蛋白A免疫吸附治疗肺移植术后新生DSA介导的急性排斥反应

徐钰; 练巧燕; 陈奥; 王晓华; 徐鑫; 何建行; 巨春蓉

doi:10.3969/j.issn.1674-7445.2022.04.016

蛋白A免疫吸附治疗肺移植术后新生DSA介导的急性排斥反应

doi: 10.3969/j.issn.1674-7445.2022.04.016

510012 广州，广州医科大学附属第一医院广州呼吸健康研究院呼吸疾病国家重点实验室

基金项目:

广东省钟南山医学基金会 ZNSA-2020013

广州呼吸健康研究所基金 2019GIRHZ04

详细信息

作者简介:

通讯作者:
巨春蓉，女，主任医师，教授，博士研究生导师，研究方向为终末期肺病肺移植术前评估与术后并发症诊治，Email：juchunrong@126.com

中图分类号: R617, R457.2
计量
- 文章访问数: 329
- HTML全文浏览量: 117
- PDF下载量: 79
- 被引次数: 0
出版历程
- 收稿日期: 2022-03-23
- 网络出版日期: 2022-07-14
- 刊出日期: 2022-07-15

Protein A immunoadsorption in the treatment of de novo DSA-mediated acute rejection after lung transplantation

The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, Guangzhou 510012, China

More Information

Corresponding author: Ju Chunrong, Email: juchunrong@126.com

摘要

摘要: 目的探讨肺移植术后新生供者特异性抗体(dnDSA)介导的急性排斥反应的治疗方法。方法回顾性分析1例肺移植术后早期出现抗体介导的急性排斥反应(AMR)受者的资料，分析其诊疗经过。结果受者因系统性硬化症相关性终末期间质性肺病接受右肺移植，术前群体反应性抗体(PRA)Ⅰ类阳性(11%)，术前未行特殊预处理，手术当日及术后予以抗胸腺细胞球蛋白诱导治疗。术后早期受者康复顺利，术后13 d出现胸闷、气促，并呈进行性加重，迅速进展为Ⅰ型呼吸衰竭，PRA Ⅰ类上升为58%，并出现dnDSA，其位点为A24：02，平均荧光强度(MFI)值为2 110，据国际心肺移植学会指南，拟诊为(可能)AMR。予血浆置换、蛋白A免疫吸附、糖皮质激素冲击、利妥昔单抗及免疫球蛋白静脉滴注等综合治疗后，PRA及DSA水平逐渐下降，术后20 d DSA MFI值为0，受者临床情况逐渐好转，呼吸困难消失，气促逐渐缓解，呼吸衰竭纠正，肺部渗出影逐渐吸收；术后45 d，受者完全康复出院。随访1年，受者状态良好，生活质量与同龄健康人相同，PRA Ⅰ类为5%，Ⅱ类为阴性，未出现DSA。结论在传统药物治疗基础上加用蛋白A免疫吸附治疗，能有效去除受者循环血液中的DSA，减轻靶器官损害，近期及远期治疗效果理想。针对肺移植术后AMR，采用传统药物治疗联合免疫吸附，可以达到理想治疗效果。
- 肺移植 /
- 抗体介导的排斥反应 /
- 血浆置换 /
- 免疫吸附 /
- 供者特异性抗体(DSA) /
- 群体反应性抗体 /
- 抗胸腺细胞球蛋白 /
- 糖皮质激素
Abstract: Objective To investigate the treatment on de novo donor specific antibody (dnDSA) mediated acute rejection after lung transplantation. Methods Clinical data of 1 recipient with antibody-mediated rejection (AMR) early after lung transplantation was retrospectively analyzed. The process of diagnosis and treatment were assessed. Results The recipient underwent right lung transplantation due to systemic sclerosis-associated end-stage interstitial lung disease. Preoperatively, classⅠ panel reactive antibody (PRA) was positive (11%). No pretreatment was given before transplantation. Antithymocyte globulin induction therapy was delivered on the day of transplantation and postoperatively. The recipient was properly recovered early after transplantation. Chest tightness and shortness of breath occurred at postoperative 13 d, which were progressively worsened and rapidly progressed into type Ⅰ respiratory failure. Class Ⅰ PRA was increased to 58%, and dnDSA was observed at the loci of A24: 02. The mean fluorescence intensity (MFI) was 2 110. According to the guidelines of International Society for Heart and Lung Transplantation, the recipient was diagnosed as possible AMR. After comprehensive treatment including plasmapheresis, protein A immunoadsorption, glucocorticoid pulse, rituximab and immunoglobulin intravenous drip, the PRA and DSA levels were gradually decreased, and the MFI of DSA was 0 at postoperative 20 d. Clinical condition of the recipient was gradually improved. The dyspnea was healed, shortness of breath was eased, respiratory failure was treated, and pulmonary effusion was gradually absorbed. At postoperative 45 d, the recipient was discharged after full recovery. During 1-year follow-up, the recipient was physically stable and obtained normal quality of life. Class Ⅰ PRA was 5%, and class Ⅱ PRA was negative. No DSA was noted. Conclusions Based on traditional drug therapy, supplement of protein A immunoadsorption therapy may effectively eliminate DSA from the circulating blood of the recipient and mitigate the damage of target organs. Ideal short- and long-term prognosis may be achieved. Traditional drug therapy combined with immunoadsorption may yield ideal efficacy in treating AMR after lung transplantation.
- Lung transplantation /
- Antibody-mediated rejection /
- Plasmapheresis /
- Immunoadsorption /
- Donor specific antibody (DSA) /
- Panel reactive antibody /
- Antithymocyte globulin /
- Glucocorticoid

