Fig. 1: Key players in the pathogenesis of lupus myocarditis.
From: Pathogenic drivers of lupus myocarditis and potential therapeutic targets
The activation of antibodies (Abs) and T cells targeting nuclear antigens such as double-stranded DNA (dsDNA), Sjögren’s syndrome A (SSA), Sjögren’s syndrome B (SSB), ribonucleoprotein (RNP) and Smith (Sm) is initiated by apoptotic cells, contributing to the development of lupus myocarditis. In addition, cardiac antigen-specific autoantibodies and autoreactive T cells, targeting cardiac MyHC, cardiac troponin I (cTnI) and β1-adrenergic receptor (β1AR), play a pathogenic role by damaging cardiomyocytes. MyHC-specific T cells can further differentiate into tissue-resident memory T (TRM cells in the heart. Some anti-nuclear antigen antibodies may recognize cardiomyocytes as an antigen through cross-reactivity to calcium (Ca) channels. The development of autoreactive T cells is associated with the expression of susceptible human leukocyte antigen (HLA) alleles and the presentation of neoself-antigens due to loss or decrease of invariant chain (Ii) expression. Furthermore, antiphospholipid antibodies bind directly to cardiolipin and β2 glycoprotein I (β2GPI) on endothelial cells and platelets, driving cardiovascular inflammation.
