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Mediastinal lymphadenopathy, class-switched auto-antibodies and myocardial immune-complexes during heart failure in rodents and humans

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Title: Mediastinal lymphadenopathy, class-switched auto-antibodies and myocardial immune-complexes during heart failure in rodents and humans
Authors: Sintou, A
Mansfield, C
Iacob, A-O
Chowdhury, RA
Narodden, S
Rothery, SM
Podoveo, R
Sanchez Alonso, JL
Ferraro, E
Swiatlowska, P
Harding, S
Prasad, S
Rosenthal, N
Gorelik, J
Sattler, S
Item Type: Journal Article
Abstract: Mediastinal lymphadenopathy and auto-antibodies are clinical phenomena during ischemic heart failure pointing to an autoimmune response against the heart. T and B cell have been convincingly demonstrated to be activated after myocardial infarction, a prerequisite for the generation of mature auto-antibodies. Yet, little is known about the immunoglobulin isotype repertoire thus pathological potential of anti-heart auto-antibodies during heart failure. We obtained human myocardial tissue from ischemic heart failure patients and induced experimental MI in rats. We found that anti-heart autoimmunity persists during heart failure. Rat mediastinal lymph nodes are enlarged and contain active secondary follicles with mature isotype-switched IgG2a B cells. Mature IgG2a auto-antibodies specific for cardiac antigens are present in rat heart failure serum, and IgG and complement C3 deposits are evident in heart failure tissue of both rats and human patients. Previously established myocardial inflammation, and the herein provided proof of B cell maturation in lymph nodes and myocardial deposition of mature auto-antibodies, provide all the hallmark signs of an established autoimmune response in chronic heart failure.
Issue Date: 7-Aug-2020
Date of Acceptance: 8-Jul-2020
URI: http://hdl.handle.net/10044/1/81380
DOI: 10.3389/fcell.2020.00695
ISSN: 2296-634X
Publisher: Frontiers Media
Start Page: 1
End Page: 12
Journal / Book Title: Frontiers in Cell and Developmental Biology
Volume: 8
Copyright Statement: © 2020 Sintou, Mansfield, Iacob, Chowdhury, Narodden, Rothery, Podovei, Sanchez-Alonso, Ferraro, Swiatlowska, Harding, Prasad, Rosenthal, Gorelik and Sattler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Funder's Grant Number: RM/13/1/30157
PG/16/93/32345
RM/17/1/33377
RG/17/13/33173
Publication Status: Published
Article Number: 695
Online Publication Date: 2020-08-07
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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