The role of xenoreactive natural antibody in pig-to-human lung xenotransplantation
Introduction The lung, as a donor graft, has high antigenecity and infectivity, due to some immunological and anatomical special features. Therefore long-term morbidity and mortality after lung allotransplantation would probably be higher than that of other organ grafts. Similarly, lungs from human decay accelerating factor (h-DAF) transgenic pig are rejected easily compared to h-DAF modified heart, kidney, and liver in xenotransplantation. In addition ABO blood groups have been said to be involved in xenotransplantation, because anti-B antibody crossreacts with the αGal antigen. The purpose of this study is to clarify the role of xenoreactive natural antibodies (XNA) in re-modelling hyperacute rejection (HAR) and delayed xenograft rejection (DXR), and the participation of ABO blood groups in pig-to-human lung xenotransplantation.
Materials and methods (1) For re-modelling of HAR, the binding capacity of XNA to pulmonary microvascular endothelial cells was quantified with human serum by ELISA. (2) The relationship between XNA and ABO blood groups was evaluated. Anti-B antibody titer was determined by mixed cell agglutination reaction and the possibility of ABO blood groups as a recipient selection factor was evaluated. (3) Re-modelling of DXR by cytotoxicic assay was performed.
Results (1) The binding capacity of XNA IgG was equivalent to that of IgM, and the same results were obtained with immunocytochemical staining. (2) the binding capacity of XNA in blood groups A and O were significantly higher than B and AB. A significant positive correlation was observed between the binding capacity of XNA and anti-B antibody. (3) DXR was mainly induced bt XNA IgG, not IgM.
Conclusion The role of XNA IgG and IgM are similar in HSAR, but IgG in DXR, and anti-B antibody can be a recipient selection factor in lung xenotransplantation.