HTML全文

下载: 全尺寸图片幻灯片

图 1 肺移植受者的胸部X线表现

注：A图为肺移植术后12 d的胸部X线表现；B图为肺移植术后21 d，出现AMR相关临床表现时的胸部X线表现，可见右侧移植肺渗出性病变较前明显增多。

Figure 1. Chest X-ray findings of the lung transplant recipient

下载: 全尺寸图片幻灯片

图 2 肺移植受者胸部CT表现

注：A图为肺移植术前的CT图像；B图为肺移植术后13 d，出现ACR相关临床症状时的CT图像；C图为按照AMR进行治疗后复查的CT图像。

Figure 2. Chest CT findings of the lung transplant recipient

下载: 全尺寸图片幻灯片

参考文献(32)

[1]	GREER M, WERLEIN C, JONIGK D. Surveillance for acute cellular rejection after lung transplantation[J]. Ann Transl Med, 2020, 8(6): 410. DOI: 10.21037/atm.2020.02.127.
[2]	郭晖. 移植肺病理学诊断标准及其进展[J]. 器官移植, 2022, 13(1): 19-31. DOI: 10.3969/j.issn.1674-7445.2022.01.004. GUO H. Diagnostic criteria and research progress on lung allograft pathology[J]. Organ Transplant, 2022, 13(1): 19-31. DOI: 10.3969/j.issn.1674-7445.2022.01.004.
[3]	SUBRAMANI MV, PANDIT S, GADRE SK. Acute rejection and post lung transplant surveillance[J]. Indian J Thorac Cardiovasc Surg, 2022, DOI: 10.1007/s12055-021-01320-z[Epubaheadofprint].
[4]	OHM B, JUNGRAITHMAYR W. B cell immunity in lung transplant rejection - effector mechanisms and therapeutic implications[J]. Front Immunol, 2022, 13: 845867. DOI: 10.3389/fimmu.2022.845867..
[5]	PARULEKAR AD, KAO CC. Detection, classification, and management of rejection after lung transplantation[J]. J Thorac Dis, 2019, 11(Suppl 14): S1732-S1739. DOI: 10.21037/jtd.2019.03.83.
[6]	YOUNG KA, ALI HA, BEERMANN KJ, et al. Lung Transplantation and the era of the sensitized patient[J]. Front Immunol, 2021, 12: 689420. DOI: 10.3389/fimmu.2021.689420.
[7]	WITT CA, GAUT JP, YUSEN RD, et al. Acute antibody-mediated rejection after lung transplantation[J]. J Heart Lung Transplant, 2013, 32(10): 1034-1040. DOI: 10.1016/j.healun.2013.07.004.
[8]	BRUGIÈRE O, SUBERBIELLE C, THABUT G, et al. Lung transplantation in patients with pretransplantation donor-specific antibodies detected by Luminex assay[J]. Transplantation, 2013, 95(5): 761-765. DOI: 10.1097/TP.0b013e31827afb0f.
[9]	BERY AI, HACHEM RR. Antibody-mediated rejection after lung transplantation[J]. Ann Transl Med, 2020, 8(6): 411. DOI: 10.21037/atm.2019.11.86.
[10]	DEL ANGEL-PABLO AD, BUENDÍA-ROLDÁN I, MEJÍA M, et al. Anti-HLA class Ⅱ antibodies correlate with C-reactive protein levels in patients with rheumatoid arthritis associated with interstitial lung disease[J]. Cells, 2020, 9(3): 691. DOI: 10.3390/cells9030691.
