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

Unraveling the Web: Navigating NETs at the Intersection of APS and COVID-19

In December 2023, Dr. Yu (Ray) Zuo presented at the Stanford University Division of Immunology & Rheumatology Seminar where he gave an overview of neutrophils and NETs and discussed the pathogenic role of NETs and anti-NET antibodies in APS and COVID-19. Watch the lecture.

Taxifolin Supplements Demonstrate Protective Effects Against Lupus

A new first-of-its-kind study, led by Dr. Ramadan Ali, found taxifolin supplements have protective effects on thrombo-inflammatory diseases, such as lupus and APS. Read more.

11 Internal Medicine Researchers on Highly Cited Researchers List

Dr. Jason Knight is one of eleven Department of Internal Medicine researchers named to Clarivate's Highly Cited Researchers for 2023. Highly Cited Researchers are selected based on the demonstration of significant and broad influence in their field(s) of research. Read more.

Young Physician-Scientist Awardee

The annual American Society for Clinical Investigation Young Physician-Scientist Award recognizes physician-scientists who are early in their first faculty appointment and have made notable achievements in their research. This year’s nomination pool included 172 nominations with only 52 awards given. We are delighted to announce that Dr. Ray Zuo has been selected for this significant recognition of his research achievements. Read more.

Unveiling Potential Diagnostic, Treatment Target for APS-Related Thrombocytopenia

The APS Research Labs, led by Dr. Ray Zuo, have unveiled a new mechanism that drives thrombocytopenia and a potential clinically actionable biomarker for APS-associated thrombocytopenia. Read More.

APS 101: FEBRUARY 2024

Catastrophic Antiphospholipid Syndrome

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 catastrophic antiphospholipid syndrome, how it affects the body, diagnosis, and treatment. Read more.

RESEARCH & CLINICAL TRIALS

Endothelial Cells and the Origins of Antiphospholipid Blood Vessel Problems

Since September 2022, we have been working on a project generously supported by the Department of Defense’s Lupus Research Program.

As you probably know, livedo reticularis and racemosa are netlike skin discolorations found on the bodies of many patients with APS. The presence of livedo indicates sluggish blood flow in the skin's small blood vessels and sometimes tracks with various “internal” problems of APS, including abnormal brain imaging and even strokes.

For this project, we have been applying cutting-edge methods to the easily accessible blood vessels of the skin. In doing so, we hope to discover what causes APS blood vessels deeper in the body to have problems over time. To date, we have collected skin biopsies from 23 individuals with APS (some with livedo and some without). We greatly appreciate everyone who has participated so far! Each skin specimen was dissociated into a single-cell suspension for RNA analysis.

We still have funding to biopsy five more individuals before we begin the final analysis. We hope that this analysis will identify new therapeutic targets for the problems affecting many of our patients.

If you live near Ann Arbor and would like to provide a sample (small skin biopsy of the upper thigh), please contact Dr. Wenying Liang at [email protected]. Compensation of $50 is provided to each participant.

Learn more about this study and our other clinical trials and research.

New Publications from Our Group

Since we were last in touch, we have published several articles relevant to patients with APS. Look for more detailed stories elsewhere in this newsletter, and in the coming months. In the meantime, here is a brief rundown!

Non-Pharmacological Rehabilitation Interventions for Individuals with Antiphospholipid Syndrome: A Scoping Review (Lupus. 2023. PMID: 38113856)

• Why we did the study: Our patients often ask for approaches beyond medications that can help them feel and function better. We thought we might be missing some clues in the literature.
• Who led the charge: Alex Harper, Yen Chen, Stephanie Tancer, Kyla Rodgers, Amber Crumb
• What we found: While there are hints that approaches beyond anticoagulant medications might help with the neurological, physical, and cognitive symptoms of APS, more research is needed to prove this. A team of specialists, including rehabilitation experts, should test the safety and effectiveness of new interventions, including those involving exercise. Overall, this paper highlights an area of tremendous unmet need that we all must work together to fill!

Calprotectin Impairs Platelet Survival in Patients with Primary Antiphospholipid Syndrome (Arthritis & Rheumatology. 2024. PMID: 38225923)

• Why we did the study: Many of our patients have low platelet counts, but the reason for this isn’t very clear.
• Who led the charge: Claire Hoy, Naveen Kumar, Sherwin Navaz
• What we found: We discovered that the neutrophils of many patients with APS release a factor called calprotectin into the bloodstream. Platelets then eat the calprotectin, which causes them to die. We are now exploring ways to prevent the calprotectin release. We are also looking for ways that calprotectin may be a useful blood test in the clinic as we try to predict which patients are at risk for thrombocytopenia in the future.

