Thromboinflammatory Consequences of Infection-Induced Autoimmunity

November 9, 2022
Yu (Ray) Zuo, MD, MSCS
Yu (Ray) Zuo, MD, MSCS

Yu (Ray) Zuo, MD, MSCS, Assistant Professor in the Division of Rheumatology and co-lead of the Antiphospholipid Syndrome Research Labs, received a Career Development (K08) Award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) to investigate the thromboinflammatory consequences of infection-induced autoimmunity.

"A growing body of evidence suggests that COVID-19 emulates many aspects of inflammatory and autoimmune diseases," said Dr. Ray Zuo. "Circulating autoantibodies have been detected in the serum of COVID-19 patients where they have an antigen profile reminiscent of the lupus-associated thrombophilia known as antiphospholipid syndrome."

"While the association between infection, critical illness, and the induction of autoantibodies has long been recognized, the pathogenesis and persistence of these antibodies - and most importantly the extent to which they may be therapeutic targets - have not been well defined."

Learn more about Dr. Zuo's research and what he hopes to achieve

What are the aims of your research?

I plan to use COVID-19 and other severe infections as a window into the origins of autoimmunity and, in doing so, determine thromboinflammatory mechanisms of infection-associated autoantibodies.

  • Aim 1: To elucidate the durability and clinical interactions of antiphospholipid antibodies and anti-NET antibodies in patients hospitalized with either COVID-19 or non-COVID sepsis
  • Aim 2: To characterize the pathogenic and protective functions of infection-associated autoantibodies

How will this research support your long-term career goals?

This award will play a critical role in helping me achieve my long-term career goals, which include:

  • Establishing a unique niche in the area of infection-associated autoimmunity
  • Becoming an independent investigator at a leading medical research institution
  • Mentoring and fostering the development of trainees.

These objectives will be reached by incorporating both a strong mentorship environment and a formal instructional plan.

What do you hope to achieve with this study? 

Successful completion of this study will provide new insights into the role of infection in de novo autoantibody production. At the same time, it will lay the groundwork for a future R01 proposal to comprehensively understand the differentiation and function of autoantibody-producing B-cell subsets in acute, serious infections. Furthermore, this proposal is likely to reveal new aspects of APS/lupus immunopathogenesis, while also potentially identifying new treatment targets for COVID-19.

Finally, this proposal will be a platform whereby I will receive mentored and didactic training and gain the required skills to ensure my development into an independent translational investigator with a niche in the area of infection-associated autoimmunity and its downstream consequences.