Commentary: From Old World monkeys to New World humans-Evolved protection from tick bites and bioprosthetic material.

In a fascinating twist of evolution, Old World monkeys, apes, and humans developed a remarkable inactivation of the alpha-1,3-galactosyltransferase gene, which, in turn resulted in a unique recognition of alpha-gal epitope so that high titers of antibodies against this antigen are produced. Although in nature this evolutionary advantage protected us against tick bites and other arthropod vector-borne diseases, in clinical practice, it may cause a spectrum of immune response from immediate anaphylaxis to xenotransplantation to delayed calcifications of bioprosthetic material. This phenomenon, including delayed anaphylaxis to red meat consumption, is known as alpha-gal syndrome.,

Next-generation bioprosthetic valves for transcatheter and surgical implantation should have optimal tissue biocompatibility to minimize inflammatory immune response.

Drs Antonia Schulz, Igor E. Konstantinov, and Edward Buratto

See Article page 85.

In the last decade, an increasing variety of patients have benefitted from transcatheter aortic valve implantation (TAVI) as an alternative to surgical aortic valve replacement., In this issue of the Journal, Veraar and colleagues challenge us to improve the biocompatibility of bioprosthetic heart valves used for TAVI, as it might be a limiting factor for durability. The study demonstrates significantly increased serum concentrations of alpha-gal–specific antibodies, augmented complement activity, and nonspecific inflammation in 27 patients 3 months after TAVI compared with patients undergoing a MitraClip procedure, who served as controls. Similar xenograft-specific immune response has been observed after surgical bioprosthetic valve replacement., Alpha-gal epitopes were also identified in decellularized bioprosthetic material when complete decellularization was not achieved. The resulting humoral response leads to activation of the complement system, triggering endothelial cell dysfunction, platelet aggregation, and promotes calcification.,9, 10, 11

Although the presented study of Veraar and colleagues did not explore any relationship between the degree of immunogenic response and valve durability, other groups were able to show an association of anti–alpha-gal antibodies and premature bioprosthetic valve degeneration. Furthermore, several experimental studies demonstrated a connection between anti–alpha-gal antibodies and the calcification process in valvular bioprosthesis., Less immunogenic materials and improved processing methods have already been described to increase biocompatibility and to prevent an immunologic response to the xenogenic valve tissue., It appears that a proper understanding of alpha-gal syndrome is important to improve the longevity of bioprosthetic material13, 14, 15, 16, 17 in patients with a wide range of congenital and acquired heart disease.