Autoimmune diseases are defined as chronic conditions that occur when the immune system launches an attack against its cells (Anaya, 2010). In other words, they happen when the immune system loses tolerance to the body’s recognition molecules, self-antigens. Their categorisation often hinges on the site of inflicted damage; for instance, when singular organs are targeted, they are termed organ-specific diseases, whereas the involvement of multiple organs denotes a systemic condition.
The primary focus of this article is autoimmune disorders, with special attention given to the innovative findings presented in Gupta's (2023) groundbreaking study, along with additional insights into dynamic regulatory components. By investigating inflamed synovial tissue using a combination of multimodal single-nucleus RNA sequencing and ATAC sequencing techniques, profound understandings have been gained regarding the cellular states intricately associated with autoimmune conditions like rheumatoid arthritis.
This focus is important because understanding the dynamic regulatory elements in these diseases is a crucial step toward developing targeted and curative therapies. Concentrating on better understanding gene expression patterns and chromatin accessibility enhances our understanding of autoimmune diseases, potentially opening avenues for personalised and efficient treatment approaches.
However, let’s refer our attention to a fundamental question:what triggers autoimmune diseases? Despite extensive scientific investigation, a conclusive answer remains elusive, though numerous theories have emerged to address this issue. Some suggest a correlation between infections and autoimmune diseases (Orbai, 2019), proposing that certain healthy cells may inadvertently become targets of the immune system's assault. Others theorize that accidents and various forms of trauma could instigate an autoimmune response. Nevertheless, common threads among all researchers include the roles of genetics and environmental factors in the development of autoimmune conditions. While genetics may predispose individuals to autoimmune disorders, some studies indicate instances where individuals possess the genetic markers for a specific autoimmune condition but do not manifest the condition itself. Furthermore, investigations involving identical twins have demonstrated that despite sharing identical genetic makeup, one twin may have the condition while the other does not, suggesting the influence of environmental factors.
A recent investigation by Sukeinova et al. (2024) explored Guillain–Barré syndrome (GBS), an autoimmune disorder impacting the peripheral nervous system. GBS manifests when there is damage to either the myelin sheath or the nodes of Ranvier, resulting in potential respiratory complications, muscle weakness, paralysis, and sensory impairments. While the precise etiology of this condition remains uncertain, speculation suggests a potential association between GBS and SARS-CoV-2, aligning with earlier hypotheses proposed by other researchers
In the field of autoimmune diseases, researchers navigated through the complexities of the immune system. A study led by A. Gupta and colleagues entailed a comprehensive analysis employing multimodal single-nucleus RNA and ATAC sequencing techniques, encompassing a remarkable 28,674 cells extracted from inflamed synovial tissue. This multidimensional approach unveiled the complexities of gene expression patterns and offered an unprecedented understanding of the dynamic interplay between chromatin accessibility and immune responses. From my perspective, focusing on genetic-level insights is crucial for advancing knowledge to aid a larger population of sufferers through personalized treatments and medications (Gupta et al., 2023).
Figure 1. A 3D model of the tn5 transposase enzyme used in ATAC sequencing. Image source: https://sciencephotogallery.com/featured/transposase-enzyme-and-dna-complex-laguna-design.html
As there are no cures for autoimmune diseases, the quality of life for afflicted individuals is significantly compromised. Globally, approximately 10% of the population is affected by these diseases, contributing to high healthcare expenses. Presently, the annual global expenditure on autoimmune disease management amounts to $149 billion, a figure that could potentially decrease with the advent of new scientific breakthroughs aimed at treating and possibly eradicating these ailments.
Among the over 100 autoimmune diseases, Type 1 diabetes and Rheumatoid arthritis stand out as two of the most prevalent (Gillespie, 2006). For instance, Type 1 diabetes causes the destruction of insulin-producing beta cells by the immune system, leading to organ damage, particularly in the kidneys and eyes. Symptoms include frequent urination, excessive thirst, blurred vision, and unintended weight loss (Gillespie, 2006).
(Willyard, 2024). On the other hand, Rheumatoid arthritis, a chronic inflammatory disorder, targets the synovial lining of joints, leading to pain, stiffness, and progressive joint destruction. The immune system mistakenly attacks healthy tissue, triggering inflammation that can spread to other organs, including the heart and lungs. Individuals with Rheumatoid arthritis often endure debilitating symptoms that significantly impact their mobility and overall quality of life.
Both Type 1 diabetes and Rheumatoid arthritis underscore the significant impact autoimmune diseases have on individuals' health and well-being, emphasizing the urgent need for effective treatments and interventions to alleviate suffering and improve outcomes.
However, there is optimism for the development of future treatments that to the research of scientists worldwide, exemplified by the efforts at the University of Calgary in Canada under the guidance of Dr. Santamarina. (Willyard, 2024) Dr. Santamarina's breakthrough involves targeting the specific immune cells responsible for initiating autoimmune attacks. The objective is to develop medications that exclusively pinpoint these cells, thereby eliminating them. This approach holds promise for minimizing side effects since a larger pool of immune cells would remain, thereby reducing the susceptibility to infections. Another option involves restoring the body's tolerance against self-attack, which could be achieved through the use of antigens.
Figure 2. Image showing how engineered cells that produces antibodies (CAAT T cell) would target the cells that produce harmful autoimmune antibodies, triggering their death. Image source: https://www.nature.com/articles/d41586-024-00169-7
In summary, autoimmune diseases entail the body's immune system mistakenly attacking its own tissues. While the precise cause remains elusive, factors such as genetics, environmental influences, infections, and injuries contribute to this phenomenon. Approximately 10% of the global population experiences at least one type of autoimmune condition, with examples including Type 1 diabetes, Rheumatoid Arthritis (RA), and Guillain–Barré Syndrome (GBS). Current scientific advancements offer promising prospects, suggesting new medications as potential remedies. With the advancement of research, there is confidence that we will approach closer to discovering cures for these conditions, ultimately improving the well-being of those affected. This article is written by Eneos Rapousai, Brunel University, London, UK.
References
1. Gupta, A., Weinand, K., Nathan, A., Sakaue, S., Zhang, M.J., Donlin, L., Wei, K., Price, A.L., Amariuta, T. and Raychaudhuri, S. (2023). Dynamic regulatory elements in single-cell multimodal data implicate key immune cell states enriched for autoimmune disease heritability. Nature Genetics, [online] 55(12), pp.2200–2210. doi: https://doi.org/10.1038/s41588-023-01577-7
2. Orbai, A.-M. (2019). Autoimmune Disease: Why Is My Immune System Attacking Itself? [online] Johns Hopkins Medicine. Available at: https://www.hopkinsmedicine.org/health/wellness-and-prevention/autoimmune-disease-why-is-my-immune-system-attacking-itself
3. Súkeníková, L., Mallone, A., Schreiner, B., Ripellino, P., Nilsson, J., Stoffel, M., Ulbrich, S.E., Sallusto, F. and Latorre, D. (2024). Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome. Nature, [online] pp.1–9. doi: https://doi.org/10.1038/s41586-023-06916-6
4. Willyard, C. (2024). Can autoimmune diseases be cured? Scientists see hope at last. Nature, [online] 625(7996), pp.646–648. doi: https//doi.org/10.1038/d41586-024-00169-7