静脉注射免疫球蛋白的作用机制及在肾移植中的应用

欧志宇; 贺裕; 苗芸

doi:10.3969/j.issn.1674-7445.2021.03.015

静脉注射免疫球蛋白的作用机制及在肾移植中的应用

doi: 10.3969/j.issn.1674-7445.2021.03.015

510515 广州，南方医科大学第一临床医学院（欧志宇、贺裕）；南方医院器官移植科（苗芸）

基金项目:

国家自然科学基金 82070770

广东省自然科学基金 2020A1515010674

广州市科技计划项目 201803010109

南方医院院长基金 2018B009

南方医院院长基金 2018C003

大学生创新创业训练计划项目 202012121046

大学生创新创业训练计划项目 X202012121239

详细信息

作者简介:
欧志宇，男，1997年生，博士研究生，研究方向为肾移植，Email：ouzhiyu15@163.com

通讯作者:
苗芸，女，1978年生，博士，主任医师，研究方向为肾移植，Email：miaoyunecho@126.com

中图分类号: R617, R977.8
计量
- 文章访问数: 1477
- HTML全文浏览量: 591
- PDF下载量: 154
- 被引次数: 0
出版历程
- 收稿日期: 2021-01-20
- 网络出版日期: 2021-05-19
- 刊出日期: 2021-05-15

Mechanism of intravenous immunoglobulin and its application in renal transplantation

First Clinical Medicine College, Southern Medical University, Guangzhou 510515, China

More Information

Corresponding author: Miao Yun, Email: miaoyunecho@126.com

摘要

摘要: 静脉注射免疫球蛋白（IVIG）是从健康人血浆中分离得到的免疫球蛋白（Ig），其主要成分是IgG。IVIG作用机制复杂，可以通过多种途径发挥作用，如IgG的Fc段与多种Fc段γ受体（FcγR）结合调控炎症反应以及自身抗体代谢，IgG的Fab段中和多种抗原和其它分子，IVIG还可以阻碍补体激活、影响免疫细胞间抑炎和促炎平衡。IVIG在疾病治疗中常通过多种机制同时发挥作用，并在不同疾病中以某一种机制为主。IVIG在肾移植中常用于致敏患者的脱敏治疗、ABO血型不相容肾移植、抗体介导的排斥反应以及部分感染性疾病的治疗。本文对IVIG的作用机制及其在肾移植中的应用做一综述。
- 免疫球蛋白 /
- 肾移植 /
- 免疫调节 /
- 免疫复合物 /
- 抗体介导的排斥反应 /
- 血浆置换 /
- BK病毒相关性肾病 /
- 人类细小病毒B19
Abstract: Intravenous immunoglobulin (IVIG) is an immunoglobulin (Ig) isolated from the plasma of healthy human, and its main component is IgG. The mechanism of IVIG is complex, which may play a role via multiple pathways. For example, the combination of Fc fragment of IgG with various Fc gamma receptor (FcγR) regulates inflammatory response and autoantibody metabolism, and Fab fragment of IgG neutralizes multiple antigens and other molecules. IVIG may also inhibit complement activation and affect the balance of anti-inflammation and proinflammation among immune cells. In the treatment of diseases, IVIG constantly plays a role through multiple mechanisms simultaneously, primarily via one certain mechanism in different diseases. IVIG is commonly applied in the desensitization treatment of sensitized patients, ABO incompatible renal transplantation, antibody-mediated rejection and several infectious diseases. In this article, the mechanism of IVIG and its application in renal transplantation were reviewed.
- Immunoglobulin /
- Renal transplantation /
- Immune regulation /
- Immune complex /
- Antibody-mediated rejection /
- Plasmapheresis /
- BK virus-associated nephropathy /
- Human parvovirus B19

HTML全文

下载: 全尺寸图片幻灯片

图 1 IgG分子结构及其介导的作用机制

Figure 1. Molecular structure of IgG and its mediating mechanism

下载: 全尺寸图片幻灯片

参考文献(40)