Low Ectonucleotidase Activity and Increased Neutrophil-Platelet Aggregates in Patients with Antiphospholipid Syndrome (Blood. 2024. PMID: 38237140)

• Why we did the study: As you can tell, we have recently gotten very interested in platelets! With this study, we were looking for new drug targets that might combat activated platelets and neutrophils in APS.
• Who led the charge: Naveen Kumar, Ajay Tambralli, Bruna Mazetto Fonseca, Sri Yalavarthi
• What we found: We found that the regulation of molecules called purine nucleotides by platelets and neutrophils doesn’t work well in many patients with APS. This leads to these cells clumping together more, which could lead to blood clotting. We think we have discovered at least two different ways we may be able to fix this, and that is what we are working on now.

Longitudinal Plasma Proteomics in CAR-T Cell Therapy Patients Implicates Neutrophils and NETosis in the Genesis of CRS (Blood Advances. 2024. PMID: 38266157)

• Why we did the study: Our colleagues in Oncology asked us to help them with a study of the “cytokine release syndrome” that can happen after CAR-T cell therapy for blood cancers. They thought neutrophils (one of our areas of expertise) might be playing a role.
• Who led the charge (from our team): Kavya Sugur
• What we found: Neutrophils are indeed a big problem in this dangerous condition! In fact, patients whose neutrophils were already somewhat activated before the CAR-T therapy appeared to be at the highest risk. This work will hopefully lead to new, smarter testing and approaches to treatment for cancer patients.

If you need help accessing any of these interesting papers, email us and we will get you a copy.

SPARK BARK:

WHAT’S SPARKY UP TO A-HOUND TOWN?

by Amelia K. Knight

At this point, we all know Sparky, the loveable beagle who wears his heart on his sleeve. As he spins tales of both comedy and tragedy, he has been nicknamed by many “The Modern Shakespeare,” although he doesn’t let that go to his head. Sparky represents a true coming-of-age story since we adopted him after he was found by a good Samaritan perusing the old country roads as a puppy. At 7 years of age, he is (or was until recently) still as agile as in his prime.

Sparky’s humbleness allows him to be pals with other less famous dogs. His buddy, Dexter, came to stay with us for a week over the holidays. Sparky at first was quite excited to meet up with his friend, but the thrill soon faded a bit. Who was this dog stealing the spotlight with the humans? Dexter and Sparky soon became sort of frenemies, at least from Sparky’s perspective. Dexter would happily greet Sparky in the morning, which Sparky would return with an aloof nod. Sparky just felt Dexter was kind of a poser. Acknowledging that these inside shenanigans were a bit awkward, once it was time to play in the backyard, Sparky and Dexter became the best of friends as always. Sparky would show Dexter the ropes of barking up the best trees and guarding the most important corners. Dexter has always been a fast learner, and together the two dogs generated hound barks loud enough to tree a whole family of squirrels.

Unfortunately, heroes are not immune to tragedy. Near the tail end (no pun intended) of Dexter’s stay, Sparky tore his doggy ACL (aka canine cruciate ligament) after running some particularly aggressive circles in celebration of Dexter digging a remarkably large hole in the backyard. We called the vet and they said that something like this can happen to even the most noble of dogs. Everyone was of course in shambles because of this event, with Sparky the most pitiful of all as he could not pursue his true passion of running. Since it was over the holidays, nothing happened very quickly, but we were finally able to schedule a knee surgery for Sparky.

While the surgery seemed to go okay, Sparky hasn’t been allowed to run or jump for over a month. Fortunately, he is at least now out of the cone of shame and back to taking walks on a short leash. Hopefully, he will be able to return to his standard life in the coming months, including getting back to his lightly supervised backyard hijinks!!

That’s all for now! Thanks so much for tuning into this tale of friendship, hardship, and (hopefully) redemption for our protagonist. See you next time!

SUPPORT OUR WORK

Giving Blueday - March 13, 2024

Giving Blueday, taking place this year on March 13, 2024, is a campus-wide giving day for the University of Michigan and Michigan Medicine. From midnight through 11:59 p.m. EST, Michigan Medicine will invite supporters to make donations to areas that they’re passionate about. With social media challenges and real-time updates throughout the day, they’ll encourage donors, friends, faculty, staff, and other supporters to be a Victor and move medicine forward.

Please join us in supporting APS Research by joining us on Wednesday, March 13 to contribute toward our fundraising goal. With your investment in the Division of Rheumatology APS Program, we can accelerate the pace of discovery and change the face of this disease to make life safer, more comfortable, less unpredictable, and ultimately find a cure for thousands of people living with the interruptions and fear of APS. Read more.

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