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NaV1.5 autoantibodies in Brugada syndrome: pathogenetic implications
Adriana Tarantino1,2, Giuseppe Ciconte1,2,3, Dario Melgari1
1Institute for Molecular and Translational Cardiology (IMTC), IRCCS Policlinico San Donato, Piazza Malan, 2, 20097 San Donato Milanese, Milan, Italy.
European Heart Journal
|July 30, 2024
Summary
Autoimmune anti-NaV1.5 antibodies are prevalent in Brugada syndrome (BrS) patients, aiding diagnosis and revealing an immunopathogenic cause beyond genetics. These antibodies induce BrS-like ECG changes, suggesting new therapeutic targets.
Area of Science:
- Cardiology
- Immunology
- Genetics
Background:
- Brugada syndrome (BrS) patients face risks of life-threatening arrhythmias.
- Diagnosis is difficult due to the often-elusive electrocardiographic (ECG) signature.
- While SCN5A gene mutations are implicated, they are found in only 25% of patients.
Purpose of the Study:
- To investigate the presence and impact of anti-NaV1.5 autoantibodies in BrS patients.
- To explore autoimmunity as a potential pathophysiological mechanism in BrS.
- To assess autoantibodies as diagnostic markers and therapeutic targets.
Main Methods:
- Screened plasma from 50 BrS patients and 50 controls for anti-NaV1.5 autoantibodies using western blot, immunoprecipitation, and immunofluorescence.
- Assessed autoantibody impact on sodium current density in cellular models.
- Injected BrS plasma into wild-type mice to evaluate pathophysiological effects.
Main Results:
- Anti-NaV1.5 autoantibodies detected in 90% of BrS patients vs. 6% of controls (AUC=.92, 94% specificity, 90% sensitivity).
- Autoantibodies significantly reduced sodium current density, independent of SCN5A mutation status.
- Mice injected with BrS plasma exhibited Brugada-like ECG abnormalities.
Conclusions:
- The majority of BrS patients possess anti-NaV1.5 autoantibodies, indicating an immunopathogenic component.
- These autoantibodies can serve as diagnostic markers and induce the BrS ECG signature.
- Findings suggest a need for comprehensive diagnostics and open new therapeutic research avenues.