[1]	邱晓, 罗建辉. 静脉注射人免疫球蛋白生产工艺、质量控制的演变及评价思考[J]. 中国生物制品学杂志, 2020, 33(11), 1336-1339. https://www.cnki.com.cn/Article/CJFDTOTAL-SWZP202011022.htm QIU X, LUO JH. Evolution and evaluation of production technology and quality control of human intravenous immunoglobulin[J]. Chin J Biol, 2020, 33(11), 1336-1339. https://www.cnki.com.cn/Article/CJFDTOTAL-SWZP202011022.htm
[2]	孙盼, 马莉, 刁戈, 等. 国内7个厂家静注人免疫球蛋白产品成分分析[J]. 中国输血杂志, 2014, 27(1): 40-42. DOI: 10.13303/j.cjbt.issn.1004-549x.2014.01.015. SUN P, MA L, DIAO G, et al. Composition analysis of intravenous immunoglobulin from seven Chinese blood fractionation industries[J]. Chin J Blood Transfus, 2014, 27(1): 40-42. DOI: 10.13303/j.cjbt.issn.1004-549x.2014. 01.015.
[3]	ERMAKOV EA, NEVINSKY GA, BUNEVA VN. Immunoglobulins with non-canonical functions in inflammatory and autoimmune disease states[J]. Int J Mol Sci, 2020, 21(15): 5392. DOI: 10.3390/ijms21155392.
[4]	DOU X, YANG R. Current and emerging treatments for immune thrombocytopenia[J]. Expert Rev Hematol, 2019, 12(9): 723-732. DOI: 10.1080/17474086.2019.1636644.
[5]	GELFAND EW. Intravenous immune globulin in autoimmune and inflammatory diseases[J]. N Engl J Med, 2012, 367(21): 2015-2025. DOI: 10.1056/NEJMra1009433.
[6]	DALAKAS MC, SPAETH PJ. The importance of FcRn in neuro-immunotherapies: from IgG catabolism, FCGRTgene polymorphisms, IVIG dosing and efficiency to specificFcRn inhibitors[J]. Ther Adv Neurol Disord, 2021, 14: 1756286421997381. DOI: 10.1177/1756286421997381.
[7]	VERBOON C, VAN DEN BERG B, CORNBLATH DR, et al. Original research: second IVIG course in Guillain-Barré syndrome with poor prognosis: the non-randomised ISID study[J]. J Neurol Neurosurg Psychiatry, 2020, 91(2): 113-121. DOI: 10.1136/jnnp-2019-321496.
[8]	KARNAM A, RAMBABU N, DAS M, et al. Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells[J]. Commun Biol, 2020, 3(1): 96. DOI: 10.1038/s42003-020-0825-4.
[9]	TRINATH J, HEGDE P, SHARMA M, et al. Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E₂ in human dendritic cells[J]. Blood, 2013, 122(8): 1419-1427. DOI: 10.1182/blood-2012-11-468264.
[10]	NAGELKERKE SQ, KUIJPERS TW. Immunomodulation by IVIG and the role of Fc-Gamma receptors: classic mechanisms of action after all?[J]. Front Immunol, 2015, 5: 674. DOI: 10.3389/fimmu.2014.00674.
[11]	HEITINK-POLLÉ KMJ, UITERWAAL CSPM, PORCELIJN L, et al. Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial[J]. Blood, 2018, 132(9): 883-891. DOI: 10.1182/blood-2018-02-830844.
[12]	GOLDBERG BS, ACKERMAN ME. Antibody-mediated complement activation in pathology and protection[J]. Immunol Cell Biol, 2020, 98(4): 305-317. DOI: 10.1111/imcb.12324.
[13]	LUTZ HU, SPÄTH PJ. Anti-inflammatory effect of intravenous immunoglobulin mediated through modulation of complement activation[J]. Clin Rev Allergy Immunol, 2005, 29(3): 207-212. DOI: 10.1385/CRIAI:29:3:207.
