Tailoring Autoimmune Treatment with Precision Medicine
Precision medicine is a new medical approach designed to tailor disease treatment to people. Not everyone responds to therapy or prevention in the same manner, so medical care should be adapted to patients’ unique characteristics and needs. The aim is to move away from traditional “one-size-fits-all” approaches and shift toward methods that consider individual responses to treatment. Developing precision medicine may improve patient care in all areas of medicine, but the approach may especially benefit diseases with intricate underlying biologic and genetic features.
How Can Precision Medicine Improve Autoimmune Treatment?
Autoimmune diseases are extremely diverse and may fit both chronic and rare disease categories. Their diagnosis or classification is unpredictable; signs and symptoms can be misleading, and responses to medications may vary from person to person.
“I hope the one-size-fits-all approach will be limited to the first half, if not the first quarter of the 21st century”, says Sarah Ennis, PhD, Professor of Genomics at the University of Southampton in the UK.
“By knowing patients’ genetic information, we can match a specific mutation or molecular problem to a drug that targets that problem.”
Benefits of precision medicine for autoimmune diseases include:
- Using people’s genetic or cellular information to design targeted therapies
- Using targeted therapies to treat diseases precisely and minimize toxic side effects
- Reducing trial-and-error drug prescription
- Predicting what treatment will work best for patients with rare diseases
- Selecting ideal therapy administration times
- Increasing patient adherence to prescribed medication
- Improving overall clinical outcomes
What Factors Influence Precision Medicine in Autoimmunity?
Lupus expert Marta Alarcón Riquelme, MD, PhD, Professor and Scientific Director at the new Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO) in Spain, notes that research can be quite a challenge due to the intricate nature of deciphering the relationship between various factors involved in autoimmunity.
“Genetic studies have allowed us to move forward because precision medicine technology has advanced so much,” says Alarcón Riquelme. “But studying the role of environmental factors, diet, and infection is difficult and time-consuming. And studying lupus triggers is especially challenging because of its multisystemic and unpredictable nature.”
What Tools and Technologies Make Precision Medicine Possible?
The area of precision medicine relies on “omics” (for example, genomics and proteomics), technologies that are integrated with other tools, including population genetics, to help identify molecular information about people’s genes or cells. Learning this information will enable the design of interventions that precisely and efficiently act against autoimmunity, replacing trial-and-error approaches that may be ineffective and cause adverse effects.
Ennis specializes in whole-exome sequencing to identify rare mutations in the genes of patients with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis. (1, 2).
“The diseases we label as psoriasis, arthritis, or IBD are ‘mixed bags’ of complex disease that may be triggered by the interaction between genetics and environmental factors. However, some rare autoimmune conditions are driven by one gene that may be masquerading as a complex disease,” explains Ennis.
“Some patients are diagnosed with either ulcerative colitis or Crohn’s disease, but their condition may be caused by an underlying malfunction in a single gene. For example, identifying a rare genetic mutation called XIAP led to a young boy’s complete recovery after receiving a stem cell transplant. If doctors had observed the boy’s signs and symptoms alone, they may have diagnosed him with severe, early-onset Crohn’s disease and prescribed medications that may not have been effective.”
What Are the Challenges of Applying Precision Medicine to Autoimmune Disease?
Dr. Alarcón Riquelme discussed the challenges of using precision medicine in autoimmune disease, especially for lupus (3).
“Because some autoimmune diseases are especially insidious, identifying them can take a long time,” says Alarcón Riquelme. “And for lupus, we have classification criteria that rely on markers, such as antinuclear antibodies, which are also observed in asymptomatic individuals. Therefore, it is important to predict who among these individuals will eventually develop lupus. One approach is to closely monitor people who tested positive for specific markers and catch early signs of disease, so we can act quickly.”
Although genetic testing is one of the promising tools of precision medicine, Alarcón Riquelme believes that its usefulness greatly depends on the disease.