[11]	GOCHI F, CHEN-YOSHIKAWA TF, KAYAWAKE H, et al. Comparison of de novo donor-specific antibodies between living and cadaveric lung transplantation[J]. J Heart Lung Transplant, 2021, 40(7): 607-613. DOI: 10.1016/j.healun.2021.03.019.
[12]	HOGEN R, DINORCIA J, DHANIREDDY K. Antibody-mediated rejection: what is the clinical relevance?[J]. Curr Opin Organ Transplant, 2017, 22(2): 97-104. DOI: 10.1097/MOT.0000000000000391.
[13]	TIKKANEN JM, SINGER LG, KIM SJ, et al. De novo DQ donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation[J]. Am J Respir Crit Care Med, 2016, 194(5): 596-606. DOI: 10.1164/rccm.201509-1857OC.
[14]	LEVINE DJ, GLANVILLE AR, ABOYOUN C, et al. Antibody-mediated rejection of the lung: a consensus report of the International Society for Heart and Lung Transplantation[J]. J Heart Lung Transplant, 2016, 35(4): 397-406. DOI: 10.1016/j.healun.2016.01.1223.
[15]	SIS B. Endothelial molecules decipher the mechanisms and functional pathways in antibody-mediated rejection[J]. Hum Immunol, 2012, 73(12): 1218-1225. DOI: 10.1016/j.humimm.2012.07.332.
[16]	TSAI EW, REED EF. MHC class I signaling: new functional perspectives for an old molecule[J]. Tissue Antigens, 2014, 83(6): 375-381. DOI: 10.1111/tan.12381.
[17]	VALENZUELA NM, MCNAMARA JT, REED EF. Antibody-mediated graft injury: complement-dependent and complement-independent mechanisms[J]. Curr Opin Organ Transplant, 2014, 19(1): 33-40. DOI: 10.1097/MOT.0000000000000040.
[18]	ROUX A, LEVINE DJ, ZEEVI A, et al. Banff lung report: current knowledge and future research perspectives for diagnosis and treatment of pulmonary antibody-mediated rejection (AMR)[J]. Am J Transplant, 2019, 19(1): 21-31. DOI: 10.1111/ajt.14990.
[19]	HULBERT AL, PAVLISKO EN, PALMER SM. Current challenges and opportunities in the management of antibody-mediated rejection in lung transplantation[J]. Curr Opin Organ Transplant, 2018, 23(3): 308-315. DOI: 10.1097/MOT.0000000000000537.
[20]	HALVERSON LP, HACHEM RR. Antibody-mediated rejection and lung transplantation[J]. Semin Respir Crit Care Med, 2021, 42(3): 428-435. DOI: 10.1055/s-0041-1728796.
[21]	HACHEM RR, YUSEN RD, MEYERS BF, et al. Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation[J]. J Heart Lung Transplant, 2010, 29(9): 973-980. DOI: 10.1016/j.healun.2010.05.006.
[22]	NEUHAUS K, HOHLFELDER B, BOLLINGER J, et al. Antibody-mediated rejection management following lung transplantation[J]. Ann Pharmacother, 2022, 56(1): 60-64. DOI: 10.1177/10600280211012410.
