Abstract
Mediastinal lymphadenopathy and auto-antibodies are clinical phenomena during ischemic heart failure pointing to an autoimmune response against the heart. T and B cells 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.
Highlights
Chronic heart failure (CHF) describes a pathological condition in which the heart is unable to pump enough blood to meet the metabolic demands of the body
Enlargement of the mediastinal lymph nodes draining the heart has been observed during heart failure, but was explained by hemodynamic mechanisms related to cardiac decompensation (Ngom et al, 2001; Pastis et al, 2011)
As described previously (Slanetz et al, 1998; Pastis et al, 2011), mediastinal lymphadenopathy is a common finding in patients with heart failure due to ischemic heart disease (Figure 1A)
Summary
Chronic heart failure (CHF) describes a pathological condition in which the heart is unable to pump enough blood to meet the metabolic demands of the body. A myocardial infarction initiates an adaptive immune response with activation of the heart draining mediastinal lymph nodes, formation of secondary follicles and B cell maturation with production of mature self-reactive auto-antibodies which may subsequently induce cardiomyocyte dysfunction and death. Environment activate and trigger myocardial infiltration of autoreactive B and T cells of the adaptive immune system (VardaBloom et al, 2000; Yan et al, 2013; Zouggari et al, 2013; Tang et al, 2019) These can be long-lived and may cause sustained damage to the myocardium. We detected myocardial deposition of complement, which suggests immunecomplex mediated pathology
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