Hashemi Sara, Hod-Dvorai Reut, Tong Rebecca, Suo Liye
Division of Nephrology and Transplantation The State University of New York Upstate Medical University (SUNY Upstate Medical University), Syracuse, New York 13210, USA.
Department of Pathology The State University of New York Upstate Medical University (SUNY Upstate Medical University), Syracuse, New York 13210, USA.
Case Rep Transplant. 2024 Sep 6;2024:9226321. doi: 10.1155/2024/9226321. eCollection 2024.
Plasma cell-rich acute rejection (PCAR), a relatively rare subtype of acute allograft rejection, is usually associated with a significantly lower treatment response rate and a higher graft failure rate. PCAR is characterized by the presence of more than 10% of plasma cells out of all graft infiltrating cells, with approximately 40%-60% of PCAR resulting in graft failure within a year. Currently, there is no gold standard for the effective treatment of PCAR. This case report demonstrates the potential treatment effect of bortezomib in PCAR. A 37-year-old woman with reflux nephropathy received a kidney transplant from a brain-dead kidney donor. The patient presented with an acute kidney injury with a serum creatinine level over 4 mg/dL 4 months after the surgery. The allograft biopsy showed acute T cell-mediated rejection (TCMR), Grade IIA, plasma cell-rich variant. There were diffuse polyclonal plasma cells infiltrating the renal parenchyma with marked tubulitis and focal endarteritis. She received a methylprednisolone pulse of 500 mg daily x3, followed by thymoglobulin (rATG) at 4.2 mg/kg. However, a repeated biopsy after 2 months showed persistent plasma cells infiltrate with increased interstitial fibrosis with tubular atrophy. Then, the patient was given one cycle of bortezomib with a total of four subcutaneous injections and continued immunosuppressants of tacrolimus, mycophenolate mofetil, and prednisone. Following the treatment, the patient's serum creatinine level trended down to 2 mg/dL, and a second repeat biopsy after 4 months showed a significant treatment effect with complete resolution of interstitial inflammation and decreased chronicity. Bortezomib is a proteasome inhibitor that prevents cell proliferation by inducing apoptosis in plasma cells and has shown great promise as a therapeutic agent for multiple myeloma. Our case suggests that bortezomib can also be used as a potential therapeutic intervention for patients with PCAR.
富含浆细胞的急性排斥反应（PCAR）是急性同种异体移植排斥反应中一种相对罕见的亚型，通常与显著较低的治疗反应率和较高的移植失败率相关。PCAR的特征是在所有移植浸润细胞中浆细胞占比超过10%，约40%-60%的PCAR会在一年内导致移植失败。目前，对于PCAR的有效治疗尚无金标准。本病例报告展示了硼替佐米对PCAR的潜在治疗效果。一名37岁反流性肾病女性接受了来自脑死亡供肾者的肾移植。术后4个月，患者出现急性肾损伤，血清肌酐水平超过4mg/dL。移植肾活检显示为急性T细胞介导的排斥反应（TCMR），IIA级，富含浆细胞变异型。有弥漫性多克隆浆细胞浸润肾实质，伴有明显的肾小管炎和局灶性动脉内膜炎。她接受了每日500mg×3的甲泼尼龙冲击治疗，随后给予4.2mg/kg的抗胸腺细胞球蛋白（rATG）。然而，2个月后重复活检显示浆细胞持续浸润，间质纤维化增加伴肾小管萎缩。然后，患者接受了一个疗程的硼替佐米治疗，共进行了4次皮下注射，并继续使用他克莫司、霉酚酸酯和泼尼松等免疫抑制剂。治疗后，患者的血清肌酐水平降至2mg/dL，4个月后第二次重复活检显示有显著治疗效果，间质炎症完全消退，慢性化程度降低。硼替佐米是一种蛋白酶体抑制剂，通过诱导浆细胞凋亡来阻止细胞增殖，已显示出作为多发性骨髓瘤治疗药物的巨大潜力。我们的病例表明，硼替佐米也可作为PCAR患者的一种潜在治疗干预措施。
