Enhanced immunoglobulin expression after prolonged mechanical support with left ventricular assist devices in myocardial samples from patients with severe congestive heart failure: a possible indicator of augmented humoral responsiveness

Abstract

Prolonged mechanical support with left ventricular assist devices (LVADs) has become commonplace as a bridge to cardiac transplantation in patients with severe congestive heart failure (CHF). Patients with LVAD support have immune sensitization characterized by increased levels of panel reactive antibodies (PRAs). Prior work by others implicates B cell activation in patients with LVADs. LVAD support also decreases the expression of proteins whose expression is abnormally enhanced by CHF. To evaluate the effect of LVAD support on immunoglobulin (Ig) expression, we examined left ventricular (LV) tissue obtained from 8 patients at the time of LVAD implantation and subsequently at the time of cardiectomy and LVAD removal for cardiac transplantation after prolonged LVAD support. The abundance of mRNA for genes of interest was determined in matched LV tissues from these 8 patients by performing a broad analysis of gene expression using an Affymetrix chip platform examining 60,000 defined gene sequences. The mRNA was compared between LV samples from LVAD implantation and from cardiectomy. 54 genes were noted to have significant up-regulation at cardiectomy compared to LVAD implantation. In particular, the genes for the Ig heavy constant γ and μ regions and Igκ and λ regions showed significantly enhanced LV expression at cardiectomy compared to LV from LVAD insertion, indicating enhanced expression in the LV as a result of LVAD support. This enhanced expression ranged from a 3.6 fold increase for Igκ constant region to a 16.02 fold increase in the Ig heavy constant gamma 3(G3m) gene. In contrast, natiuretic peptide (NP) expression declined 5.88 fold from LVAD insertion to cardiectomy. This latter finding is consistent with previous observations from our group and others that LVAD support results in decreased NP expression. We conclude that LVAD support results in enhanced expression of Ig genes, most likely reflecting activation of immune cells in the LV which subsequently produce these Ig and may play a role in the elevated PRAs after LVAD support.