Alpha-Gal specific IgG immune response after implantation of bioprostheses.

BACKGROUND

We have previously shown that the alpha-Gal (Galalpha1.3-Galbeta1-4GlcNAc-R) epitope is a relevant xenoantigen present on bioprostheses utilized in cardiac surgery and elicits an alpha-Gal specific IgM immune response. We sought to investigate whether that immune response continues after valve implantation.

MATERIALS AND METHODS

We collected plasma samples from patients who underwent bioprosthesis implantation (n = 19) or mechanical valve replacement (n = 8), respectively, prior to, at 10 days and at 3 months after cardiac surgery. ELISA was utilized to quantify alpha-Gal specific IgG and IgG subclasses. 3 bioprosthetic tissue samples were obtained from patients who had to undergo re-operation within 1 week (n = 1) or at 12-15 months (n = 2) after the initial operation. We utilized confocal laser scanning microscopy (CLSM) to detect the presence of alpha-Gal epitopes (IB4) and cell nuclei (DAPI).

RESULTS

alpha-Gal specific IgG was significantly increased 3 months after implantation of bioprostheses compared to preoperative values (p < 0.001) and was significantly higher than alpha-Gal specific IgG levels of the control group (p < 0.05). IgG3 was the major subclass directed against alpha-Gal (p < 0.05, pre- vs. postoperative values). In CLSM analysis we demonstrated that bioprostheses explanted 1 week after implantation contained IB4/DAPI positive cells within the collagen matrix. In contrast, in patients who underwent reoperation after 12 months, porcine tissue showed a complete lack of IB4/DAPI.

CONCLUSION

Our results indicate that the implantation of bioprostheses elicits a specific humoral immune response against alpha-Gal bearing cells compared to controls within 3 months after cardiac surgery. The complete absence of IB4/DAPI positive structures 12 months after implantation indicates a specific degradation of alpha-Gal bearing cells through previous exposure to the human blood circuit.