Rheumatoid Arthritis-Links Between the Immune System and the Lymphatic System

Attached is my written statement for my STEAM Project:

I chose to do my research and project on the objective of the role of the lymphatic system in the immune response. To go beyond what we learned in class, I researched the autoimmune disorder, Rheumatoid Arthritis (RA), and how it is related to a dysfunctional immune system and the relationship to the lymphatic system. I chose to draw an infographic comparing a normal joint and a joint with RA and additionally including information about the lymphatic and immune functions for each. According to the Arthritis Foundation, “Rheumatoid Arthritis (RA) causes joint inflammation and pain. It happens when the immune system doesn’t work properly and attacks the lining of the joints, called the synovium”. Joints swell in rheumatoid arthritis because of improper drainage of lymphatic fluid.

The lymphatic system and immune system work closely together to protect the body from pathogens. The lymphatic system is the system of vessels, cells, and organs that carries excess fluids to the bloodstream and filters pathogens from the blood. The lymphatic system drains fluids from the body and returns them back to the bloodstream. It drains the excess fluid and empties it back into the bloodstream via a series of vessels, trunks, and ducts. The lymphatic system also has small bean-shaped organs throughout the body called the lymph nodes. The immune system uses lymph nodes as major areas of development for immune response. Immune system cells also use lymphatic vessels to make their way from interstitial fluid back into the circulation.

Rheumatoid arthritis is an autoimmune disorder where immune cells cause inflammation in the synovium. This inflammation becomes chronic, and the synovium thickens due to an increase of cells, production of proteins, and other factors in the joint, which can lead to pain, redness, and warmth. As RA progresses, the thickened and inflamed synovium pushes further into the joint and destroys the cartilage and bone within the joint (Overview of Rheumatoid Arthritis, 2023). Though there is no cure for RA, there are a variety of treatments. One of which is targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis. A study published in 2018 done by researchers from University of Rochester School of Medicine and Johns Hopkins University observed in their research, “that lymphatic drainage increases at the onset of inflammatory-erosive arthritis but, as inflammation progresses to a more chronic phase, lymphatic clearance declines and both structural and cellular changes are observed in the draining lymph node. Specifically, chronic damage to the lymphatic vessel from persistent inflammation results in loss of lymphatic vessel contraction followed by lymph node collapse, reduced lymphatic drainage, and ultimately severe synovitis and joint erosion” (Bouta et al., 2018). As the immune system fails with this autoimmune system, the lymphatic system’s functionality also declines. The study concluded that lymphatic treatment during the “collapsed phase” of lymphatic function may be a viable treatment option for preventing joint inflammation with inflammatory arthritis. This conclusion was made based on “Murine models [that] demonstrated that dramatic changes in lymphatic vessel function occur during the pathogenesis of inflammatory arthritis; these changes include an initial compensatory expanding phase in which the lymph node expands in size and lymphatic contraction and clearance are proficient, followed by a collapsed phase in which lymph nodes decrease in volume and there is a loss of the intrinsic lymphatic contraction. This dichotomy is mirrored by joint inflammation, where knee inflammation is not apparent until the collapsed phase, suggesting that targeting lymphatic function could be a potential treatment option and a promising area for future research”. In my infographic, I summarized the two stages of alterations to lymphatic function in RA. A more detailed explanation of the autoimmune disorder’s effect on the lymphatic system is “that together with the joint inflammation occurring in RA, the local lymphatics undergo two stages of alterations. As a response to the initial, pre-arthritic, synovial inflammation, the lymphatics undergo an “expansion phase,” whereby they increase their capacity to remove excess cellular debris and inflammatory cells from the site of inflammation; whether by lymphangiogenesis, or by increased lymphatic vessel contraction frequency. This process is important to allow for the resolution of the inflammatory process; if the expansion process is stunted, by inhibition of lymphangiogenesis for example, the joint inflammation becomes more severe and clinical synovitis develops. Beyond the lymphatic vessel changes, the draining lymph nodes themselves increase in size during the expansion phase, likely due to increased volume and pressure of fluid within the afferent vessels , intra-nodal lymphangiogenesis and infiltration of a unique subtype of IgM+CD23+CD21hiCD1dhi B cells found in inflamed lymph nodes, known as Bin cells” (Schwartz et al., 2019).