[14]	WASSERMAN RL, LUMRY W, HARRIS J 3RD, et al. Efficacy, safety, and pharmacokinetics of a new 10% liquid intravenous immunoglobulin containing high titer neutralizing antibody to RSV and other respiratory viruses in subjects with primary immunodeficiency disease[J]. J Clin Immunol, 2016, 36(6): 590-599. DOI: 10.1007/s10875-016-0308-z.
[15]	EL-HUSSEINI A, AGHIL A, RAMIREZ J, et al. Outcome of kidney transplant in primary, repeat, and kidney-after-nonrenal solid-organ transplantation: 15-year analysis of recent UNOS database[J]. Clin Transplant, 2017, 31(11). DOI: 10.1111/ctr.13108.
[16]	MONTGOMERY RA, LONZE BE, KING KE, et al. Desensitization in HLA-incompatible kidney recipients and survival[J]. N Engl J Med, 2011, 365(4): 318-326. DOI: 10.1056/NEJMoa1012376.
[17]	BUJNOWSKA A, MICHON M, KONOPELSKI P, et al. Outcomes of prolonged treatment with intravenous immunoglobulin infusions for acute antibody-mediated rejection in kidney transplant recipients[J]. Transplant Proc, 2018, 50(6): 1720-1725. DOI: 10.1016/j.transproceed.2018.02.110.
[18]	MORESO F, CRESPO M, RUIZ JC, et al. Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: a multicenter, prospective, randomized, double-blind clinical trial[J]. Am J Transplant, 2018, 18(4): 927-935. DOI: 10.1111/ajt.14520.
[19]	SCURT FG, EWERT L, MERTENS PR, et al. Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and Meta-analysis[J]. Lancet, 2019, 393(10185): 2059-2072. DOI: 10.1016/S0140-6736(18)32091-9.
[20]	HUSSAIN I, TASNEEM F, GILANI US, et al. Human BK and JC polyomaviruses: molecular insights and prevalence in Asia[J]. Virus Res, 2020, 278: 197860. DOI: 10.1016/j.virusres.2020.197860.
[21]	YOOPRASERT P, ROTJANAPAN P. BK virus-associated nephropathy: current situation in a resource-limited country[J]. Transplant Proc, 2018, 50(1): 130-136. DOI: 10.1016/j.transproceed.2017.11.007.
[22]	VU D, SHAH T, ANSARI J, et al. Efficacy of intravenous immunoglobulin in the treatment of persistent BK viremia and BK virus nephropathy in renal transplant recipients[J]. Transplant Proc, 2015, 47(2): 394-398. DOI: 10.1016/j.transproceed.2015.01.012.
[23]	KABLE K, DAVIES CD, O'CONNELL PJ, et al. Clearance of BK virus nephropathy by combination antiviral therapy with intravenous immunoglobulin[J]. Transplant Direct, 2017, 3(4): e142. DOI: 10.1097/TXD.0000000000000641.
[24]	THONGPRAYOON C, KHOURY NJ, BATHINI T, et al. Epidemiology of parvovirus B19 and anemia among kidney transplant recipients: a Meta-analysis[J]. Urol Ann, 2020, 12(3): 241-247. DOI: 10.4103/UA.UA_89_19.
[25]	RINKŪNAITĖ I, ŠIMOLIŪNAS E, BIRONAITĖ D, et al. The effect of a unique region of parvovirus B19 capsid protein VP1 on endothelial cells[J]. Biomolecules, 2021, 11(4): 606. DOI: 10.3390/biom11040606.
[26]	MODROF J, BERTING A, TILLE B, et al. Neutralization of human parvovirus B19 by plasma and intravenous immunoglobulins[J]. Transfusion, 2008, 48(1): 178-186. DOI: 10.1111/j.1537-2995.2007.01503.x.
[27]	MASCIA G, ARGIOLAS D, CARTA E, et al. Successful treatment of anemia with anaplastic and microangiopathic characteristics in a kidney transplant recipient with parvovirus B19 infection: a case report[J]. Transplant Proc, 2020, 52(5): 1619-1622. DOI: 10.1016/j.transproceed.2020.02.077.
