Lehnhardt A, Mengel M, Pape L, Ehrich J H H, Offner G, Strehlau J
Department of Pediatric Nephrology, Hepatology and Metabolic Diseases, Hannover Medical School, D-30623 Hannover, Germany.
Am J Transplant. 2006 Apr;6(4):847-51. doi: 10.1111/j.1600-6143.2006.01246.x.
Acute rejection episodes leading to treatment refractory early graft loss are increasingly rare events in living related renal transplantation today. Pathophysiologic pathways often remain unsolved. We report on tubulointerstitial and vascular rejection developing within 2 weeks after transplantation in a 12-year-old boy treated with cyclosporine, mycophenolate, steroids and double blinded basiliximab. Despite steroid pulses, switch to tacrolimus and ATG serum creatinine peaked at 347 micromol/L with imminent graft loss and ongoing C4d negative cellular vascular rejection. Permanent gain of function was only achieved after a single dose of rituximab. Retrospectively CD20+ nodular B-cell aggregates could be demonstrated in all three biopsies obtained prior to rituximab and resolved concomitantly with functional improvement. Our case for the first time demonstrates resolution of nodular CD20+ infiltrates and decline of OX40, NF-kappaB and CTL transcription shortly after rituximab indicating a B-cell facilitated C4d negative pathway. Single dose rituximab may effectively reverse even long-lasting refractory rejection.
在当今亲属活体肾移植中，导致治疗难治性早期移植物丢失的急性排斥反应越来越罕见。病理生理途径往往仍未明确。我们报告了一名12岁男孩在接受环孢素、霉酚酸酯、类固醇和双盲巴利昔单抗治疗后，移植后2周内发生肾小管间质和血管排斥反应的情况。尽管使用了类固醇冲击治疗，改用他克莫司和抗胸腺细胞球蛋白，但血清肌酐仍升至347微摩尔/升，移植物即将丢失，且持续存在C4d阴性细胞性血管排斥反应。仅在单次使用利妥昔单抗后，肾功能才得以永久性恢复。回顾性分析显示，在使用利妥昔单抗之前获取的所有三次活检中均可见CD20+结节状B细胞聚集，且随着功能改善而消退。我们的病例首次证明，利妥昔单抗治疗后不久，结节状CD20+浸润消退，OX40、核因子κB和细胞毒性T淋巴细胞转录水平下降，提示存在一条由B细胞介导的C4d阴性途径。单次使用利妥昔单抗甚至可能有效逆转长期难治性排斥反应。