The immune system and the lymphatic system are deeply intertwined with each other to protect the body from pathogens. In the case of RA, this relationship is highlighted by the dysfunction of the immune system resulting in a decline of function in the lymphatic system. The relationship between the two systems is also revealed by a potential treatment for RA being to target the lymphatic system to treat the autoimmune disorder.

Word Count: 869

References

Bouta, E. M., Bell, R. D., Rahimi, H., Xing, L., Wood, R. W., Bingham, C. O., 3rd, Ritchlin, C. T., & Schwarz, E. M. (2018). Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis. Nature reviews. Rheumatology, 14(2), 94–106. https://doi.org/10.1038/nrrheum.2017.205

Schwartz, N., Chalasani, M. L. S., Li, T. M., Feng, Z., Shipman, W. D., & Lu, T. T. (2019). Lymphatic Function in Autoimmune Diseases. In Frontiers in Immunology (Vol. 10). Frontiers Media SA. https://doi.org/10.3389/fimmu.2019.00519

U.S. Department of Health and Human Services. (2023, March 3). Overview of Rheumatoid Arthritis. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Retrieved from https://www.niams.nih.gov/health-topics/rheumatoid-arthritis

Kaitlyn Ashburn

April 25, 2023 at 8:06 pm 1 year ago

2 Comments

Attached is my written statement for my STEAM Project:

I chose to do my research and project on the objective of the role of the lymphatic system in the immune response. To go beyond what we learned in class, I researched the autoimmune disorder, Rheumatoid Arthritis (RA), and how it is related to a dysfunctional immune system and the relationship to the lymphatic system. I chose to draw an infographic comparing a normal joint and a joint with RA and additionally including information about the lymphatic and immune functions for each. According to the Arthritis Foundation, “Rheumatoid Arthritis (RA) causes joint inflammation and pain. It happens when the immune system doesn’t work properly and attacks the lining of the joints, called the synovium”. Joints swell in rheumatoid arthritis because of improper drainage of lymphatic fluid.

The lymphatic system and immune system work closely together to protect the body from pathogens. The lymphatic system is the system of vessels, cells, and organs that carries excess fluids to the bloodstream and filters pathogens from the blood. The lymphatic system drains fluids from the body and returns them back to the bloodstream. It drains the excess fluid and empties it back into the bloodstream via a series of vessels, trunks, and ducts. The lymphatic system also has small bean-shaped organs throughout the body called the lymph nodes. The immune system uses lymph nodes as major areas of development for immune response. Immune system cells also use lymphatic vessels to make their way from interstitial fluid back into the circulation.