“Through genetic testing, we may identify lupus risk variants in research settings, but we cannot always guarantee that the findings can be applied to real-world situations,” says Alarcón Riquelme. “Also, patients may want to learn about their personal risk of developing the disease, but should consider whether they are prepared to live with that knowledge, particularly when treatment options are limited,” she adds. “For lupus, knowing the family history and following patients to anticipate severe outcomes are still essential.”
Ennis emphasizes the importance of genomic studies but also highlights the challenges of data analysis.
“Our genomic studies generate enormous sets of data with millions of genetic variants. So, we are always trying to find ways to collapse the data and select the most important signals, which isn’t easy,” she says. “We have the various ‘omics’, but we also need to better integrate them with one another and develop methodologies that will help us spot patterns in data.”
What Ethical Concerns Come With Precision Medicine Research?
Ethical considerations in conducting precision medicine research for autoimmune diseases include:
- Genetic testing privacy
- Data security
- Identity protection
- Healthy control testing
“Genetic data holds sensitive information, including ethnicity and disease susceptibility, so it needs to be handled carefully,” explains Ennis. “We have secure systems in place, but scientists are not especially good at explaining these concepts, so we need to have more conversations.”
Ennis mentions that because people with rare diseases are fewer in number, their distinct phenotypes, the set of observable features of an individual, might make them more recognizable.
“We need to protect one’s identity when we share results,” Ennis adds, “but patients with rare diseases have long been underserved and need hope and answers. So, we need to find ways to balance innovation and ethics.”
Additionally, studies involving healthy individuals are challenging to conduct. “In our IBD studies, we have observed that healthy people with rare disease variants may have other mutations that ‘rescue’ that variant. While this is promising, ethics committees may not easily allow samples to be collected from healthy people because the tests are too invasive,” says Ennis.
How Can Precision Medicine Shape the Future of Autoimmune Care?
Both experts highlight that progress in precision medicine requires the work of multidisciplinary teams to solve complex problems and overcome disparities.
“Patients with autoimmune diseases can have multiple complications and, sometimes, overlapping illnesses, so they are often followed by various specialists,” says Alarcón Riquelme. “Communication across specialties is essential to manage both autoimmune diseases and comorbidities. And more collaborations should be established between hospitals and universities across countries.”
“We need new methodologies to analyze large sets of genomic data, so we are actively recruiting experts in machine learning who sit at the interface of computer science and healthcare data applications,” adds Ennis. “We also need mathematicians, biologists, clinicians, and ethicists.”
Alarcón Riquelme also mentions barriers to access. “We need to work toward addressing health disparities related to race and socio-economic status.”
About the Author
A freelance writer who specializes in medical and life science topics. As a trained researcher, she authored journal articles in the areas of infection and immunity and wrote booklets and book chapters about different diseases. As a professional communicator, she writes feature articles for magazines and other publications and develops content for higher education platforms. Damiana is also an experienced academic editor, microbiology educator, writing coach, and fragrance blogger. She is a contributing member of the American Medical Writers Association and a past-president of the association’s Southwest Chapter.
Sources
- Article Sources
Stafford I.S., Kellerman M., Mossotto E., Beattie R.M., MacArthur B.D., & Ennis S. (2020). A systematic review of the applications of artificial intelligence and machine learning in autoimmune diseases. NPJ Digital Medicine. 10.1038/s41746-020-0229-3. https://pubmed.ncbi.nlm.nih.gov/32195365/
Stafford I.S., Ashton J. J., Mossotto E., Cheng G, Beattie R.M., & Ennis S. (2023). Supervised Machine Learning Classifies Inflammatory Bowel Disease Patients by Subtype Using Whole Exome Sequencing Data. Journal of Crohn’s Colitis. 17(10):1672-1680. https://pubmed.ncbi.nlm.nih.gov/37205778/
Toro-Dominguez D. & Alarcon-Riquelme M. (2021). Precision medicine in autoimmune diseases: fact or fiction. Rheumatology. 60(9):3977-3985. https://pubmed.ncbi.nlm.nih.gov/34003926/
