The period between the onset of asymptomatic autoimmunity and the development of symptomatic disease is referred to as “pre-clinical” autoimmunity, as the appearance of autoantibodies precedes most autoimmune diseases. Most patients with autoimmune disease only develop symptoms after abnormal immune reactions begin (1). Pre-autoimmunity has been observed in several autoimmune diseases, including Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sjögren’s Syndrome, Primary Biliary Cirrhosis, Inflammatory Bowel Disease (Crohn’s Disease and Ulcerative Colitis), and Multiple Sclerosis (2).
The mechanisms of autoimmunity occur when the immune system attacks its host. Autoimmune diseases are largely thought to occur from immune dysregulation, and while there is currently no way to prevent someone from developing an autoimmune disease, there are promising advancements in scientific discovery.
Recently, “scientists identified a new type of human T cell that quells assaults on healthy tissues” (3). T cells (specifically those distinguished by the surface protein CD8), previously known for killing infected or cancerous cells, were found to kill other T cells that orchestrate autoimmune reactions in mice. The existence of CD8 T cells in humans is now confirmed.
Separately, a team at Johns Hopkins is looking for solutions at the cellular level by using a protein that activates and increases the number of special, regulatory T cells that can stop autoimmune disease development. “The molecule, which fuses the interleukin-2 cytokine and the anti-cytokine antibody F5111, promoted T cell activation and expansion and protected non-obese diabetic mice against autoimmune disease development to a statistically significant degree,” an article from Johns Hopkins explained.
Researchers at the Walter and Eliza Hall Institute also identified an enzyme that appears to prevent autoimmune diseases. An enzyme in the thymus, KAT7, was found to be necessary to activate thousands of genes needed for “training” immune T cells not to attack healthy tissue. The research “paves the way for potential treatments to target KAT7, which could modify the training of immune T cells as needed.”
The average autoimmune disease diagnosis takes four years from the onset of symptoms.
Diagnosing autoimmune diseases can be difficult because there is no one specific autoimmune disease test.
Many autoimmune diseases also exhibit symptoms that are common to other conditions, such as muscle aches and a low-grade fever (4). To diagnose an autoimmune disease, a patient must have specific symptoms combined with specific blood markers and, in some cases, even a tissue biopsy (5).
Understanding pre-autoimmunity and the development of autoimmunity may offer key insight into the progression of autoimmune diseases.
Immunological and metabolic pathways are one of the most hopeful ways to find specific and early interventions at the individual patient level, and there is currently a plethora of research focused on pre-clinical autoimmunity across a number of conditions (9).
One research team at Boston Children’s Hospital, funded by The Global AutoImmune Institute, uses blood samples to simultaneously test for multiple autoantibodies associated with many different autoimmune conditions using autoantigen microarray panels. Utilizing this technology, the team will investigate whether there are identifiable autoantibody signatures that can distinguish individuals who have only one autoimmune condition from those who have multiple.
The hope is to discover biomarkers that can be used to identify individuals who are at risk of polyautoimmunity prior to their development. The team will then use these findings to develop a standardized approach to screen and care for patients with multiple autoimmune conditions.
Rosenblum, M.D., Remedios, K.A. and Abbas, A.K. (2015) Mechanisms of human autoimmunity. The Journal of Clinical Investigation, American Society for Clinical Investigation.
Hu, Z.-D. and Deng, A.-M. (2014) Autoantibodies in pre-clinical autoimmune disease. Clinica Chimica Acta. Elsevier.
Leslie, M. (2022) New class of killer T cells may prevent autoimmune diseases. Science. doi: 10.1126/science.adb1862
Autoimmune diseases | MedlinePlus. U.S. National Library of Medicine.
What are common symptoms of autoimmune disease? (2022) Johns Hopkins Medicine.
C-Reactive Protein (CRP) test: MedlinePlus medical test. MedlinePlus. U.S. National Library of Medicine.
Erythrocyte sedimentation rate (ESR): MedlinePlus Medical Test. MedlinePlus. U.S. National Library of Medicine.
ANA (antinuclear antibody) test: MedlinePlus medical test. MedlinePlus. U.S. National Library of Medicine.
Karp, D., Holers, V.M., Okuda, D., Olsen, N. (2022) Understanding the concept of pre-clinical autoimmunity. Frontiers.