Anti-Ro/SSA Antibodies Blocking Calcium Channels as a Potentially Reversible Cause of Atrioventricular Block in Adults.
L-type calcium channels
anti-Ro/SSA antibodies
autoimmunity
idiopathic atrioventricular block in adults
steroid therapy
Journal
JACC. Clinical electrophysiology
ISSN: 2405-5018
Titre abrégé: JACC Clin Electrophysiol
Pays: United States
ID NLM: 101656995
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
19
01
2023
revised:
10
03
2023
accepted:
10
03
2023
medline:
1
9
2023
pubmed:
25
5
2023
entrez:
25
5
2023
Statut:
ppublish
Résumé
In ∼50% of severe atrioventricular blocks (AVBs) occurring in adults <50 years, the underlying etiology remains unknown. Preliminary evidence from case reports suggests that autoimmunity, specifically the presence of circulating anti-Ro/SSA antibodies in the patient (acquired form), in the patient's mother (late-progressive congenital form), or in both (mixed form), could be involved in a fraction of idiopathic AVBs in adults by possibly targeting the L-type calcium channel (Ca The purpose of this study was to evaluate whether anti-Ro/SSA antibodies are causally implicated in the development of isolated AVBs in adults. Thirty-four consecutive patients with isolated AVB of unknown origin and 17 available mothers were prospectively enrolled in a cross-sectional study. Anti-Ro/SSA antibodies were assessed by fluoroenzyme-immunoassay, immuno-Western blotting, and line-blot immunoassay. Purified immunoglobulin-G (IgG) from anti-Ro/SSA-positive and anti-Ro/SSA-negative subjects were tested on I Anti-Ro/SSA antibodies, particularly anti-Ro/SSA-52kD, were found in 53% of AVB-patients and/or in their mothers, most commonly an acquired or mixed form (two-thirds of cases) without history of autoimmune diseases. Purified IgG from anti-Ro/SSA-positive but not anti-Ro/SSA-negative AVB patients acutely inhibited I Our study points to anti-Ro/SSA antibodies as a novel, epidemiologically relevant and potentially reversible cause of isolated AVB in adults, via an autoimmune-mediated functional interference with the L-type calcium channels. These findings have significant impact on antiarrhythmic therapies by avoiding or delaying pacemaker implantation.
Sections du résumé
BACKGROUND
In ∼50% of severe atrioventricular blocks (AVBs) occurring in adults <50 years, the underlying etiology remains unknown. Preliminary evidence from case reports suggests that autoimmunity, specifically the presence of circulating anti-Ro/SSA antibodies in the patient (acquired form), in the patient's mother (late-progressive congenital form), or in both (mixed form), could be involved in a fraction of idiopathic AVBs in adults by possibly targeting the L-type calcium channel (Ca
OBJECTIVES
The purpose of this study was to evaluate whether anti-Ro/SSA antibodies are causally implicated in the development of isolated AVBs in adults.
METHODS
Thirty-four consecutive patients with isolated AVB of unknown origin and 17 available mothers were prospectively enrolled in a cross-sectional study. Anti-Ro/SSA antibodies were assessed by fluoroenzyme-immunoassay, immuno-Western blotting, and line-blot immunoassay. Purified immunoglobulin-G (IgG) from anti-Ro/SSA-positive and anti-Ro/SSA-negative subjects were tested on I
RESULTS
Anti-Ro/SSA antibodies, particularly anti-Ro/SSA-52kD, were found in 53% of AVB-patients and/or in their mothers, most commonly an acquired or mixed form (two-thirds of cases) without history of autoimmune diseases. Purified IgG from anti-Ro/SSA-positive but not anti-Ro/SSA-negative AVB patients acutely inhibited I
CONCLUSIONS
Our study points to anti-Ro/SSA antibodies as a novel, epidemiologically relevant and potentially reversible cause of isolated AVB in adults, via an autoimmune-mediated functional interference with the L-type calcium channels. These findings have significant impact on antiarrhythmic therapies by avoiding or delaying pacemaker implantation.
Identifiants
pubmed: 37227349
pii: S2405-500X(23)00205-0
doi: 10.1016/j.jacep.2023.03.007
pii:
doi:
Substances chimiques
Calcium Channels
0
Immunoglobulin G
0
Steroids
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1631-1648Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL164415
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures This work was supported by Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), Progetti di Rilevante Interesse Nazionale (PRIN), and Bando 2017, protocollo 2017XZMBYX (to Dr Lazzerini and Dr Capecchi); a Merit Review grant I01 BX002137 from Biomedical Laboratory Research & Development Service of Veterans Affairs Office of Research and Development (to Dr Boutjdir); National Heart, Lung, and Blood Institute grant 1R01HL164415-01 (to Dr Boutjdir); and U.S. Department of Defense award number W81XWH-21-1-0424 (to Dr Boutjdir). Dr Lazzerini has received a grant from Roche Italia S.p.A. outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.