RESUMO
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.
RESUMO
<p><b>BACKGROUND</b>The status of sensitization in kidney transplant recipients in the last 10 years and the trend of induction and maintenance therapy in patients of different panel-reactive antibody (PRA) levels have not been analyzed. The aim of this study was to investigate the current status of pre-transplant sensitization and its association with graft outcome.</p><p><b>METHODS</b>A total of 155 570 kidney transplants reported to United Network for Organ Sharing (UNOS) during 2000 - 2009 were included in this study. We investigated the current status of pre-transplant sensitization and its association with graft outcome, and also compared the usage trend of 16 induction agents and 7 maintenance immunosuppressants in patients at different PRA levels. The difference of distributions of categorical variables between groups was investigated using the chi-square test. Unpaired t test or one-way analysis of variance (ANOVA) were used for numerical variables. The survival rates of transplant recipients were estimated using Kaplan-Meier methods and significance was determined by Log-rank test. Two-side P value < 0.05 was considered statistically significant. All statistical analyses were performed using STATA 10 with all available updates as of March 2010 (StataCorp LP, College Station, Texas 77845, USA).</p><p><b>RESULTS</b>Despite the fact of the decreased percentages of kidney transplant recipients with presensitization history, the mean PRA levels of all kidney recipients has been increasing in the last 7 years, which was possibly due to the introduction of more sensitive antibody testing techniques. The percentage of patients with treated rejection episodes within one year post-transplant were significantly higher in sensitized patients (PRA = 50% - 100%:14.3% and PRA = 1% - 49%:13.9%) than in non-sensitized patients (12.4%). Both 1- and 5-year graft survival rates improved in the last 10 years; this was more significant in high PRA patients. Thymoglobulin was the most commonly used induction agent in last 10 years. Its users increased from 10% to 46% in non-sensitized patients, from 12% to 57% in PRA 1% - 49% patients, and from 19% to 63% in PRA 50% - 100% patients. The users of Campath, intravenous immunoglobulin (IVIG), and Rituximab have been increasing and reached 16%, 20%, and 11% in highly sensitized patients. In the last 5 years, steroid-free patients were 33% - 36%, 30% - 37%, and 10% - 25% for PRA 0, 1% - 49%, and 50% - 100% respectively. Almost 90% of patients were on Prograf at discharge. It seems that Myfortic users have been increasing since 2005 and it may soon replace mycophenolate mofetil (MMF) if long-term follow-up study conforms its safety and efficacy.</p><p><b>CONCLUSIONS</b>Application of sensitive antibody testing techniques increased the mean PRA levels of transplant recipients in spite of a decreased percentage of sensitized recipients. Induction and maintenance therapy differed in patients at different PRA levels.</p>