Lattimore Sherene, Skill Nicholas J, Maluccio Mary A, Elliott Holly, Dobben Elizabeth, Shafuddin Asif, Goggins William C
Division of Transplant, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.
Transplant Direct. 2019 Sep 27;5(10):e493. doi: 10.1097/TXD.0000000000000933. eCollection 2019 Oct.
Rabbit antithymocyte globulin (rATG) use for immunosuppression induction is widespread but is contraindicated by the presence of anti-rATG antibodies. This study reports the incidence of positive anti-rATG antibody titers in patients before and after renal transplant and evaluates associated outcomes and costs. In addition, it will correlate CD40L and interleukin (IL)-21 with anti-rATG antibody titers.
Clinical and billing records from the Indiana University Transplant Laboratory were reviewed for positive versus negative anti-rATG antibody titers, graft survival, and 7-day readmission costs between 2004 and 2018. Serum from patients with positive and negative rATG antibody titers were quantitated for CD40L and IL-21 by enzyme-linked immunosorbent assay.
On average, between 2004 and May 2018, 163 kidney transplants per year were performed. Anti-rATG antibody titers were ordered for 17 patients/year, of which 18.2% were positive at 1:100 titer either pre- or post-transplant. Time to graft loss correlated with a positive rATG titer at time of readmission. Moreover, second kidney transplant increased the anti-rATG positive rate. A weak correlation was observed between anti-rATG titer and recipient age. Seven-day readmission treatment costs were significantly lower in patients with positive anti-rATG titer. IL-21 and CD40L were significantly greater in patients with positive anti-rATG titers after transplant when compared with negative anti rATG patients.
Positive anti-rATG antibody titer is associated with a significant negative impact on outcomes. Monitoring of anti-rATG antibody titer is recommended to optimize treatment options in patients, especially in the setting of second transplants. Elucidation of the mechanisms associated with positive anti-rATG antibody is required. IL-21 and CD40L are potential targets for future study.
兔抗胸腺细胞球蛋白(rATG)用于免疫抑制诱导很普遍,但存在抗rATG抗体时则为禁忌。本研究报告了肾移植患者移植前后抗rATG抗体滴度呈阳性的发生率,并评估了相关结局和费用。此外,还将研究CD40L和白细胞介素(IL)-21与抗rATG抗体滴度之间的相关性。
回顾了印第安纳大学移植实验室2004年至2018年间抗rATG抗体滴度呈阳性与阴性的临床及计费记录、移植物存活情况以及7天再入院费用。通过酶联免疫吸附测定法定量检测抗rATG抗体滴度呈阳性和阴性患者血清中的CD40L和IL-21。
2004年至2018年5月期间,平均每年进行163例肾移植手术。每年对17例患者检测抗rATG抗体滴度,其中18.2%在移植前或移植后抗体滴度为1:100时呈阳性。再入院时移植物丢失时间与rATG滴度呈阳性相关。此外,再次进行肾移植会增加抗rATG阳性率。抗rATG滴度与受者年龄之间存在弱相关性。抗rATG抗体滴度呈阳性的患者7天再入院治疗费用显著更低。与抗rATG抗体滴度呈阴性的患者相比,移植后抗rATG抗体滴度呈阳性的患者体内IL-21和CD40L显著更高。
抗rATG抗体滴度呈阳性对结局有显著负面影响。建议监测抗rATG抗体滴度,以优化患者的治疗方案,尤其是在再次移植的情况下。需要阐明与抗rATG抗体呈阳性相关的机制。IL-21和CD40L是未来研究的潜在靶点。