Writer: Josue Navarro ‘25
Editor: Jason Johnston '23
Image 1. Ankylosing Spondylitis [1].
As medical interventions evolve, diseases are targeted with more specificity to ensure effective treatment while causing minimal damage to the host. The medical field has gone from home remedies to targeted gene-edited treatments, and is now moving toward curing and alleviating symptoms of some of the cruelest diseases known to mankind, like cancer and autoimmune diseases.
One of these diseases is Ankylosing Spondylitis. Ankylosing Spondylitis (AS) is a rare autoimmune disease that causes the fusion of bones and cartilage in the spine as a result of extra bone growth and inflammation [2]. Men ages 20-30 are at high risk for developing AS, but it can also target women [2]. The exact cause of this disease still remains uncertain, however, researchers have been able to piece information regarding the pathogenesis of this disease together to get an idea of what happens. In 90% of AS cases, a mutation is present in the HLA-B27 gene [3]. Human Leukocyte Antigen B27 (HLA-B27) is a protein that forms the Major Histocompatibility Complex (MHC) [4]. This helps the body’s immune system—specifically T killer cells—distinguish between its own cells and foreign ones [3]. A mutation in the gene results in the downregulation of apoptosis in the TH17 cells [3]. This, combined with other factors lead to the instability of the HLA-B27 gene. However, it is important to note that having the mutation will not necessarily lead to AS, which is something scientists are still researching [3]. Additionally, high levels of IL-17 have been found in the serum of patients with AS [3]. IL-17 is an inflammatory cytokine that plays a role in autoimmune diseases by activating T cells and macrophages [5]. Not surprisingly, mounting an immune response when nothing is wrong results in the destruction of healthy cells.
Unfortunately, there is no known cure for Ankylosing Spondylitis. However, there are treatments on the market that help alleviate the symptoms and have the potential to slow the progression of the disease. Current treatments include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), TNF-α inhibitors, and IL-17 inhibitors [3]. These treatments are still being researched, but a challenge that they pose is that they contain small doses of lethal drugs that can be damaging to the patient over time [3]. In order to combat this issue, researchers are exploring new avenues using knowledge acquired in the treatment of other autoimmune diseases.
Nanotechnology-based treatments have been used to treat rheumatoid arthritis and osteoarthritis. There are three treatments that are currently being used: liposomes, polymeric nanoparticles, and hydrogels. Liposomes are phospholipids that are able to hold hydrophobic and hydrophilic drugs. These phospholipids can carry drugs and cytokine inhibitors through the bloodstream that can block inflammatory responses from taking place. Polymeric nanoparticles have been used to deliver drugs to places in which autoimmunity has caused problems. Mainly, working evasion of destruction and clearance of macrophages at joints [6]. Additionally, the very small size of these particles makes it easy to deliver their drugs and helps deactivate immune cells which causes the unwanted response we see in these patients [3]. Hydrogels are also an emerging therapy that has been studied in other autoimmune diseases. Hydrogels are able to hold large amounts of water because of their cross-linking abilities to form a stable vehicle for the transport of fluids [3]. In animal models, hydrogels have been able to decrease the levels of pro-inflammatory cytokines, joint swelling, and joint swelling [3]. Hydrogels are still being studied as they are a new treatment, but studies such as these show anti-inflammatory properties which can help when studying autoimmune diseases.
In the case of ankylosing spondylitis, nanotechnology-based treatments are still being studied. However, understanding the way that treatments have worked in the past can allow us to understand and innovate treatments that can better target autoimmunity. For liposomes, IL-17 inhibitors can be delivered into cells into the spine and cartilage to stop cytokines from recruiting more leukocytes to the supposed “site of infection”. When it comes to polymeric nanoparticles, drugs can be transported to the site of infection to halt strong inflammation. In terms of hydrogels, the delivery of inhibitory cytokines can also be done to prevent strong immune responses from happening. Exploring these nanotechnology-based treatments would allow for a targeted and mediated treatment of AS. Current treatments for autoimmune diseases have very excruciating side effects and may cause serious complications. However, by evolving these treatments, these side effects will be mediated and treatment would be provided as needed.
All in all, autoimmune diseases are complex, and treatments are being studied and developed every day. However, scientists are now using the limited knowledge of other autoimmune diseases to treat, and one day, cure diseases that have poor prognoses.
References
1. Gravis T, Ankylosing Spondylitis [Illustration]. 2020. Weill Cornell Medicine. Brain & Spine Center
2. Xi Y, Jiang T, Chaurasiya B, Zhou Y, Yu J, Wen J, et al. Advances in Nanomedicine for the Treatment of Ankylosing Spondylitis. Int J Nanomedicine [Internet]. 2019;14:8521–42. Available from: http://dx.doi.org/10.2147/IJN.S216199
3. Ankylosing Spondylitis [Internet]. Autoimmune Association. 2015 [cited 2022 Dec 11]. Available from: https://autoimmune.org/disease-information/ankylosing-spondylitis/
4. HLA-B27 Antigen [Internet]. Mount Sinai Health System. [cited 2022 Dec 11]. Available from: https://www.mountsinai.org/health-library/tests/hla-b27-antigen
5. Zenobia C, Hajishengallis G. Basic Biology and Role of Interleukin-17 in Immunity and Inflammation. Periodontol 2000 [Internet]. 2015;69(1):142–59. Available from: http://dx.doi.org/10.1111/prd.12083
6. Carl JW, Bai X-F. IL27: Its Roles in the Induction and Inhibition of Inflammation. Int J Clin Exp Pathol. 2008;1(2):117–23.