Anti-Ro/SSA Antibodies Blocking Calcium Channels as a Potentially Reversible Cause of Atrioventricular Block in Adults
Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved..
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 (Cav1.2) and inhibiting the related current (ICaL).
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 ICaL and Cav1.2 expression using tSA201 and HEK293 cells, respectively. Moreover, in 13 AVB patients, the impact of a short course of steroid therapy on AV conduction was evaluated.
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 ICaL and chronically down-regulated Cav1.2 expression. Moreover, anti-Ro/SSA-positive sera showed high reactivity with peptides corresponding to the Cav1.2 channel pore-forming region. Finally, steroid therapy rapidly improved AV conduction in AVB-patients with circulating anti-Ro/SSA antibodies but not in those without.
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.
| Errataetall: |
CommentIn: JACC Clin Electrophysiol. 2023 Aug;9(8 Pt 3):1649-1651. - PMID 37354190 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
JACC. Clinical electrophysiology - 9(2023), 8 Pt 3 vom: 31. Aug., Seite 1631-1648 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lazzerini, Pietro Enea [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.09.2023 Date Revised 07.09.2023 published: Print-Electronic CommentIn: JACC Clin Electrophysiol. 2023 Aug;9(8 Pt 3):1649-1651. - PMID 37354190 Citation Status MEDLINE |
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| doi: |
10.1016/j.jacep.2023.03.007 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357297172 |
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| 245 | 1 | 0 | |a Anti-Ro/SSA Antibodies Blocking Calcium Channels as a Potentially Reversible Cause of Atrioventricular Block in Adults |
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| 500 | |a Date Completed 01.09.2023 | ||
| 500 | |a Date Revised 07.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: JACC Clin Electrophysiol. 2023 Aug;9(8 Pt 3):1649-1651. - PMID 37354190 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 (Cav1.2) and inhibiting the related current (ICaL) | ||
| 520 | |a 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 | ||
| 520 | |a 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 ICaL and Cav1.2 expression using tSA201 and HEK293 cells, respectively. Moreover, in 13 AVB patients, the impact of a short course of steroid therapy on AV conduction was evaluated | ||
| 520 | |a 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 ICaL and chronically down-regulated Cav1.2 expression. Moreover, anti-Ro/SSA-positive sera showed high reactivity with peptides corresponding to the Cav1.2 channel pore-forming region. Finally, steroid therapy rapidly improved AV conduction in AVB-patients with circulating anti-Ro/SSA antibodies but not in those without | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a L-type calcium channels | |
| 650 | 4 | |a anti-Ro/SSA antibodies | |
| 650 | 4 | |a autoimmunity | |
| 650 | 4 | |a idiopathic atrioventricular block in adults | |
| 650 | 4 | |a steroid therapy | |
| 650 | 7 | |a Calcium Channels |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Steroids |2 NLM | |
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