The enlightenment of hemodynamic principleson for prevention and treatment of allograft rejection / 中华器官移植杂志

ABSTRACT

Antibody mediated rejection (AMR) starts from the binding of donor specific antibody (DSA) to its target antigen on endothelium. Whether or not a circulating DSA would bind to its static target depends on the relative strength between the antigen-antibody attraction potential energy and the kinetic energy of a circulating DSA. The attraction potential energy between antigen & antibody mainly depends on affinity of antibody to its target and is relatively constant. The kinetic energy of antibody depends on its velocity. The faster it moves the higher kinetic energy it possesses (E=mV 2/2). Therefore, the primary endothelial injury has always occurred in capillary which has the lowest blood flow rate. Even though DSA moves at the lowest velocity in capillary (≤1 mm/s), compared to its size (diameter<10 nm), the relative velocity of DSA is very high, which moves a distance of 100, 000 diameter of antibody per second. It is nearly 20, 000 times over the highest relative velocity of Bolt, the world record holder in 100 meters. Therefore, it is not easy for a fast-moving DSA to bind to its static target since the attraction potential energy between antigen and antibody needs to overcome the great kinetic energy of DSA. These basic concepts of hemodynamics and the relative velocity of DSA gives us at least the following inspirations: (1)It is easier for a DSA to bind its antigen in vitro, since there is no relative motion between antigen and antibody in test tube; while it is more difficult for a fast-moving DSA to bind to its static antigen in vivo, since the attraction potential energy between antigen & antibody needs to overcome the great kinetic energy of a fast-moving DSA.(2)A cytotoxic agent usually kills its peripheral blood target with a much higher depletion efficacy than for its target in tissue, since it runs with its circulating target without relative motion, while it is more difficult for a fast-moving agent with a great kinetic energy to bind its static target in tissue.(3)Some patients remain positive for DSA for a long time without the evidence of AMR. This is possibly due to a lower attraction potential energy between antigen-antibody, or due to a higher kinetic energy of a fast-moving DSA in the circumstance without microvascular occlusion.(4)Endothelial injury, resulting from ischemia and reperfusion or others, usually cause microvascular thrombosis, which results in partial or complete occlusion of microvascular system and favors antigen-antibody interaction.(5)Based on the fact that blood flow rate can affect antibody-antigen binding, we can reasonably infer that maintaining a good microcirculation in allograft will help to prevent or treat AMR. The strategies may include prevention of leukocyte adhesion, platelet deposition, red blood cell aggregation, and reduction of blood lipid and viscosity, to have plenty of water, and to do regular exercise. These strategies are equally important for prevention or treatment of cell mediated rejection.