蛋白A免疫吸附对致敏的肾移植等待患者疗效差异分析
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摘要
目的探讨蛋白A免疫吸附治疗对群体反应抗体(PRA)致敏的肾移植等待患者的治疗效果,并分析疗效差异的原因。方法 2015年12月至2018年6月收治的PRA致敏的等待接受肾移植的维持性血液透析患者11例,进行蛋白A免疫吸附治疗31例次,测定每次治疗前后PRA、抗人白细胞抗原(HLA)抗体、免疫球蛋白、血常规、肝功能、凝血等指标,观察不良反应情况。结果 11例患者31例次治疗均未出现不良反应,与治疗前相比,10例患者PRA水平显著下降[(8.152±1.759)%vs(16.850±2.369)%,P<0.01]。在进行蛋白A免疫吸附治疗2～3次后,PRA均转为阴性至2.5%;其PRA分型9例为HLA-Ⅰ类抗体表型,1例为抗HLA-Ⅰ+Ⅱ类抗体混合表型,该10例中1例成功进行同种异体肾移植术;另1例连续治疗2次,PRA在治疗前、后无变化,其PRA分型为抗HLA-DR53抗体,属抗HLA-Ⅱ类抗体。31例次免疫吸附治疗后免疫球蛋白(Ig)G明显下降(P<0.01),IgM、IgA无明显变化(P均>0.05)。与治疗前比较,治疗后HGB、PLT、FIB、PT、TBIL、ALT、ALB均无显著变化(P均>0.05),仅APTT较治疗前增高(P<0.01)。治疗结束后,PRA明显下降的10例患者,1个月后复查PRA指标再次升高,也包括已经接受肾移植术的1例,该例经严密观察临床症状及体征,目前临床随访2.5年,未发生排斥反应。结论蛋白A免疫吸附能够降低维持性血液透析肾移植等待患者的血清PRA水平,其疗效可能与PRA抗体分型有关。
Objective To investigate the therapeutic effect of protein A-based immunoadsorption in patients sensitized by panel reaction antibody(PRA)waiting for renal allografts,and analyze the reasons of the difference of efficacy.Methods From December 2015 to June 2018,11 PRA-sensitized maintenance hemodialysis patients awaiting for renal transplantation received 31 times of protein A immunosorbent therapy.PRA,anti human leukocyte antigen(HLA) antibody,immunoglobulin(Ig),blood routine,liver function and coagulation index before and after each treatment were detected.The adverse reactions were observed.Results No adverse reactions occurred in the treatment of 31 times for 11 cases.Compared with pre-treatment,the PRA level significantly decreased [(8.152±1.759)% vs(16.850±2.369)%,P<0.01] and turned negative to 2.5% after 2～3 times of protein A-based immunoadsorption therapy in 10 cases in whom 9 cases had the phenotype of anti HLA-I antibody for PRA typing,and 1 case had the mixed phenotype of anti HLA-(Ⅰ+Ⅱ) antibody.One of the 10 cases was successfully performed renal allotransplantation.Another case was continuously treated for 2 times,while the PRA level unchanged compared with pre-treatment who had anti specific phenotype of anti HLA-DR53 antibody belonged to anti HLA-Ⅱ antibody for PRA typing.After 31 times of protein A-based immunoadsorption therapy,IgG declined obviously(P<0.01),while IgM and IgA unchanged(all P>0.05).Compared with before treatment,there were no significant changes in HGB,PLT,FIB,PT,TBIL,ALT and ALB after treatment(all P>0.05),but only APTT increased after treatment(P<0.01).After end of treatment,the PRA level increased again when re-checking at 1 month after treatment in 10 patients including 1 case of allograft kidney transplantation who had no rejection after clinical follow-up of 2.5 years by close observation of clinical symptoms and signs.Conclusion Protein A-based immunoadsorption can reduce serum PRA levels of patients waiting for renal allografts in performing maintenance hemodialysis,and its efficacy may be related to typing of PRA antibody.
Objective To investigate the therapeutic effect of protein A-based immunoadsorption in patients sensitized by panel reaction antibody(PRA)waiting for renal allografts,and analyze the reasons of the difference of efficacy.Methods From December 2015 to June 2018,11 PRA-sensitized maintenance hemodialysis patients awaiting for renal transplantation received 31 times of protein A immunosorbent therapy.PRA,anti human leukocyte antigen(HLA) antibody,immunoglobulin(Ig),blood routine,liver function and coagulation index before and after each treatment were detected.The adverse reactions were observed.Results No adverse reactions occurred in the treatment of 31 times for 11 cases.Compared with pre-treatment,the PRA level significantly decreased [(8.152±1.759)% vs(16.850±2.369)%,P<0.01] and turned negative to 2.5% after 2～3 times of protein A-based immunoadsorption therapy in 10 cases in whom 9 cases had the phenotype of anti HLA-I antibody for PRA typing,and 1 case had the mixed phenotype of anti HLA-(Ⅰ+Ⅱ) antibody.One of the 10 cases was successfully performed renal allotransplantation.Another case was continuously treated for 2 times,while the PRA level unchanged compared with pre-treatment who had anti specific phenotype of anti HLA-DR53 antibody belonged to anti HLA-Ⅱ antibody for PRA typing.After 31 times of protein A-based immunoadsorption therapy,IgG declined obviously(P<0.01),while IgM and IgA unchanged(all P>0.05).Compared with before treatment,there were no significant changes in HGB,PLT,FIB,PT,TBIL,ALT and ALB after treatment(all P>0.05),but only APTT increased after treatment(P<0.01).After end of treatment,the PRA level increased again when re-checking at 1 month after treatment in 10 patients including 1 case of allograft kidney transplantation who had no rejection after clinical follow-up of 2.5 years by close observation of clinical symptoms and signs.Conclusion Protein A-based immunoadsorption can reduce serum PRA levels of patients waiting for renal allografts in performing maintenance hemodialysis,and its efficacy may be related to typing of PRA antibody.