[28]	KAYA B, PAYDAS S. Recurrence of pure red cell aplasia in a kidney transplant recipient due to reactivation of parvovirus B19 infection despite two cycles of intravenous immunoglobulin therapy[J]. Exp Clin Transplant, 2019, 17(Suppl 1): 195-197. DOI: 10.6002/ect.MESOT2018.P63.
[29]	ROSADO-CANTO R, CARRILLO-PÉREZ DL, JIMÉNEZ JV, et al. Treatment strategies and outcome of parvovirus B19 infection in kidney transplant recipients: a case series and literature review of 128 patients[J]. Rev Invest Clin, 2019, 71(4): 265-274. DOI: 10.24875/RIC.19002921.
[30]	INOUE D, ODA T, IWAMA S, et al. Development of pure red cell aplasia by transmission and persistent infection of parvovirus B19 through a kidney allograft[J]. Transpl Infect Dis, 2021, 23(1): e13462. DOI: 10.1111/tid.13462.
[31]	BONAROS N, MAYER B, SCHACHNER T, et al. CMV-hyperimmune globulin for preventing cytomegalovirus infection and disease in solid organ transplant recipients: a Meta-analysis[J]. Clin Transplant, 2008, 22(1): 89-97. DOI: 10.1111/j.1399-0012.2007.00750.x.
[32]	MAJEED A, LATIF A, KAPOOR V, et al. Resistant cytomegalovirus infection in solid-organ transplantation: single-center experience, literature review of risk factors, and proposed preventive strategies[J]. Transplant Proc, 2018, 50(10): 3756-3762. DOI: 10.1016/j.transproceed.2018.02.091.
[33]	SANTHANAKRISHNAN K, YONAN N, CALLAN P, et al. The use of CMVIg rescue therapy in cardiothoracic transplantation: a single-center experience over 6 years (2011-2017)[J]. Clin Transplant, 2019, 33(8): e13655. DOI: 10.1111/ctr.13655.
[34]	NAIK AS, DHARNIDHARKA VR, SCHNITZLER MA, et al. Clinical and economic consequences of first-year urinary tract infections, sepsis, and pneumonia in contemporary kidney transplantation practice[J]. Transpl Int, 2016, 29(2): 241-252. DOI: 10.1111/tri.12711.
[35]	JARCZAK D, KLUGE S, NIERHAUS A. Use of intravenous immunoglobulins in sepsis therapy-a clinical view[J]. Int J Mol Sci, 2020, 21(15): 5543. DOI: 10.3390/ijms21155543.
[36]	TUTTLE K, MCDONALD M, ANDERSON E. Re-evaluating biologic pharmacotherapies that target the host response during sepsis[J]. Int J Mol Sci, 2019, 20(23): 6049. DOI: 10.3390/ijms20236049.
[37]	YANG Y, YU X, ZHANG F, et al. Evaluation of the effect of intravenous immunoglobulin dosing on mortality in patients with sepsis: a network Meta-analysis[J]. Clin Ther, 2019, 41(9): 1823-1838. DOI: 10.1016/j.clinthera.2019.06.010.
[38]	NIERHAUS A, BERLOT G, KINDGEN-MILLES D, et al. Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis[J]. Ann Intensive Care, 2020, 10(1): 132. DOI: 10.1186/s13613-020-00740-1.
[39]	SHANKAR-HARI M, MADSEN MB, TURGEON AF. Immunoglobulins and sepsis[J]. Intensive Care Med, 2018, 44(11): 1923-1925. DOI: 10.1007/s00134-018-5047-6.
[40]	PERRICONE C, TRIGGIANESE P, BURSI R, et al. Intravenous immunoglobulins at the crossroad of autoimmunity and viral infections[J]. Microorganisms, 2021, 9(1): 121. DOI: 10.3390/microorganisms9010121.