Adriana H. Tremoulet (United States of America)

University of California San Diego Pediatrics
Dr. Adriana Tremoulet is a Professor of Clinical Pediatrics in the Division of Host-Microbe Systems and Therapeutics in the Department of Pediatrics at UC San Diego, specializing in pediatric infectious diseases, Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Chidlren (MIS-C), and pediatric clinical pharmacology. She has served as the Associate Director of the KD Research Center at UC San Diego since 2007, where her research focuses on repurposing therapeutics in Phase I through III clinical trials, including infliximab, atorvastatin and anakinra for KD patients. She has a passion for pediatric pharmacology and serves as the co-principal investigator of the NIH-funded UC San Diego Research Program in Developmental Pharmacology, co-Director of the UC San Diego Department of Pediatric Clinical Pharmacology T32 Training Program and co-director of the Altman Clinical Trials Research Institute KL2 program. As a native Spanish speaker, she has established the KD Latin American Network, which engages more than 300 investigators from 20 Latin American countries in collecting prospective data from KD and MIS-C patients. She has served as a member of the Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the AHA Young Hearts Council since 2015 and now serves as the Chair of this committee. She is passionate about training the next generation of diverse physician-scientists.

Author Of 3 Presentations

From Bench to Bedside: The Treatment of MISC/PIMS

Date
Wed, 11.05.2022
Session Time
13:40 - 15:10
Session Type
Joint Symposium
Room
BANQUETING HALL
Lecture Time
14:12 - 14:42

THE IDENTIFICATION AND SUBSEQUENT CROSS-PLATFORM VALIDATION OF A HOST GENE EXPRESSION SIGNATURE FOR DIFFERENTIATING BETWEEN MIS-C AND OTHER INFECTIOUS AND INFLAMMATORY DISEASES

Date
Wed, 11.05.2022
Session Time
13:40 - 15:10
Session Type
Joint Symposium
Room
BANQUETING HALL
Lecture Time
14:58 - 15:06

Abstract

Backgrounds:

Multisystem Inflammatory Syndrome in Children (MIS-C) occurs several weeks after SARS-CoV-2 infection with symptoms including fever, shock and multiorgan failure. Clinical features of MIS-C overlap with Kawasaki Disease (KD), bacterial, and viral infections, making accurate diagnosis challenging. Host genes, measurable through whole blood transcriptomics, are an alternative tool for diagnosing infectious and inflammatory diseases.

Methods

Patients with MIS-C, KD, bacterial, and viral infections were recruited to the EU-funded PERFORM and DIAMONDS studies and the NIH-funded PREVAIL study. Patients were phenotyped using a standardised algorithm. Genome wide RNA sequencing of whole blood was undertaken, and feature selection was performed to identify a diagnostic signature for distinguishing between MIS-C and other infectious and inflammatory conditions. The expression levels of the genes identified were measured using RT-qPCR assays in an independent validation cohort.

Results:

Through feature selection and differential expression analysis, 11 genes with diagnostic potential were identified and taken forward into cross-platform validation using RT-qPCR. With up to 11 genes, it was possible to distinguish between MIS-C vs. KD, bacterial, and viral infections with high accuracy, with an AUC of 92.9% (95% CI: 88.2%-97.6%) in the validation cohort. The diagnostic gene signature retained its high performance when tested within the groups separately in the validation cohort: MIS-C vs. bacterial infections (AUC: 94.6%), vs. viral infections (AUC: 93.1%), and vs. KD (AUC: 89.8%).

Conclusions/Learning Points:

Despite the clinical similarities between MIS-C and other infectious and inflammatory conditions, there are key differences in gene expression profiles that can be used in diagnostic contexts. It will be necessary for the genes reported here to undergo further validation prior to their development into tests with clinical utility.

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NO EVIDENCE OF AUTO-ANTIBODY BINDING TO CARDIAC TISSUE IN MIS-C AND COVID-19 VACCINATION INDUCED CARDIOMYOPATHY

Date
Wed, 11.05.2022
Session Time
10:00 - 11:02
Session Type
Oral Presentations Session
Room
BANQUETING HALL
Lecture Time
10:32 - 10:42

Abstract

Backgrounds:

Cardiomyopathy is one of the significant features of SARS-CoV-2 induced multi-system inflammatory syndrome in children (MIS-C) and it is also a rare complication of mRNA COVID-19 vaccination in young adults. MIS-C occurs 4-6 weeks following SARS-CoV-2 infection; we therefore postulated that antibodies might play a role in the cardiac immunopathology. The mechanism of vaccine-induced myocarditis is currently being explored. We investigated the role of anti-cardiac antibodies in post SARS-CoV-2 vaccine myocarditis and MIS-C.

Methods:

Clinical cohort: Pre-treatment acute MIS-C (n=10), acute COVID-19 vaccination-induced myocarditis (n=10), Pre-COVID-19 pandemic healthy children (n=10) and healthy COVID-19 vaccinated adults (10).

Immunohistochemistry was performed on human left ventricular tissue sections from 2 donor hearts (deemed unsuitable for donation) for assessment of auto-antibody binding. Sera from patients and controls were used as primary antibodies. FITC-conjugated anti-human-IgG (1:150), IgM (1:150) and IgA (1:50) were used for detection. 10 images were taken at random from each section and immunoglobulin deposition was quantified by calculating mean fluorescent intensity using ImageJ/Fiji. This method has previously shown specific binding of IgG to cardiac tissue following treatment with serum obtained from an adult myocarditis patient.

Results:

No specific binding was seen in left ventricular tissue treated with sera from paediatric patients with either MIS-C or COVID-19 vaccine-induced myocarditis. There was no significant difference in the mean fluorescent intensity of IgG, IgM and IgA in patients compared to controls (Figure 1).

figure1.png

Conclusions/Learning Points:

Our study did not find evidence for a role of an anti-cardiac antibody-mediated inflammatory process in MIS-C cardiomyopathy and COVID-19 vaccine induced myocarditis.

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Presenter Of 1 Presentation

From Bench to Bedside: The Treatment of MISC/PIMS

Date
Wed, 11.05.2022
Session Time
13:40 - 15:10
Session Type
Joint Symposium
Room
BANQUETING HALL
Lecture Time
14:12 - 14:42