Mediastinal lymphadenopathy, class-switched auto-antibodies and myocardial immune-complexes during heart failure in rodents and humans
File(s)fcell-08-00695.pdf (5.22 MB)
Published version
Author(s)
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.
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.
Date Issued
2020-08-07
Date Acceptance
2020-07-08
Citation
Frontiers in Cell and Developmental Biology, 2020, 8, pp.1-12
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/).
License URL
Sponsor
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Identifier
https://www.frontiersin.org/articles/10.3389/fcell.2020.00695/full
Grant Number
RM/13/1/30157
PG/16/93/32345
RM/17/1/33377
RG/17/13/33173
Publication Status
Published
Article Number
695
Date Publish Online
2020-08-07