[23]	PHAM C, PIERCE BJ, NGUYEN DT, et al. Assessment of carfilzomib treatment response in lung transplant recipients with antibody-mediated rejection[J]. Transplant Direct, 2021, 7(4): e680. DOI: 10.1097/TXD.0000000000001131.
[24]	MULLER YD, AUBERT JD, VIONNET J, et al. Acute antibody-mediated rejection 1 week after lung transplantation successfully treated with eculizumab, intravenous immunoglobulins, and rituximab[J]. Transplantation, 2018, 102(6): e301-e303. DOI: 10.1097/TP.0000000000002165.
[25]	TIMOFEEVA OA, CHOE J, ALSAMMAK M, et al. Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study[J]. Transpl Int, 2021, 34(4): 700-708. DOI: 10.1111/tri.13825.
[26]	KÄLBLE F, SÜSAL C, PEGO DA SILVA L, et al. Living donor kidney transplantation in patients with donor-specific HLA antibodies after desensitization with immunoadsorption[J]. Front Med (Lausanne), 2021, 8: 781491. DOI: 10.3389/fmed.2021.781491.
[27]	KULKARNI HS, BEMISS BC, HACHEM RR. Antibody-mediated rejection in lung transplantation[J]. Curr Transplant Rep, 2015, 2(4): 316-323. DOI: 10.1007/s40472-015-0074-5.
[28]	SWEET SC, ARMSTRONG B, BLATTER J, et al. CTOTC-08: a multicenter randomized controlled trial of rituximab induction to reduce antibody development and improve outcomes in pediatric lung transplant recipients[J]. Am J Transplant, 2022, 22(1): 230-244. DOI: 10.1111/ajt.16862.
[29]	BÖHMIG GA, REGELE H, EXNER M, et al. C4d-positive acute humoral renal allograft rejection: effective treatment by immunoadsorption[J]. J Am Soc Nephrol, 2001, 12(11): 2482-2489. DOI: 10.1681/ASN.V12112482.
[30]	FUCHS K, RUMMLER S, RIES W, et al. Performance, clinical effectiveness, and safety of immunoadsorption in a wide range of indications[J]. Ther Apher Dial, 2022, 26(1): 229-241. DOI: 10.1111/1744-9987.13663.
[31]	姬芳玲, 吴健, 贾凌云. 免疫吸附治疗自身免疫疾病的研究进展[J]. 生物化学与生物物理进展, 2022, 49(1): 139-148. DOI: 10.16476/j.pibb.2021.0384. JI FL, WU J, JIA LY. Research progress of immunoadsorption in the treatment of autoimmune diseases: a review[J]. Prog Biochem Biophys, 2022, 49(1): 139-148. DOI: 10.16476/j.pibb.2021.0384.
[32]	张政, 蒙兴文, 钟小凤, 等. 免疫吸附治疗类风湿关节炎的应用综述[J]. 当代医学, 2021, 27(25): 193-194. DOI: 10.3969/j.issn.1009-4393.2021.25.085. ZHANG Z, MENG XW, ZHONG XF, et al. A review of the application of immunosorbent in the treatment of rheumatoid arthritis[J]. Contemp Med, 2021, 27(25): 193-194. DOI: 10.3969/j.issn.1009-4393.2021.25.085.