis of 24 Patients." Rheumatology 44 (2005): 1542-545. 27 Sept. 2005. Web. 29 July 2010.
Lupus Foundation of America. Web. 29 July 2010. <http://www.lupus.org/>.
Lupus Nephritis
Abstract
Systemic lupus erythematosus is the most common form of lupus ranges from mild to severe. Lupus is an autoimmune disease which means the person’s immune system cannot tell the difference of healthy tissue and infected tissue. This issue confuses the body and instead of creating antibodies to destroy the damaged/infected tissue and the body destroys the person’s healthy tissue. The study of focus determines whether current treatments for lupus are still valid including “corticosteroids, other immunosuppressive drugs, such as azathioprine and cyclophosphamide, and adjunctive therapies, including dialysis and renal transplantation” (Leandro et al.). The other goal of this study was to find …show more content…
whether the effects of B-cell depletion with rituximab for patients that received the previous treatments of immunosuppressants but they failed resulting in the returning of symptoms involved with systemic lupus.
Introduction
Lupus nephritis is a kidney disorder that is a complication of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease which means there is a problem with the body 's immune system. Normally, the immune system helps protect the body from harmful substances. But in patients with an autoimmune disease, the immune system cannot tell the difference between harmful substances and healthy ones. As a result, the immune system attacks otherwise healthy cells and tissue. SLE may damage different parts of the kidney, leading to interstitial nephritisinterstitial nephritis, and nephrotic syndromenephrotic syndromemembranous GN. SLE has a different name when it involves the inflammation of the kidneys, Lupus Nephritis. Since lupus nephritis involves is the inflammation of the kidneys, it affects the kidney’s ability to filter the waste from the blood and can be so damaging that a kidney transplant would be needed. Also, the inflammation of the kidneys can cause “an increase in blood pressure, inflammation of the nervous system and the brain, which can cause memory problems, confusion, headaches and strokes”(Lupus foundation). If these damages continue, it may rapidly worsen to kidney failure. Lupus nephritis affects approximately 3 out of every 10,000 people (Lupus foundation). In children with SLE, about half will have some form or degree of kidney involvement (Lupus Foundation). More than half of patients have not had other symptoms of SLE when they …show more content…
are diagnosed with lupus nephritis (Lupus Foundation). SLE is most common in women ages 20 – 40 (Lupus foundation).
Like previously mentioned, lupus nephritis is the inflammation of the kidney(s) and it branches off of systemic lupus. Individuals with lupus nephritis will experience possible weight gain, high blood pressure, dark urine, or swelling around the eyes, legs, ankles, or fingers. However, some people with lupus may not experience any of these symptoms and urine tests must be conducted in order to confirm the individual has lupus. Urine samples will show whether there will be a foamy appearance to the urine and/or whether there is blood and protein in it. Blood and protein in the urine is an apparent sign of kidney damage and the issue must be taken care of as soon as possible in order to prevent further damage. Furthermore, there are two other tests that can confirm if an individual has lupus. One is a blood test. The kidneys remove waste materials like creatinine and urea from the blood. If the blood contains high levels of these substances, kidney function is declining. Second, a kidney biopsy can be conducted. A biopsy is a procedure to obtain a tissue sample for examination with a microscope. To obtain a sample of your kidney tissue, a doctor will insert a long needle through the skin. Examining the tissue with a microscope can confirm the diagnosis of lupus nephritis and help to determine how far the disease has progressed. Treatment of lupus nephritis depends on the symptoms and test results. Medicines called corticosteroids can decrease swelling and inflammation by suppressing the immune system. Additional immunosuppressive drugs related to cancer and drugs used to prevent rejection of organ transplants may also be used. In severe cases, a doctor may prescribe cyclophosphamide (Cytoxan, Neosar) or mycophenolate (CellCept). Newer experimental treatments include a drug called rituximab (Rituxan) (Leandro et al.).
