Rheumatoid Arthritis
Rheumatoid arthritis is a chronic, inflammatory, autoimmune disorder. It primarily affects the joints of the body. Common joints affected by RA are the hands, knees, or ankles. These joints will be affected bilaterally. Joints can be affected elsewhere such as the sternum. However, 40% of patients say they don't experience joint pain. RA can also affect the skin, eyes, lungs, heart, and blood vessels.[3]
The immune system of a person with rheumatoid arthritis will treat the body as a foreigner invader. Recognizing the body as a foreigner invader, the immune system will release inflammatory chemicals that attack the lining of the joints. The inflammation weakens the synovium, the lining of the membranes that surround your joints. The weakening of the synovium causes swelling which leads to bone erosion and joint deformity. The tendons and ligaments that hold the joint together will also weaken as well as stretch which causes the joint to loose its shape and alignment. |
Complications and Causes
There are several complications that can arise from RA: osteoporosis, rheumatoid nodules, dry eyes and mouth, infections, abnormal body composition, carpal tunnel syndrome, heart problems, lung disease, and lymphoma.[4] Currently it is not fully known why people develop RA. But, it is believed the development may have something to do with certain genes being activated by a trigger in the environment or physical or emotional stress. However, there are several genes they think are linked to the cause of RA such as Stat4. There are several risk factors that influence whether or not someone develops RA.
There are several complications that can arise from RA: osteoporosis, rheumatoid nodules, dry eyes and mouth, infections, abnormal body composition, carpal tunnel syndrome, heart problems, lung disease, and lymphoma.[4] Currently it is not fully known why people develop RA. But, it is believed the development may have something to do with certain genes being activated by a trigger in the environment or physical or emotional stress. However, there are several genes they think are linked to the cause of RA such as Stat4. There are several risk factors that influence whether or not someone develops RA.
Stat4 is a possible gene that contributes to the development RA
Stat4 (signal transducer and activator of transcription 4) is activated by the immune system proteins called cytokines. Cytokines are part of the inflammatory response to fight infection. Stat4 is specifically activated by IL2 (interleukin-2) and IL3 (interleukin-3). These interleukin molecules are a subgroup of cytokines.
When Stat4 is activated, it binds to a specific region of DNA and helps regulate transcription of DNA into mRNA. It's role as a regulator of transcription is to be an activator. An activator of transcription binds to an enhancer sequence of the DNA where it will recruit RNA polymerase to come and turn the DNA into mRNA. This is all part of a process with the end goal of creating proteins. These proteins allow certain characteristics, disorders, or disease to present in a person.
The DNA that Stat4 regulates for transcription is involved in T cell maturation that matures into specialized T cells called TH cells as well as natural killer cells [5]. Stat4 regulates two types of T cells, TH1 and TH17. Both of which are the main lymphocytes that trigger autoimmune responses. Th1 produces specific cytokines that will stimulate other immune cells to get rid of foreign invaders in the cell.[5]
Currently the role Stat4 plays in regulating inflammation in women is unknown. However, I hypothesize it to upregulate inflammation in women. This could account for why women are more likely to develop RA than males.
Stat4 (signal transducer and activator of transcription 4) is activated by the immune system proteins called cytokines. Cytokines are part of the inflammatory response to fight infection. Stat4 is specifically activated by IL2 (interleukin-2) and IL3 (interleukin-3). These interleukin molecules are a subgroup of cytokines.
When Stat4 is activated, it binds to a specific region of DNA and helps regulate transcription of DNA into mRNA. It's role as a regulator of transcription is to be an activator. An activator of transcription binds to an enhancer sequence of the DNA where it will recruit RNA polymerase to come and turn the DNA into mRNA. This is all part of a process with the end goal of creating proteins. These proteins allow certain characteristics, disorders, or disease to present in a person.
