Michigan Medicine APS Program Update

ANTIPHOSPHOLIPID SYNDROME (APS) PROGRAM UPDATE

Thank you for your interest in and support of our APS Program! We continue to pursue personalized, proactive treatments for APS with a long-term goal of a cure. We do this work to make lives better, and we hope we can use these emails to build a community of others who want the same. We’re all in this together!

NEWS & ACHIEVEMENTS

Labiotech Beyond Biotech Podcast: Antiphospholipid Syndrome

Dr. Jason Knight discusses current and potential future treatments for APS, research being conducted by the APS Research Labs and others, training the next generation of researchers, and the importance of increasing awareness of the disease. Listen to the podcast.

Lupus Research Program Presents Impact Award Recipients

The Congressionally Directed Medical Research Programs presents the FY2021 Lupus Research Program Impact Award recipients, including the APS Research Lab's project “Endothelial Cells and the Origins of Antiphospholipid Vasculopathy". Read more.

Associate Division Chief for Research – Dr. Jason Knight

Congratulations to Dr. Jason Knight who was recently named Associate Division Chief for Research. Learn more about Dr. Knight and what he hopes to achieve in this role and as the Director of the Rheumatology T32 Training Program.

RESEARCH & CLINICAL TRIALS

APS Research Labs Discover a New Aspect of APS

Congratulations to Katarína Kmeťová who led a new study published by our APS Research Labs in the journal Clinical Immunology. As you may recall, Katarína trained in Slovakia before joining our labs as a visiting scholar and, now, a full-time researcher. The study also involved collaboration with researchers at McGill University in Quebec, Canada and the University of Illinois Chicago.

In the study, Katarína and the team found evidence to support one of our longstanding hypotheses - namely, that a key protein/antigen in APS called beta-2 glycoprotein I (β₂GPI) not only interacts with the phospholipids that line cell membranes, but also neutrophil extracellular traps (NETs).

NETs are sticky microscopic spiderwebs built of DNA and proteins that are released into the blood when white blood cells are under too much stress. The released NETs then amplify inflammation and blood clotting. We therefore think they are bad for APS.

The strong negative charge of DNA (which is also a feature of many phospholipids) likely explains the interaction between positively-charged β₂GPI and NETs. Opposites attract!

While more work lies ahead, our working theory is that β₂GPI is attempting to “detoxify” the NETs, but this process is unsuccessful - and may actually make the NETs more toxic - in the presence of the anti-β₂GPI antibodies that are found in the blood of many patients with APS.

You can read the full paper here: Interaction of the Antiphospholipid Syndrome Autoantigen Beta-2 Glycoprotein I with DNA and Neutrophil Extracellular Traps. If you are unable to access it, email Dr. Knight and he will send you a copy.

APS Pregnancy Experience – Community-Engaged Research

Led by Dr. Alex Harper, the APS Pregnancy Experience study is seeking to understand the experiences, priorities, and concerns surrounding pregnancy for individuals diagnosed with APS.

We have so far recruited approximately two-thirds of the desired 100 participants. If you meet the entry criteria, please consider participating! This is your chance to help shape our research agenda for the coming years! Learn more and participate in the study.

In Case You Missed It! - DARE-APS

Since 2019, Dr. Knight and the APS Research Labs have been working with Dr. Doruk Erkan and his team at the Hospital for Special Surgery, APS ACTION, and researchers at both the National Institutes of Health and the Immune Tolerance Network to develop a first-of-its-kind clinical trial for individuals living with APS.

DARE-APS Study: We all know that new safe and effective treatments for APS are needed. In this research study, we will learn about the safety of the drug Darzalex® (daratumumab) in patients with APS and will also learn whether it reduces levels of the antiphospholipid antibodies that cause APS.

