ACR Annual Meeting

2021 ACR Convergence

ACR Convergence 2021

The ACR Convergence, an annual scientific meeting hosted by the American College of Rheumatology, is taking place virtually on November 5-9, 2021. Many consider it the world's premier rheumatology meeting, and it is always an honor to be invited for an oral presentation (many aspects of the meeting are presented in poster format). This year, members of our lab family will present six talks, which is a new record for us. See below for a list of our presentations and a brief summary of each.

NETosis in SLE and APS

Presenting Author: Jason S. Knight, MD, PhD
Session: The Many Faces of Cell Death
Date: Saturday, November 6

Dr. Knight has been invited to speak on a type of cell death called NETosis that appears to be important in both lupus and APS. White blood cells called neutrophils “die” and are replaced all the time. Normally this process happens quietly and without stirring up trouble for the immune system, which is a good thing! In contrast, the type of cell death called NETosis is probably designed as an emergency response to stop invading bacteria and viruses. NETosis is not quiet at all and unfortunately happens when it shouldn’t in both lupus and APS. This leads to organ damage and blood clots. The Knight lab made the first description of this phenomenon in APS back in 2015.

Single-Cell RNA Sequencing of APS Skin Reveals Endothelial Pathology & Cellular Interactions

Presenting Author: Hui Shi, MD, PhD
Session: Abstracts - Antiphospholipid Syndrome
Date: Sunday, November 7

This is a super interesting project that we were able to start based on a generous donation to the lab (the donor asked to remain anonymous). We are now in the process of submitting several large grants that we hope will allow us to take the work even further. Dr. Knight has been known to say that “this may be the most important APS project anywhere in the world right now!” As an introduction to the project, we know that blood vessels in the skin of APS patients can be abnormal, which sometimes comes to the surface with a skin change called livedo reticularis. Patients who have livedo are also more likely to have internal organ trouble including in the brain. Using a cutting-edge (and unfortunately very expensive) molecular technique called “single-cell RNA sequencing,” we can turn skin biopsies into a detailed atlas of all the genes expressed by APS blood vessels. Our prediction is that whatever is going wrong with skin blood vessels is also happening in the internal organs. We think this is likely to reveal totally unknown targets for treatment. We can’t wait to go deeper with this project using skin as a window inside APS! Read the abstract here.

Immunometabolism of Neutrophils in APS

Presenting Author: Ajay Tambralli, MD
Session: Abstracts - Antiphospholipid Syndrome
Date: Sunday, November 7

This is another new project that we haven’t published anywhere yet, and one that is in the pilot stage as we try to unlock the funding that will let us make it bigger. Dr. Tambralli has made the observation that APS neutrophils abnormally express a number of genes related to how they process and make energy from glucose (i.e., blood sugar). As compared with other types of white blood cells, neutrophils are super dependent on a constant supply of glucose! We therefore believe these changes could be telling us something fundamental about what is wrong with neutrophils in APS. Put another way, we think that by understanding the what, when, and why of the neutrophil diet, we are likely to identify better markers of smoldering disease activity and likely new targets for therapy. Read the abstract here.

Common Mechanisms of APS & COVID-19

Presenting Author: Jason S. Knight, MD, PhD
Session: Study Group - Antiphospholipid Syndrome and COVID-19
Date: Monday, November 8

Dr. Knight was invited to participate in a round table discussion exploring the intersection of APS and COVID-19. Given Dr. Knight’s particular expertise on the molecular side of both APS and COVID-19 research, he will attempt to untangle similarities and differences in clotting mechanisms between the two diagnoses. This is a very timely topic that he has discussed in several talks this summer:

Autoantibodies Stabilize Neutrophil Extracellular Traps in COVID-19

Presenting Author: Yu (Ray) Zuo, MD
Session: Abstracts - Innate Immunity
Date: Monday, November 8

This is a COVID-19 project led by Dr. Zuo. The project was still in a preliminary state when he submitted his work to the meeting this summer, but it has now been turned into a full publication. Read the abstract here.

Endothelium-Protective, Histone-Neutralizing Properties of the Polyanionic Agent Defibrotide

Presenting Author: Hui Shi, MD, PhD
Session: Abstracts - Innate Immunity
Date: Monday, November 8

This exciting project was so much work! Like Dr. Zuo, Dr. Shi submitted her data to the meeting when it was still in preliminary form this summer, but it can now be seen as a final published paper. These experiments were supported by a small grant from defibrotide’s manufacturer, Jazz Pharma, although they had no role in the study design or data interpretation. Defibrotide is a very interesting FDA-approved drug that we (and others) have considered to be a potential treatment for catastrophic APS (CAPS) and even severe cases of COVID-19. In this paper, we found that defibrotide acts as “super sponge” to soak up toxic proteins called histones in the bloodstream. Histones are released when cells die and normally exist at only low levels in blood. But, in certain disease states such as CAPS and COVID-19, they are present at very high levels where they essentially set the blood vessels on fire. This leads to organ damage and blood clotting. There is still work to do, but the data presented in the paper suggest that defibrotide may be a perfect extinguisher for this histone fire! Read the abstract here.