Methods For the journal article that we choose to research and learn about was about b-cell depletion via rituximab treatments. All of the patients that were being used in this testing had to meet several criteria; they were treated on urgent basis, other immunosuppressive treatments were not working, and local hospitals approved of the testing on the patients. The groups were tested in several different ways “The first six patients (patients 1–6) were treated with two infusions of 500 mg rituximab (half dose) and two infusions of 750 mg cyclophosphamide under oral steroid cover (2 x prednisolone 60 mg for 5 days) given 2 weeks apart. Subsequently the patients were treated with a similar protocol but with full-dose rituximab (2 x 1000 mg) and intravenous methylprednisolone (2 x 250 mg) instead of oral steroids. Two patients received rituximab monotherapy: one had an allergy to cyclophosphamide (patient 12) and the other patient refused to have the drug (patient 9). Patients were allowed to continue prednisolone and hydroxychloroquine. Other immunosuppressives were stopped at baseline except for two patients who continued their azathioprine (patient 15 started at baseline on 100 mg; patient 16 continued on 150 mg)” (M. J. Leandro et al.). The clinic kept check ups on the patients every month to two months in there lupus clinics, they took many blood test during these periods to test if the initial medication as well as the other patients medications. They were rated on a scale of A to E, A being the most active and E being the least active. “The patients’ routine full blood count, serum creatinine, C3 (laser nephelometry), total immunoglobulin and dsDNA binding (Shield Diagnostics, Dundee, UK; normal <50 units/ml) and urine protein to creatinine ratio were tested in the hospital routine laboratories”(Leandro et al.).
Results The methods previously mentioned showed that the patients obviously did not react to the current methods of treatment for lupus. The immunosuppressants and the corticosteroids did not provide the desired reaction of reducing inflammation in the kidneys; therefore, they were introduced to this innovative treatment. In the end, the patients did see a significant decrease in inflammation which means that B-lymphocyte depletion is a valid treatment for reducing inflammation in lupus patients.
Discussion
There are numerous drugs and immunosuppressants one can take in order to improve the symptoms of lupus.
However, two studies have shown that by depleting a certain cell directly linked to lupus, one can drastically improve their condition. In the first study conducted by Leanardo, Cambridge, Edwards, Ehrenstein, and Isenberg (2005), they depleted B-cells in patients with systemic lupus erythematosus. These researchers depleted the B lypmphocytes in individuals by using rituxumab, an antibody that is effective in depleting normal and malignant B lymphocytes. Researchers initially began using rituxumab for rheumatoid arthritis which mainly inflames the joints in mainly elderly individuals. Since lupus involves the inflammation of the kidneys, researchers sought to discover whether rituxumab would reduce inflammation involved with lupus. In the first study, twenty-four patients were treated with an average age being 28.9 years and the mean disease duration was 7.8 years (Leandro et al). The patients were divided into groups and each group received a different dosage of rituxumab. In the end, the B-cell depletion in all the groups occurred and the researchers claim that B-cell depletion may be a very useful addition to the range of therapies available for patients with very active lupus (Leandro et al).
The second study was conducted by Chan, Madaio, and Shlomchik (1999) using the same methods of curing lupus; however, the study used animals instead of humans. Although they used
animals, the results were concurrent with those in the previous study using humans. The results indicate that B cells/lymphocytes are essential in promoting systemic autoimmunity (Chan et al.). The results provide further rationale for B cell suppression as therapy for systemic lupus erythematosus.
Future Discussions
Overall, Lupus is a disease associated with the inflammation of the kidneys and it occurs due to the malfunction of the immune system. Furthermore, patients may suffer from other symptoms of lupus unrelated to kidney function. Such symptoms can include arthritis, fevers, gastro-intestinal disturbances, headaches, fatigue, and fluid in the joints. Normally steroids and immunosuppressants are given to the inflicted individuals; however, these studies show that by targeting B-cells one can see drastic improvement. In the future, this treatment should become more common because of its specific properties. The patients in the first study were used because the mainstream treatments did not work. All the patients that followed protocol saw improvement which means that, by depleting B-cells, lupus may have a more concrete cure.
Works Cited
Chan, Owen T.M., Michael P. Madalo, and Mark J. Shlomchik. "B Cells Are Required for Lupus Nephritis in the Polygenic, Fas-Intact MRL Model of Systemic Autoimmunity." The Journal of Immunology 163 (1999): 3592-596. Web. 29 July 2010.
Leandro, M. J., G. Cambridge, J. C. Edwards, M. R. Ehrenstein, and D. A. Isenberg. "B-cell Depletion in the Treatment of Patients with Systemic Lupus Erythematosus:a Longitudinal Analysis of 24 Patients." Rheumatology 44 (2005): 1542-545. 27 Sept. 2005. Web. 29 July 2010.
Lupus Foundation of America. Web. 29 July 2010. <http://www.lupus.org/>.