Naturally acquired anti-αGal antibodies in a murine allograft model similar to delayed xenograft rejection

: Antibodies directed against galactose-α1,3-galactose (αGal) are believed to play an important a role in the pathogenesis of delayed xenograft rejection (DXR). This study was designed to determine whether α1,3-galactosyltransferase-deficient (Gal KO) mice can naturally acquire a sufficient anti-αGal titre to cause the delayed type rejection of αGal-expressing hearts. Gal KO mice of various ages were assessed for anti-αGal antibody levels. αGal-expressing hearts were transplanted heterotopically into these mice and monitored daily. Rejecting and surviving hearts were evaluated histologically. Results: in Gal KO mice greater than 6-month-old, 64% had an anti-αGal antibody titre above the background level. When wild-type αGal-expressing hearts were transplanted into this group, 45% of grafts rejected within 5 to 13 days. Histological examination of the rejected hearts displayed marked tissue damage and an inflammatory infiltrate of predominantly macrophage/monocytes. Surviving grafts showed preserved morphology. Like humans, Gal KO mice naturally develop anti-αGal antibodies with age. The titre in these mice was sufficient to cause a “delayed-type” rejection of a significant proportion of αGal-expressing cardiac grafts. This model thus provides an opportunity to investigate the role of naturally acquired anti-αGal antibodies in the pathogenesis of DXR.