Abstract 13769: AT1R Autoantibody Levels Are Elevated in Patients Who Required Immunosuppression Escalation in Immune Checkpoint Inhibitor Mediated Myocarditis

Abstract

Intro: Angiotensin-II (Ang-II) plays an important role in the pathophysiology of various cardiovascular disorders, including cardiomyopathy and hypertension. Angiotensin II type 1 receptor (AT1R) mediates the deleterious effects of Ang-II and can cause vasoconstriction, vascular and cardiac remodeling, and cell death. Animal models have shown that the AT1R signal is obligatory for the development of virus-induced myocardial injury through the proinflammatory action of Ang-II. Data from animal studies and human case studies showed AT1R autoantibodies (AT1R A) were a novel mediator of vasomotor changes and LV dysfunction related to acute myocarditis and that blocking AT1R can be effective. Hypothesis: Little is known whether patients on immune checkpoint inhibitors (ICI) develop AT1R A and whether this can worsen the severity of ICI myocarditis. We measured AT1R A in 9 hospitalized patients who were diagnosed with ICI induced myocarditis. We describe this cohort, the course of their illness and their response to steroids. Methods: This was a prospective study. Quantitative antibodies to AT1R at the time of hospitalization were measured by an Enzyme Linked Immunosorbent Assay (ELISA) (One Lambda) and classified as positive (>17U/mL); at risk (10-17 U/mL) and negative (<10 U/mL). Results: Demographic and co-morbidity details are shown (Table 1). 5/9 patients (55%) were either positive or at risk for AT1R A elevation. 4/9 patients (45%) were AT1R A negative. 4/5 (80%) of the AT1R A positive/at risk required increased immunosuppression whereas 1/4 (25%) of the AT1R A negative required increased immunosuppression for myocarditis. Conclusions: AT1R autoantibodies may worsen the severity of ICI myocarditis. A larger cohort study and comparisons of AT1R A levels in non-ICI patients are underway. If trends hold true, testing for AT1R A and treating with an angiotensin receptor blocker may be a potential strategy to reduce ICI myocarditis severity.