Rheumatoid arthritis is an autoimmune disorder where immune cells cause inflammation in the synovium. This inflammation becomes chronic, and the synovium thickens due to an increase of cells, production of proteins, and other factors in the joint, which can lead to pain, redness, and warmth. As RA progresses, the thickened and inflamed synovium pushes further into the joint and destroys the cartilage and bone within the joint (Overview of Rheumatoid Arthritis, 2023). Though there is no cure for RA, there are a variety of treatments. One of which is targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis. A study published in 2018 done by researchers from University of Rochester School of Medicine and Johns Hopkins University observed in their research, “that lymphatic drainage increases at the onset of inflammatory-erosive arthritis but, as inflammation progresses to a more chronic phase, lymphatic clearance declines and both structural and cellular changes are observed in the draining lymph node. Specifically, chronic damage to the lymphatic vessel from persistent inflammation results in loss of lymphatic vessel contraction followed by lymph node collapse, reduced lymphatic drainage, and ultimately severe synovitis and joint erosion” (Bouta et al., 2018). As the immune system fails with this autoimmune system, the lymphatic system’s functionality also declines. The study concluded that lymphatic treatment during the “collapsed phase” of lymphatic function may be a viable treatment option for preventing joint inflammation with inflammatory arthritis. This conclusion was made based on “Murine models [that] demonstrated that dramatic changes in lymphatic vessel function occur during the pathogenesis of inflammatory arthritis; these changes include an initial compensatory expanding phase in which the lymph node expands in size and lymphatic contraction and clearance are proficient, followed by a collapsed phase in which lymph nodes decrease in volume and there is a loss of the intrinsic lymphatic contraction. This dichotomy is mirrored by joint inflammation, where knee inflammation is not apparent until the collapsed phase, suggesting that targeting lymphatic function could be a potential treatment option and a promising area for future research”. In my infographic, I summarized the two stages of alterations to lymphatic function in RA. A more detailed explanation of the autoimmune disorder’s effect on the lymphatic system is “that together with the joint inflammation occurring in RA, the local lymphatics undergo two stages of alterations. As a response to the initial, pre-arthritic, synovial inflammation, the lymphatics undergo an “expansion phase,” whereby they increase their capacity to remove excess cellular debris and inflammatory cells from the site of inflammation; whether by lymphangiogenesis, or by increased lymphatic vessel contraction frequency. This process is important to allow for the resolution of the inflammatory process; if the expansion process is stunted, by inhibition of lymphangiogenesis for example, the joint inflammation becomes more severe and clinical synovitis develops. Beyond the lymphatic vessel changes, the draining lymph nodes themselves increase in size during the expansion phase, likely due to increased volume and pressure of fluid within the afferent vessels , intra-nodal lymphangiogenesis and infiltration of a unique subtype of IgM+CD23+CD21hiCD1dhi B cells found in inflamed lymph nodes, known as Bin cells” (Schwartz et al., 2019).

The immune system and the lymphatic system are deeply intertwined with each other to protect the body from pathogens. In the case of RA, this relationship is highlighted by the dysfunction of the immune system resulting in a decline of function in the lymphatic system. The relationship between the two systems is also revealed by a potential treatment for RA being to target the lymphatic system to treat the autoimmune disorder.

Word Count: 869

References

Bouta, E. M., Bell, R. D., Rahimi, H., Xing, L., Wood, R. W., Bingham, C. O., 3rd, Ritchlin, C. T., & Schwarz, E. M. (2018). Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis. Nature reviews. Rheumatology, 14(2), 94–106. https://doi.org/10.1038/nrrheum.2017.205

Schwartz, N., Chalasani, M. L. S., Li, T. M., Feng, Z., Shipman, W. D., & Lu, T. T. (2019). Lymphatic Function in Autoimmune Diseases. In Frontiers in Immunology (Vol. 10). Frontiers Media SA. https://doi.org/10.3389/fimmu.2019.00519

U.S. Department of Health and Human Services. (2023, March 3). Overview of Rheumatoid Arthritis. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Retrieved from https://www.niams.nih.gov/health-topics/rheumatoid-arthritis

Kaitlyn Ashburn

April 25, 2023 at 8:06 pm 1 year ago
The objective being covered in this STEAM project is “Explain the role of the lymphatic system in the immune response.” This piece of work that was created reflects this objective very well. This diagram shows both a knee with and without rheumatoid arthritis, and how the immune function and lymphatic function work with it. The diagrams are drawn very well and clearly show a difference in the two types of knees. In a normal joint, the lymphatic system drains the leaked lymph back into the bloodstream to balance liquids. While in the RA joint it can get to the point where draining fluids is nearly impossible. In a healthy knee, there is very little immune support. Whereas in the RA knee, the immune system will release t cells, b cells, and macrophages to the joint, which can damage nearby bone structure pretty badly. In a normal knee, there is no inflammation, whereas in the RA knee it is just the opposite.

Dawson Freeman

April 25, 2023 at 11:47 pm 1 year ago

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