by Dr. Chase Spurlock, IQuity CEO and Dr. Thomas Aune, IQuity Chief Science Officer
Diagnosing complex autoimmune diseases and related conditions is a challenging endeavor, as these multifaceted conditions often present with non-specific symptoms across several organ systems. Historically, physicians have diagnosed autoimmune disease through detailed physical examination, collection of medical and family history, multiple laboratory tests and monitoring symptoms over time. Current diagnostic algorithms can lead to a protracted and costly diagnostic process of elimination.
However, emerging RNA-based diagnostic technologies can dramatically reduce the time to diagnosis of complex diseases, including autoimmune disease. With the completion of the Human Genome Project and basic research in the field of RNA biology over the past two decades, it is now accepted that the majority of the human genome is transcribed into unique patterns of information that exhibit cell type specificity and are consistent in a variety of chronic conditions, including autoimmune disease. With the invention of new technologies, including next-generation RNA sequencing, we are able to assess global changes in gene expression.
As such, RNA-based tools are now poised to provide physicians with actionable information early in the diagnostic process. While RNA-based testing is a relatively new innovation in the clinical setting and widespread adoption efforts are still in their infancy, the science behind these techniques makes them a reliable method for helping physicians make fast, accurate decisions.
The science behind RNA
Analysis of RNA expression paints a molecular portrait of what’s going on in an individual’s cells at a given point in time. This can provide a picture of disease manifestation. At a high level, current RNA testing involves collecting a patient’s blood sample via standard venipuncture, isolating the RNA and then detecting RNA expression patterns in real time using polymerase chain reaction (PCR). The turning on or off of these expression patterns can serve as an indicator of the presence or absence of disease.
In contrast, DNA tests examine changes in nucleotide sequence to establish a patient’s risk of developing a particular condition. These genotype associations do not always reveal information about disease manifestation. A DNA test, for example, might indicate that a patient is at high risk for an autoimmune disorder, such as rheumatoid arthritis (RA) or multiple sclerosis (MS), but the patient may never develop the condition. Just because the patient has a particular DNA risk marker does not mean he or she actually has—or will have—the disease. Thus, a major limitation with DNA methodology is its inability to reliably forecast active disease. RNA tests are more specific in this regard.
Other types of testing, such as pharmacologic and serologic testing, have also been used to detect autoimmune disorders. However, due to the complexity of these diseases, a single test can only put a physician one small step closer to diagnosis and additional tests are often required. For instance, to accurately identify RA, a clinician may need to perform approximately 10 to 15 different molecular tests over what is often a lengthy time period. If the doctor concludes that a portion of these tests point to the presence of RA, then he or she may be able to make a diagnosis of RA. In some cases, it can take years for the patient to receive a definitive diagnosis. In comparison, new RNA-based diagnostic testing for the same condition offers an accuracy of greater than 90 percent, enabling a higher degree of certainty for establishing the presence or absence of the disease.
The impact on patients, providers and the scientific community
As RNA testing becomes more widespread, its impact on patients, providers and other stakeholders promises to be significant. Once widely adopted, this kind of testing could cut down on the number of tests and amount of the time needed to confirm diagnosis. This, in turn, would enhance the patient experience, as individuals would no longer have to undergo repeated or invasive testing to determine if they have a disease.
Current autoimmune therapies are reasonably effective at slowing disease advancement. Across many autoimmune diseases, the best outcomes are achieved when therapies are initiated early in the disease process. Providing physicians with actionable diagnostic information enables the provider to place patients on the appropriate treatments faster, limiting disease progression and supporting better long-term health outcomes.
RNA testing can improve outcomes for providers by helping to get patients on the path to suitable treatment earlier. This not only facilitates optimal medication performance, but also lessens the cost of diagnosis and management of disease. In turn, this ensures a better quality of life for patients.
About the Authors
Chase Spurlock, IQuity CEO
Through combined experiences in the laboratory and clinic, Dr. Spurlock is committed to translating basic science discoveries into improved diagnostic strategies for patients with autoimmune conditions. Dr. Spurlock’s published work explores the molecular basis for autoimmune disease and further examines therapeutic targets in the management of these diseases leveraging a diverse set of genomic and biochemical approaches including gene expression and next-generation sequencing technologies. Dr. Spurlock is a Phi Beta Kappa graduate of The University of the South where he received his bachelor’s degree in biology. He earned his Ph.D. in microbiology and immunology from Vanderbilt University School of Medicine, where he was awarded the Sidney P. Colowick award for outstanding research and continues to serve on the faculty.
Dr. Thomas Aune, IQuity Chief Science Officer
As Chief Scientific Officer, Dr. Aune is responsible for driving innovation in the science, facilitating test development, and ensuring quality control. His current research focuses on the use of functional genomic and epigenetic approaches to understand gene regulation; these interests range from detailed mechanistic studies of the interferon-gamma gene, a key cytokine produced by cells of the innate and adaptive immune system required to induce cell-mediated inflammation to the use of these approaches to fain new insights into human disease, including efforts to develop new diagnostic tests for autoimmune diseases. After receiving his Ph.D. from the University of Tennessee, Dr. Aune pursued postdoctoral training at Stanford and Washington University in St. Louis. He has served on the faculty at Washington University in St. Louis and Vanderbilt University School of Medicine where he is currently a full professor. Dr. Aune also worked at Genentech and then at Bayer where he led the immunology division.