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Prevalence and Correlates of Anti-DSG2 Antibodies in Arrhythmogenic Right Ventricular Cardiomyopathy and Myocarditis: Immunological Insights from a Multicenter Study

Journal of Clinical Medicine, ISSN: 2077-0383, Vol: 13, Issue: 22
2024
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  • Citations
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  • Mentions
    1
    • News Mentions
      1
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Study Findings from University of Padova Advance Knowledge in Arrhythmogenic Right Ventricular Dysplasia (Prevalence and Correlates of Anti-DSG2 Antibodies in Arrhythmogenic Right Ventricular Cardiomyopathy and Myocarditis: Immunological ...)

2024 NOV 26 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Cardiovascular Daily -- Investigators discuss new findings in arrhythmogenic right ventricular dysplasia.

Article Description

Background: Autoantibodies against Desmoglein-2 desmosomal protein (anti-DSG2-ab) were identified in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) by Enzyme-Linked ImmunoSorbent Assay (ELISA); anti-intercalated disk autoantibodies (AIDAs) were identified in myocarditis and (ARVC) by indirect immunofluorescence (IFL). We aim to assess: (1) anti-DSG2-ab specificity in ARVC and myocarditis, (2) accuracy of anti-DSG2-ab detection by ELISA versus AIDA by IFL, and (3) clinical correlates of anti-DSG2-ab in ARVC. Methods: We included 77 patients with ARVC, 91 with myocarditis/dilated cardiomyopathy (DCM), 27 with systemic immune-mediated diseases, and 50 controls. Anti-heart antibodies (AHAs) and AIDAs were assessed by IFL, and anti-DSG2-ab by ELISA (assessed both by optical density, OD, and U/L). Receiving operator curve (ROC) analysis was used to assess ELISA diagnostic accuracy. Results: A relevant proportion (56%) of ARVC patients was anti-DSG2-ab-positive, with higher anti-DSG2-ab levels than controls. Anti-DSG2-ab titer was not different between ARVC and myocarditis/DCM patients (48% anti-DSG-ab positive). Frequency of anti-DSG2 positivity by ELISA was higher in AIDA-positive cases by IFL than AIDA-negative cases (p = 0.039 for OD, p = 0.023 for U/L). In ARVC, AIDA-positive patients were more likely to be AHA-positive (p < 0.001), had pre-syncope (p = 0.025), and abnormalities in cardiac rhythm (p = 0.03) than ARVC AIDA-negative patients, while anti-DSG2-ab positivity did not have clinical correlates. Conclusions: Anti-DG2-ab detection in ARVC and myocarditis/DCM reflects immune-mediated pathogenesis to desmosomal proteins. Higher frequency of anti-DSG2-ab positivity by ELISA by U/L was higher in AIDA-positive cases by IFL than AIDA-negative cases, in keeping with the hypothesis that DSG2 is one of AIDA autoantigens. In ARVC, AIDA status but not anti-DSG2-ab showed distinct clinical correlates, possibly reflecting a wider AIDA autoantigenic spectrum.

Bibliographic Details

Giordani, Andrea Silvio; Pontara, Elena; Vicenzetto, Cristina; Baritussio, Anna; Peloso Cattini, Maria Grazia; Bison, Elisa; Re, Federica; Marcolongo, Renzo; Joseph, Shaylyn; Chatterjee, Diptendu; Fatah, Meena; Hamilton, Robert M; Caforio, Alida Linda Patrizia

MDPI AG

Medicine

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