蛋白A免疫吸附联合利妥昔单抗在PRA阳性肾移植受者中的应用七例报告

目的 探讨术前群体反应性抗体(PRA)阳性的肾移植受者应用蛋白A免疫吸附联合利妥昔单抗(RTX)治疗的效果及安全性.方法 7例中,行二次肾移植者5例,有多次妊娠史者2例.7例均行亲属活体供肾移植,供者均为男性.供、受者ABO血型相同,补体依赖细胞毒试验阴性,HLA抗原错配数2～5个.术前单纯PRAⅠ类抗体增高者2例,单纯PRAⅡ类抗体增高者2例,PRA Ⅰ、Ⅱ类抗体均增高者3例;IgG平均为13.4 g/L,IgA平均为1.78 g/L,IgM平均为1.47 g/L.术前行免疫吸附2～10次,平均为5次.当患者PRA或免疫球蛋白水平降至正常值及以下时进行移植,并于手术当天单次静脉输注RTX 600 mg,同时给予抗淋巴细胞球蛋白或抗胸腺细胞球蛋白.术后采用他克莫司(或环孢素A)、霉酚酸酯及泼尼松预防排斥反应.监测患者血肌酐及内生肌酐清除率(Ccr);临床上考虑患者发生排斥反应时,行移植肾穿刺活检;分别于术前及术后1周测定患者外周血中CD19+和CD20+细胞百分比(仅检测3例).结果 免疫吸附及RTX治疗期间,患者均未出现不良反应.行免疫吸附后,7例患者的PRA Ⅰ、Ⅱ类抗体均有所下降,IgG、IgA和IgM的平均值也有所下降.术后患者移植肾功能恢复良好,未发生移植肾功能恢复延迟,其中3例分别在术后8、10和14 d出现急性排斥反应,治疗后均逆转.术前患者外周血中CD19+细胞分别为1.98%、4.64%和4.45%,CD20+细胞分别为15.15%、2.01%和1.15%;术后1周时,其外周血中CD19+细胞分别为0.39%、0.98%和0.11%,CD20+细胞分别为0.34%、0.15%和0.01%.术后1例发生肺部巨细胞病毒感染,治疗后好转,1例因肺部烟曲霉感染而死亡,死亡时肾功能正常.结论 对于术前PRA阳性者应用蛋白A免疫吸附及RTX治疗有一定效果,经处理后患者可接受肾移植.

Protein A immunoadsorption combined with rituximab in renal transplant recipients positive for panel reactive antibody(Report of 7 cases)

Objective To investigate the safety and efficacy of combined use of protein A immunoadsorption and rituximab(RTX)in kidney transplant recipients positive for panel reactive antibody(PRA).Methods Five cases received second transplantation,and 2 cases had the history of multiple pregnancies.All the cases received living-related kidney transplantation and all grafts came from male donors.Recipients and donors had the same blood type,and complement dependent cytotoxic (CDC)was negative.HLA mismatch number was 2-5.Three out of 7 cases had high PRA of both class Ⅰ and 11,2 cases had high class Ⅰ,and the rest 2 had high class Ⅱ.Mean immunoglobulin IgG,IgA,and IgM levels were 13.4,1.78,and 1.47g/L respectively.All patients were pretreated with immunoabsorption for 2-10 times(mean 5 times).Immunoglobulin and PRA changes were monitored before and after absorption.Transplantation was done after PRA or immunoglobulin levels were reduced to normal or below normal values.Before the transplantations single dose of RTX(375 mg/m2)was infused together with polyclonal antibody induction.All patients received immunosuppressive agents such as tacrolimus or cyclosporin A,mycophenolate mofetil and prednisone after transplantation.Creatinine(Cr),and creatinine clearance rate(Ccr)were monitored after transplantatioa Biopsy would be performed when rejection occurred.The percentage of peripheral blood B lymphocytes CD19 and CD20 was determined in 3 patients by using flow cytometry before transplantation and one week posttransplantation.Results There was no adverse reactions during the combined use of protein A immunoadsorption and RTX.The PRA of class Ⅰ and Ⅱ was descended after administration of protein A immunoadsorption.The average levels of IgG,IgA and IgM were also descended.Seven cases of kidney transplantation had a good recovery,with no delayed graft function (DGF).Three cases had acute rejection 8,10 and 14 days after transplantation respectively.Successful reversion was achieved after treatment.CD 19 before transplantation was 1.98 %,4.64 % and 4.45 % respectively,and 0.39 %,0.98 % and 0.11 % respectively after transplantation;CD 20 before transplantation was 15.15 %,2.01 % and 1.15% respectively,and 0.34 %,0.15 % and 0.01 % respectively after transplantatioa One patient developed a cytomegalovirus infection in lung,and successful reversion was achieved after treatment.One patient died of Aspergillus pneumonia with normal graft function.Conclusion The combined use of protein A immunoadsorption and RTX were effective to decrease the risk of the patients positive for PRA.After treatment,the patients could receive a successful kidney transplantation.