Long-term desensitization for ABO-incompatible living related kidney transplantation recipients with high refractory and rebound anti-blood type antibody: case report

Abstract Background ABO-incompatible living related kidney transplantation (ABO-iLKT) has increased the possibilities for kidney transplantation in patients with end stage renal disease. Due to advancements in immunosuppressive agents and the identification of immunological conditions following ABO-iLKT, this transplantation technique has achieved the same success rate as ABO-compatible LKT. However, some patients continue to generate anti-blood type antibodies, despite conventional immunosuppressant treatment. Case presentation A 60-year-old man was referred to our hospital for kidney transplantation. The proposed transplant was ABO incompatible, from a donor with blood-type A to a recipient with blood-type O. The recipient’s anti-A blood-type IgG antibody titer was measured at 4096-fold dilution. Following desensitization therapy, including mycophenolate mofetil (MMF) 750 mg/day for 3 months, intravenous Rituximab 200 mg, and two sessions of double filtration plasmapheresis, the anti-A blood-type IgG antibody titer decreased to only 516-fold dilution and did not meet our target of less than 128-fold dilution. MMF was thus continued for an additional 4 months and four additional sessions of plasmapheresis were undertaken. Following these interventions, antibody titers decreased to 128-fold dilution and ABO-iLKT was performed. Following transplant, antibody-mediated rejection was not observed and renal function was preserved. However, a post-operative renal biopsy 1.5 months later showed evidence of T-cell-mediated rejection IB. The patient was treated with steroids, with no increase in serum creatinine. Conclusion Our findings suggest that the long-term single MMF desensitization therapy could be a suitable option for ABO-iLKT with high refractory and rebound anti-blood type antibody. Further studies are required to establish the optimal immunosuppression regimen to control B cell- mediated immunity in ABO-iLKT

Targeted Deletion of Both Thymidine Phosphorylase and Uridine Phosphorylase and Consequent Disorders in Mice

Thymidine phosphorylase (TP) regulates intracellular and plasma thymidine levels. TP deficiency is hypothesized to (i) increase levels of thymidine in plasma, (ii) lead to mitochondrial DNA alterations, and (iii) cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). In order to elucidate the physiological roles of TP, we generated mice deficient in the TP gene. Although TP activity in the liver was inhibited in these mice, it was fully maintained in the small intestine. Murine uridine phosphorylase (UP), unlike human UP, cleaves thymidine, as well as uridine. We therefore generated TP-UP double-knockout (TP(−/−) UP(−/−)) mice. TP activities were inhibited in TP(−/−) UP(−/−) mice, and the level of thymidine in the plasma of TP(−/−) UP(−/−) mice was higher than for TP(−/−) mice. Unexpectedly, we could not observe alterations of mitochondrial DNA or pathological changes in the muscles of the TP(−/−) UP(−/−) mice, even when these mice were fed thymidine for 7 months. However, we did find hyperintense lesions on magnetic resonance T(2) maps in the brain and axonal edema by electron microscopic study of the brain in TP(−/−) UP(−/−) mice. These findings suggested that the inhibition of TP activity caused the elevation of pyrimidine levels in plasma and consequent axonal swelling in the brains of mice. Since lesions in the brain do not appear to be due to mitochondrial alterations and pathological changes in the muscle were not found, this model will provide further insights into the causes of MNGIE