The DNA that Stat4 regulates for transcription is involved in T cell maturation that matures into specialized T cells called TH cells as well as natural killer cells [5]. Stat4 regulates two types of T cells, TH1 and TH17. Both of which are the main lymphocytes that trigger autoimmune responses. Th1 produces specific cytokines that will stimulate other immune cells to get rid of foreign invaders in the cell.[5]
Currently the role Stat4 plays in regulating inflammation in women is unknown. However, I hypothesize it to upregulate inflammation in women. This could account for why women are more likely to develop RA than males.
Additional Resources
Sources:
1.Frucht, D., Aringer, M., Galon, J., Danning, C., Brown, M., Fan, S., . . . O’Shea, J. (2000, May 01). Stat4 is expressed in Activated peripheral BLOOD MONOCYTES, DENDRITIC cells, and Macrophages at sites of Th1-Mediated Inflammation. Retrieved February 2, 2021, from https://www.jimmunol.org/content/164/9/4659.long
2.JAK-STAT signaling pathway. (2021, January 11). Retrieved February 4, 2021, from https://en.wikipedia.org/wiki/JAK-STAT_signaling_pathway
3.Rheumatoid arthritis. (2019, March 01). Retrieved February 1, 2021, from https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648
4.Rheumatoid arthritis. (n.d.). Retrieved February 3, 2021, from https://www.arthritis.org/diseases/rheumatoid-arthritis
5.STAT4 gene: MedlinePlus Genetics. (2020, August 18). Retrieved February 1, 2021, from https://medlineplus.gov/genetics/gene/stat4/
6.STAT4 signal transducer and activator of Transcription 4 [Homo Sapiens (human)] - gene - NCBI. (n.d.). Retrieved February 22, 2021, from https://www.ncbi.nlm.nih.gov/gene/6775/
Images:
https://cdn.shortpixel.ai/client/q_lossy,ret_img,w_2400/https://www.drlox.com/wp-content/uploads/2019/11/stages-of-rheumatoid-arthritis.jpg
https://biorender.com/
https://tse4.mm.bing.net/th?id=OIP.PMLUOi64Mfyu8dNd1tevlQHaHX&pid=Api
https://tse3.mm.bing.net/th?id=OIP.pMNFpTuj-PtM1JnJ5VfRAQHaE8&pid=Api
https://tse1.mm.bing.net/th?id=OIP.xxpWGGq9xvw2wnEb58-yDwHaFQ&pid=Api
1.Frucht, D., Aringer, M., Galon, J., Danning, C., Brown, M., Fan, S., . . . O’Shea, J. (2000, May 01). Stat4 is expressed in Activated peripheral BLOOD MONOCYTES, DENDRITIC cells, and Macrophages at sites of Th1-Mediated Inflammation. Retrieved February 2, 2021, from https://www.jimmunol.org/content/164/9/4659.long
2.JAK-STAT signaling pathway. (2021, January 11). Retrieved February 4, 2021, from https://en.wikipedia.org/wiki/JAK-STAT_signaling_pathway
3.Rheumatoid arthritis. (2019, March 01). Retrieved February 1, 2021, from https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648
4.Rheumatoid arthritis. (n.d.). Retrieved February 3, 2021, from https://www.arthritis.org/diseases/rheumatoid-arthritis
5.STAT4 gene: MedlinePlus Genetics. (2020, August 18). Retrieved February 1, 2021, from https://medlineplus.gov/genetics/gene/stat4/
6.STAT4 signal transducer and activator of Transcription 4 [Homo Sapiens (human)] - gene - NCBI. (n.d.). Retrieved February 22, 2021, from https://www.ncbi.nlm.nih.gov/gene/6775/
Images:
https://cdn.shortpixel.ai/client/q_lossy,ret_img,w_2400/https://www.drlox.com/wp-content/uploads/2019/11/stages-of-rheumatoid-arthritis.jpg
https://biorender.com/
https://tse4.mm.bing.net/th?id=OIP.PMLUOi64Mfyu8dNd1tevlQHaHX&pid=Api
https://tse3.mm.bing.net/th?id=OIP.pMNFpTuj-PtM1JnJ5VfRAQHaE8&pid=Api
https://tse1.mm.bing.net/th?id=OIP.xxpWGGq9xvw2wnEb58-yDwHaFQ&pid=Api
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