Researchers have long known that lupus and other autoimmune disorders tend to run in families. However, the inheritance pattern is in most cases unknown. And not everyone who inherits a gene variation that increases the chance of developing lupus, will develop lupus. That is why genetics of lupus is a key area of research.
Over the last decade we have learned a lot about how our genes affect lupus development. The goal is to one day be able to predict an individual’s risk for lupus by studying their genes and have a treatment plan which can modify or even prevent the person from developing lupus.
What role the genetics of lupus plays and what one can do and not do about it has become a hot topic of research. In his keynote lecture on Thursday, Jean-Laurent Casanova, MD, PhD, Professor at the Howard Hughes Medical Institute and Senior Attending Physician at Rockefeller University addressed the role of genetics and lupus in pediatric populations. The goal of Dr. Casanova’s research to understand why some children, adolescents, and young adults develop a severe clinical illness in the course of infection, while most people exposed to the same microbe remain unharmed.
Dr. Casanova has identified inborn errors of immunity (primary immunodeficiencies we are born with) that lead to an increased susceptibility to a variety of pathogens in children. Examples include the discovery of a molecular genetic basis that causes a predisposition to mycobacterial disease and invasive pneumococcal disease. Dr. Casanova said primary immunodeficiencies play a role in the development of lupus as well. “These primary immunodeficiencies in young people causes severe and selective vulnerability to certain infectious illnesses during primary infection which has implications for autoimmune illnesses such as lupus.”
Edward Wakeland, PhD, Professor of Immunology University of Texas Southwestern Medical Center spoke on current and future directions of lupus genetics and the need to utilize the tools of precision medicine to better understand and treat lupus.
Dr. Wakeland said precision medicine, which tailor’s medical treatment to the individual characteristics of each patient, shows great promise in lupus. “Precision medicine has had great success in cancer treatment. In the future, I believe precision medicine will lead to tailored treatments for specific patients with lupus.”
He explained that the antinuclear antibody (ANA) test is commonly used to look for autoantibodies that attack components of a cells’ nucleus, or “command” center, triggering autoimmune disorders like lupus. Dr. Wakeland said, “autoimmunity is a common trait in humans and is detectable in both ANA positive and negative individuals. However, patients with lupus have a significant increase in autoantibody levels, compared to non-lupus patients.”
Dr. Wakeland studied 773 patients which he divided into four subgroups based on their genomic variants. “By determining the disease pathologies and immune system features of each lupus cluster, we are taking a key step in the development of companion diagnostics for lupus patient therapy and disease management.”
The panelists agreed that it is unlikely that a single biomarker will ever be able to define the response to therapy and prognosis in lupus. Like cancer and heart disease, the lupus community need to use traditional and new biomarkers, as well as best clinical practices to bring precision medicine to the treatment of lupus.
