Akiko Iwasaki, PhD: Exploring the Drivers of Lupus via Endogenous Retroviruses

Akiko Iwasaki, PhD, was awarded Lupus Research Alliance’s Lupus Insight Prize (LIP) for her research into the potential causes of lupus, discovering a link between systemic lupus erythematosus (SLE) and endogenous retroviruses. Findings suggest that identifying ways these retroviruses impact inflammation in this condition may lead to new therapeutic options for patients with this condition, as well as potentially uncover a connection between COVID-19 and other autoimmune diseases. Iwasaki is the Sterling Professor of Immunobiology and Professor of Dermatology and Molecular, Cellular, and Developmental Biology and of Epidemiology at Yale School of Medicine, and an Investigator at the Howard Hughes Medical Institute,

“The $100,000 award recognizes and honors an outstanding investigator who has, within the past 5 years, published a novel and important research insight into lupus that advances our understanding of this disease and could open new avenues for lupus diagnosis and treatment,” the press release noted.

Iwasaki and her team analyzed 3220 unique sequences of endogenous retroviruses, genetic segments of retroviral origin that make up approximately 8% of the human genome, to understand which retroviral sequences are elevated in immune cells of lupus patients that couldcause or worsen this disease. After developing a human endogenous retrovirus map (ERVMap), the team found that over 100 segments were strongly elevated in the peripheral blood mononuclear cells of patients with lupus. These elevated levels were linked to an increased type-1 interferon levels, which are considered to be a main driver of lupus. Additionally, patients with lupus were more likely to produce autoantibodies that target the HERV-K102 protein, which worsens inflammation in SLE.

"Dr. Iwasaki's research shows that endogenous retroviruses are not just silent inhabitants in the human genome but rather active players able to provoke immune cells to engage in the destruction of the body's own tissues and organs,” Judith James, MD, PhD, LRA Scientific Advisory Board member, stated. “This finding is highly significant because endogenous retroviruses have been increasingly associated with several chronic diseases including cancer, neurodegenerative, and autoimmune rheumatic diseases, though their exact role in human diseases remains poorly understood.”