Gavin Poppei
Research Mentor(s): Yu Zuo
Mentor Department: Internal Medicine
Authors: Gavin Poppei, Katarina Kmetova, Kavya Sugur, Srilakshmi Yalavarthi, Julia Ford, Ora Gewurz-Singer, Yu (Ray) Zuo
Session: Session 7 (4:00pm – 4: 50pm)
Presentation Type: Poster 15
Abstract
Aortitis is an inflammatory vasculopathy that can lead to life-threatening complications. Clinically Isolated Aortitis (CIA), refers to aortitis detected via imaging or surgical pathology without clinical evidence of systemic autoimmune disease or involvement of other vascular territories. The absence of clear clinical symptoms makes CIA particularly challenging to diagnose, underscoring the need for reliable biomarkers to enable early detection and intervention. The pathogenesis of CIA remains poorly understood, complicating risk stratification and treatment strategies. While neutrophils play a well-established role in large-vessel vasculitides such as giant cell arteritis (GCA) and Takayasu arteritis (TAK), their contribution to CIA remains unknown. This project aims to determine whether neutrophil activation markers, particularly those associated with neutrophil extracellular traps (NETs), could serve as mechanistically informed biomarkers for CIA. We measured plasma levels of NET-associated and neutrophil activation markers including calprotectin, myeloperoxidase-DNA complexes, and citrullinated histone H3 in 27 CIA patients, alongside cohorts of 11 GCA, 7 TAK, and 6 thoracic aortic aneurysm (TAA) patients, and 25 controls, recruited from University of Michigan. Our preliminary findings show higher plasma calprotectin levels in CIA patients compared to controls (p<0.001), with a strong positive correlation with C-reactive protein (r=0.454, p<0.05). Notably, among the markers studied, calprotectin was the only one uniquely elevated in CIA. Building on these findings, we aim to elucidate the mechanistic role of calprotectin in CIA pathogenesis, particularly its effects on endothelial cells and vascular smooth muscle cells. Given its association with neutrophil activation and NET formation, we propose that calprotectin could serve as a biomarker to aid in risk stratification and early intervention for CIA patients.
