Autonomic PASC Syndromes Arising from Functional Autoantibodies against G-protein Coupled Receptors
Date Published March 10, 2026
Project Date July 2024 - June 2026
Understanding the mechanisms behind autonomic PASC syndromes caused by functional autoantibodies targeting GPCRs.
| “Autonomic PASC Syndromes Arising from Functional Autoantibodies against G-protein Coupled Receptors,” addresses a pressing and emerging dimension of post-acute sequelae of SARS-CoV-2 infection (PASC) by investigating how functional autoantibodies directed at G-protein coupled receptors (GPCRs) may drive autonomic dysfunction. The work, funded through a National Institutes of Health subaward to ATSU-KCOM, aims to understand mechanisms linking autoimmune responses to the diverse autonomic manifestations observed in patients following acute COVID-19. Autonomic PASC can present with symptoms such as orthostatic intolerance, tachycardia, blood pressure instability, gastrointestinal dysmotility, and other dysautonomia features that substantially impair quality of life. By focusing on autoantibodies that alter GPCR function—receptors integral to cardiovascular, gastrointestinal, and autonomic regulatory pathways—this research seeks to connect molecular immune changes to clinical syndromes. The proposed work comprises experimental and translational components designed to identify, characterize, and test the functional effects of GPCR-targeting autoantibodies derived from individuals with autonomic PASC. Elmslie’s team will use immunological assays to detect and quantify autoantibody specificities, functional in vitro systems to measure receptor signaling modulation, and possibly ex vivo or cellular models to observe downstream physiological effects. Through these approaches, the project will determine whether autoantibodies act as agonists, antagonists, or allosteric modulators of key GPCRs, and how such interactions perturb autonomic homeostasis. This mechanistic focus aims to clarify causative links rather than mere associations, providing evidence that could stratify patients by pathophysiology and identify biomarkers predictive of autonomic PASC trajectories. Beyond mechanistic discovery, the research has translational implications: defining pathogenic autoantibodies could support diagnostic testing to confirm autoimmune-mediated autonomic disorders in post-COVID patients, inform prognosis, and guide targeted therapeutic strategies such as immunomodulation, plasmapheresis, or receptor-specific interventions. By pinpointing specific GPCR targets, the study also opens avenues for repurposing or developing agents that normalize receptor function. The funding period from July 2024 to June 2026 will allow Elmslie to generate foundational data needed for larger-scale studies and clinical translation. Overall, this project situates immunology, receptor pharmacology, and autonomic neuroscience at the intersection of a significant public health challenge. Elmslie’s investigation into functional autoantibodies against GPCRs seeks to transform understanding of autonomic PASC from descriptive clinical observation to mechanistic insight, enabling more precise diagnostics and tailored therapies for patients experiencing persistent, debilitating autonomic symptoms after COVID-19. |
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COM Affiliations
- A.T. Still University of Health Sciences - Kirksville College of Osteopathic Medicine
- A.T. Still University-School of Osteopathic Medicine in Arizona
Funding Amount
$167,792
Funding Type
Federal Government Award
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