Interactions between the recipient immune system and the left ventricular assist device surface: Immunological and clinical implications

Silviu Itescu, Ranjit John

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

The unquestionable clinical success of left ventricular assist device (LVAD) implantation has, nevertheless, been accompanied by complications arising from interactions between the implanted biomaterial and the host immune system. The aberrant state of monocyte and T-cell activation resulting from these host/device interactions is accompanied by two parallel processes: (1) selective loss of Th1 cytokine producing CD4 T-cells through activation-induced cell death; and (2) unopposed activation of Th2 cytokine producing CD4 T-cells resulting in B-cell hyperreactivity and dysregulated immunoglobulin synthesis through Th2 cytokines and heightened CD40 ligand-CD40 interactions. The net results of these events is that, on the one hand, the LVAD recipient develops progressive defects in cellular immunity and is at increased risk of serious infection, and, on the other hand, is more likely to develop allosensitization, posing a significant risk to successful transplant outcome. Intravenous immunoglobulin therapy is an effective and safe modality for sensitized LVAD recipients awaiting cardiac transplantation, reducing serum anti-human lymphoicyte antigen (HLA) alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of intravenous immunoglobulin would appear to be superior to plasmapheresis. Immunosuppression incorporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized LVAD recipients of cardiac transplantation. When used after transplantation as part of triple immunosuppressive regimens, cyclophosphamide is superior to mycophenolate mofetil in reducing episodes of allograft rejection in these patients. Because these immune dysfunctions appear to be related to the effects of excessive biomaterial-associated T-cell activation, future efforts will need to be directed at either altering the physical properties of the materials interacting with the host circulation or pharmacological intervention aimed more selectively at inhibiting T-cell activation.

Original languageEnglish (US)
Pages (from-to)S58-S65
JournalAnnals of Thoracic Surgery
Volume75
Issue number6 SUPPL.
DOIs
StatePublished - Jun 1 2003

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