House Dust Mite Specific Antibodies induce Neutrophilic Inflammation in the Heart.

ABSTRACT

Rationale Inflammatory heart disorders are among the causes of human death. The causative factors of heart inflammation are to be further elucidated. House dust mite (HDM)-derived protein antigens are involved in the pathogenesis of many human diseases. This study aims to investigate the role of HDM-specific autoantibodies in the pathogenesis of heart inflammation. Methods: Human heart tissue samples were obtained from surgically removed hearts in heart transplantation. The interaction of the heart tissues with HDM-specific antibodies was assessed by pertinent immune analysis. The role of HDM-specific autoantibodies in the induction of heart inflammation was assessed with a murine model. Results: HDM-specific IgG (mIgG) was detected in the serum of patients with myocarditis (Mcd); the mIgG titers were positively correlated with the neutrophil counts in the heart tissues. The mIgG specifically bound to keratin-10 (KRT10) in heart vascular endothelial cells and the heart tissue protein extracts. The amounts of C3a, C5a and C5b-9 were increased in the mouse heart tissues after exposing to mIgG. In the presence of the complement-containing serum, mIgG bound cardiovascular epithelial monolayers to impair the barrier functions. Administration of mIgG or HDM induced the Mcd-like inflammation in the heart, in which neutrophils were the dominant cellular components in the infiltration of inflammatory cells. Conclusions: Mcd patients with neutrophilic inflammation in the heart had higher serum levels of mIgG. The mIgG bound heart endothelial cells to impair the endothelial barrier functions and induce neutrophilic inflammation in the heart.