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.


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.


CONCLUSIONS
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.
Mangold
A
A
Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria.
Szerafin
T
T
Hoetzenecker
K
K
Hacker
S
S
Lichtenauer
M
M
Niederpold
T
T
Nickl
S
S
Dworschak
M
M
Blumer
R
R
Auer
J
J
Ankersmit
H J
HJ
D000368:Aged; D000818:Animals; D000918:Antibody Specificity; D001705:Bioprosthesis; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000601:surgery*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology*; D007150:Immunohistochemistry; D008875:Middle Aged; D011184:Postoperative Period; D013552:Swine; D013997:Time Factors; D000519:alpha-Galactosidase / Q000276:immunology*
D000939:Epitopes; D007074:Immunoglobulin G; D000519:alpha-Galactosidase