Abstract Presenters: Nader Yatim, MD, PhD, Postdoctoral Fellow, Icahn School of Medicine at Mount Sinai, and Brian Y. Soong, Student, Icahn School of Medicine at Mount Sinai
Abstract Title: Clonal Hematopoiesis Orchestrates Giant Cell Arteritis Disease Trajectory and Immune Landscape: A Multicentric and Multiomics Approach
Abstract Session: Plenary II (1820-1825), 10–11:30 a.m., Monday, November 9
What is your abstract about?
Dr. Yatim: Our study investigates how clonal hematopoiesis (CH), an age-related expansion of blood-cell clones carrying acquired mutations, affects giant cell arteritis (GCA). Across four cohorts comprising 260 patients, clonal hematopoiesis was present in approximately half of patients and independently predicted relapse, with larger clones associated with greater risk. By integrating single-cell sequencing of blood with serum proteomics and spatial transcriptomics of temporal artery biopsies, we found that myeloid cells from patients harboring CH mutations acquire tissue-dependent inflammatory phenotypes within affected arteries. In particular, DNMT3A mutations were associated with an SPP1+MMP12+ macrophage state linked to matrix degradation, intimal fibrosis, and vascular remodeling.
Why did you decide to investigate this topic?
Dr. Yatim: Many age-related inflammatory diseases have been epidemiologically linked to CH, but the mechanisms underlying these associations remain poorly understood. This observation was the starting point for our work. We set out to establish an integrated translational pipeline spanning the clinical characterization of the CH-associated GCA spectrum and deep immune profiling of the affected arterial wall. Our goal is to understand how somatic mutations in blood cells contribute to vascular inflammation and disease heterogeneity, and ultimately to identify new therapeutic targets for GCA.
What are you working on next related to this research?
Dr. Yatim: We are working to validate these findings in larger cohorts and define the mechanisms through which CH-mutant myeloid cells acquire pathogenic phenotypes after entering the arterial wall. We aim to identify the cellular interactions that establish and sustain the SPP1+MMP12+ macrophage niche. Ultimately, we hope to uncover new therapeutic targets for GCA and potentially other age-related inflammatory diseases associated with clonal hematopoiesis.
What excites you most about your work?
Dr. Yatim: What excites me most is the ability to connect an acquired genetic alteration in the blood with cellular behavior inside an inflamed human artery, and ultimately with a patient’s clinical course. By studying the disease across the circulation, serum, and tissue, we can begin to understand how the local environment shapes mutant immune cells. This may help us move toward a more biologically informed understanding of GCA heterogeneity and, eventually, more individualized patient care.
What are you most looking forward to at ACR Convergence 2026 in Orlando?
Dr. Yatim: I am most looking forward to sharing these findings and discussing them with clinicians, scientists, and patients who approach GCA from different perspectives. ACR Convergence provides an exceptional opportunity to receive constructive feedback, build new collaborations, and learn about advances that could shape the next phase of this work. I am particularly excited to exchange ideas about aging, clonal hematopoiesis, vascular inflammation, and how emerging molecular insights can be translated into better care for patients with GCA.
THERE’S STILL TIME TO JOIN US
If you haven’t registered for ACR Convergence 2026, you can still register on-site at the Orange County Convention Center in Orlando, Florida, through November 11. All registered participants receive on-demand access to scientific sessions through September 30, 2027.