引文
[1] 林华,陈怀周,欧明林,等.蛋白A免疫吸附治疗人类白细胞抗原抗体阳性肾移植受者的效果[J].国际移植与血液净化杂志,2017,15(5):12-16.
[2] Schwartz J,Padmanabhan A,Aqui N,et al.Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis:The Seventh Special Issue[J].J Clin Apher,2016,31(3):149-162.
[3] 林华,陈结晶,陈怀周,等.Luminex技术监测抗HLA抗体对肾移植受者预后的影响[J].器官移植,2016,7(5):386-389,393.
[4] Cai J,Terasaki PI.Current trend of induction and maintenance treatment in positive panel-reactive antibody patients:a report on OPTN/UNOS kidney transplant registry data[J].Chin Med J,2011,124(5):649-654.
[5] 陈国栋,史磊,邱江,等.术前群体反应性抗体水平对肾移植接受率和术后长期疗效的影响[J].实用器官移植电子杂志,2013,1(4):235-239.
[6] Gloor J,Stegall MD.Sensitized renal transplant recipients:current protocols and future directions[J].Nat Rev Nephrol,2010,6(5):297-306.
[7] Liu JF,Wang WX,Xue J,et al.Comparing the autoantibody levels and clinical efficacy of double filtration plasmapheresis,immunoadsorption,and intravenous immunoglobulin for the treatment of late-onset myasthenia gravis[J].Ther Apher Dial,2010,14(2):153-160.
[8] Zhang YY,Tang Z,Chen DM,et al.Comparison of double filtration plasmapheresis with immunoadsorption therapy in patients with anti-glomerular basement membrane nephritis[J].BMC Nephrol,2014,15:128.
[9] Winters JL.Apheresis in the treatment of idiopathic dilated cardiomyopathy[J].J Clin Apher,2012,27(6):312-319.
[10] Maillard N,Absi L,Claisse G,et al.Protein A-Based Immunoadsorption Is More Efficient Than Conventional Plasma Exchange to Remove Circulating Anti-HLA Antibodies[J].Blood Purif,2015,40(2):167-172.
[11] 杜云英,张旭峰,陈校园,等.重组蛋白A免疫吸附剂的制备及吸附性能[J].北京化工大学学报(自然版),2011,38(3):92-96.
[12] Cecka JM,Kucheryavaya AY,Reinsmoen NL,et al.Calculated PRA:initial results show benefits for sensitized patients and a reduction in positive crossmatches[J].Am J Transplant,2011,11(4):719-724.
[13] Matignon M,Leibler C,Moranne O,et al.Anti-HLA sensitization after kidney allograft nephrectomy:changes one year post-surgery and beneficial effect of intravenous immunoglobulin[J].Clin Transplant,2016,30(6):731-740.
[2] Schwartz J,Padmanabhan A,Aqui N,et al.Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis:The Seventh Special Issue[J].J Clin Apher,2016,31(3):149-162.
[3] 林华,陈结晶,陈怀周,等.Luminex技术监测抗HLA抗体对肾移植受者预后的影响[J].器官移植,2016,7(5):386-389,393.
[4] Cai J,Terasaki PI.Current trend of induction and maintenance treatment in positive panel-reactive antibody patients:a report on OPTN/UNOS kidney transplant registry data[J].Chin Med J,2011,124(5):649-654.
[5] 陈国栋,史磊,邱江,等.术前群体反应性抗体水平对肾移植接受率和术后长期疗效的影响[J].实用器官移植电子杂志,2013,1(4):235-239.
[6] Gloor J,Stegall MD.Sensitized renal transplant recipients:current protocols and future directions[J].Nat Rev Nephrol,2010,6(5):297-306.
[7] Liu JF,Wang WX,Xue J,et al.Comparing the autoantibody levels and clinical efficacy of double filtration plasmapheresis,immunoadsorption,and intravenous immunoglobulin for the treatment of late-onset myasthenia gravis[J].Ther Apher Dial,2010,14(2):153-160.
[8] Zhang YY,Tang Z,Chen DM,et al.Comparison of double filtration plasmapheresis with immunoadsorption therapy in patients with anti-glomerular basement membrane nephritis[J].BMC Nephrol,2014,15:128.
[9] Winters JL.Apheresis in the treatment of idiopathic dilated cardiomyopathy[J].J Clin Apher,2012,27(6):312-319.
[10] Maillard N,Absi L,Claisse G,et al.Protein A-Based Immunoadsorption Is More Efficient Than Conventional Plasma Exchange to Remove Circulating Anti-HLA Antibodies[J].Blood Purif,2015,40(2):167-172.
[11] 杜云英,张旭峰,陈校园,等.重组蛋白A免疫吸附剂的制备及吸附性能[J].北京化工大学学报(自然版),2011,38(3):92-96.
[12] Cecka JM,Kucheryavaya AY,Reinsmoen NL,et al.Calculated PRA:initial results show benefits for sensitized patients and a reduction in positive crossmatches[J].Am J Transplant,2011,11(4):719-724.
[13] Matignon M,Leibler C,Moranne O,et al.Anti-HLA sensitization after kidney allograft nephrectomy:changes one year post-surgery and beneficial effect of intravenous immunoglobulin[J].Clin Transplant,2016,30(6):731-740.