About the Study Drug: Daratumumab is an antibody that targets a protein called CD38, which is found on the surface of the immune cells that produce antiphospholipid antibodies (plasma cells). In APS, daratumumab may work by eliminating these antiphospholipid antibody-producing cells, thereby reducing damage to the body caused by antiphospholipid antibodies.

Daratumumab is currently approved by the U.S. Food and Drug Administration (FDA) to treat a blood cancer called multiple myeloma. However, it has not been tested in patients with APS and is therefore considered an experimental treatment in the DARE-APS study.

Participating in DARE-APS: Participation in DARE-APS will occur in two phases. During the treatment phase, participants will receive 8 weekly intravenous (IV) doses of daratumumab. The post-treatment follow-up phase will last an additional 10 months, during which 6 monitoring clinical visits will occur.

Eligibility: You may be eligible to participate in DARE-APS if you:

Are between ages 18 and 65
Have a diagnosis of APS
Do not have lupus
Have had certain problems associated with APS in the past 5 years such as blood clots or pregnancy complications

Learn More: To learn more, visit the DARE-APS website.

Our site (University of Michigan in Ann Arbor, MI), the Hospital for Special Surgery located in New York, NY, and Northwell Health in Great Neck, NY are actively recruiting for this study!

APS 101: AUGUST 2023

Lupus Anticoagulant Lab Test

APS 101, written by Dr. Jacqueline Madison, was created to provide facts and information about APS to help everyone better understand the ins and outs of APS. In this month’s edition, Dr. Madison discusses the oddly named “lupus anticoagulant” lab test - the history behind the name, and the questions the test answers. Read more.

SPARK BARK:

WHAT’S SPARKY UP TO A-HOUND TOWN?

by Amelia K. Knight

Howdy everyone! As you may recall, Sparky is a 7-year-old beagle. My family and I adopted him after a good Samaritan found him frolicking down some old country roads. Sparky is known for getting into buffoonery, and these past two months definitely did not disappoint.

In early July, Sparky's beagle friend Dexter stayed with us for a week while his people were out of town. While you may think that having two beagles would be a whimsical experience, that’s not necessarily true. It was double trouble. At first, Sparky was really excited to see Dexter. They ran around the backyard and Sparky showed him the ropes. Dexter was even shown the correct way to guard the yard from deer and other woodland creatures. This caused a lot of arrooing to say the least.

Eventually, Dexter became kind of a ringleader and Sparky followed along, suspecting that if a guest was involved, the risk of serious scolding would surely be less. It was hard to know where those beagle buddies might be prowling in the house while hoping for a sniff, a scratch, or ideally a next meal.

Outside, they did learn to station themselves in opposite corners of the backyard making it almost impossible to corral them both inside. Beagles are not necessarily the most graceful or well-behaved dogs, so they were always causing a ruckus. I think at the end of the week Sparky was getting jealous that another beagle was getting attention including some of his scratches, so when Dexter left he seemed to be glad to be king of the castle again.

(L to R): Sparky and Dexter

While that is already a lot of beagliness for two months, there was more. In late July, my family and I went on vacation to the West Coast (of Michigan) and decided to bring King Sparky. Of course, when we were packing all of our things, Sparky was kind of in shambles because he thought we were going to leave him behind. So, he did his best to imitate a piece of luggage and was very relieved when he was able to hop into the car.

After three long hours, we made it. When Sparky got inside the cabin that we rented, he went sniffing in every corner. He was so excited. He then did a bunch of back-rolls on the furniture (don’t tell). Soon, he discovered there was a fenced-in backyard! That is where he spent most of his time, basking and sniffing. Although Sparky didn’t enjoy the backyard as much as the one at home, it seemed there were a lot of new scents for him. He was really living it up as a beach dog.

That’s all for now! Thanks for coming to my Spark Bark!

SUPPORT OUR WORK

Donations to our lab are used to support new pilot projects that are difficult to fund from other sources. Every bit helps. And we are always open to your ideas!

To make a gift to support our APS research, please visit the APS Gift Fund.