IgG亚类分子生物学特性及在相关疾病临床应用的研究进展

张胜; 曹君; 金婕妤; 梁玉婷

doi:10.16766/j.cnki.issn.1674-4152.003261

IgG亚类分子生物学特性及在相关疾病临床应用的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.003261

苏州大学附属第一医院临床检测中心，江苏苏州 215006

基金项目:

国家自然科学基金青年科学基金项目 81901632

详细信息

通讯作者:
梁玉婷，E-mail：liangyuting666@126.com

中图分类号: R593
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- 被引次数: 0
出版历程
- 收稿日期: 2022-06-17
- 网络出版日期: 2024-01-13

Research progress on molecular biological characteristics of IgG subclasses and its clinical application in related diseases

Center for Clinical Laboratory, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China

摘要

摘要: 免疫球蛋白(immunoglobulin，Ig)是B淋巴细胞在抗原刺激下转化为浆细胞，进而产生能与相应抗原发生特异性结合的抗体，是适应性免疫系统分泌的一种糖蛋白，在体液免疫中发挥重要作用，包括免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、免疫球蛋白E(IgE)和免疫球蛋白D(IgD)。其中IgG是血清中免疫球蛋白的主要成分，是人体血清和细胞外液中含量最高、半衰期最长的免疫球蛋白类型。IgG是人体内最主要的抗体，具有抗菌、抗病毒感染、中和毒素及免疫调节的功能，同时也是唯一能通过胎盘在新生儿抗感染中起重要作用的类型。根据重链抗原性和二硫键的数目不同，IgG又可分IgG1、IgG2、IgG3、IgG4四个亚类, IgG不同亚型的整体结构类似，但其结合辅助分子和受体的重要结构差异可发挥不同的生物学功能，如抗原抗体识别、补体激活及细胞表面受体特异性结合等。鉴于IgG各亚类重链铰链区氨基酸序列不同，4种IgG亚类抗体在不同的临床疾病进展过程中发挥的功能不同。目前已有相关研究显示IgG亚类在自身免疫性疾病、感染性疾病、变态反应性疾病等疾病中具有重要的临床应用价值，故本文就IgG各亚类分子特征和生物学作用及其与临床疾病的相关性进行综述，为临床相关疾病的发病机制研究及诊疗和疾病预后监测提供新的思路和视角。
- 免疫球蛋白G /
- 免疫球蛋白G亚类 /
- 自身免疫病 /
- 免疫缺陷病
Abstract: Immunoglobulin (Ig) is a glycoprotein secreted by the adaptive immune system, which plays an important role in humoral immunity, including immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin E (IgE), and immunoglobulin D (IgD). Among them, IgG is the main component of immunoglobulin in serum, and it is the type of immunoglobulin with the highest content and longest half-life in human serum and extracellular fluid. IgG is the most important antibody in the human body, which has the functions of antibacterial, antiviral infection, neutralizing toxin and immune regulation. It is also the only type that can pass the placenta and play an important role in neonatal anti-infection. According to the number of heavy chain antigenicity and disulfide bond, IgG points IgG1, IgG2, IgG3, IgG4 four subgroups, the structure of the different subtypes is similar, but the combination of helpers and receptors important structural differences can produce different biological functions, such as recognition of antigen-antibody, complement activation and cell surface receptor specificity combined. In view of the different amino acid sequences in the hinge region of the heavy chain of each IgG subclass, the four IgG subclass antibodies play different functions in different clinical disease progression. At present, relevant studies have shown that IgG subclasses have important clinical application value in autoimmune diseases, infectious diseases, allergic diseases and other diseases. Therefore, this article reviews the molecular characteristics and biological effects of IgG subclasses and their correlation with clinical diseases. It provides new ideas and perspectives for the study of pathogenesis, diagnosis, treatment and prognostic monitoring of clinically related diseases.
- Immunoglobulin G /
- Immunoglobulin G subclasses /
- Autoimmune diseases /
- Immunodeficiency

HTML全文

图 1 IgG和不同IgG亚类的结构^[2]

注：A示IgG结构的Fab段和Fc段的结构域不同，图中还显示了恒定区(C)和可变区(V)；B示4种IgG亚型。

Figure 1. Structure of IgG and different IgG subclasses^[2]

下载: 全尺寸图片幻灯片

参考文献(40)

[1]	ROOPENIAN D C, AKILESH S. FcRn: the neonatal Fc receptor comes of age[J]. Nat Rev Immunol, 2007, 7(9): 715-725. doi: 10.1038/nri2155
[2]	NAPODANO C, MARINO M, STEFANILE A, et al. Immunological role of IgG subclasses[J]. Immunol Invest, 2021, 50(4): 427-444. doi: 10.1080/08820139.2020.1775643
[3]	LUDWIG-KRAUS B, KRAUS F B. Similar but not consistent: revisiting the pitfalls of measuring IgG subclasses with different assays[J]. J Clin Lab Anal, 2017, 31(6): e22146. DOI: 10.1002/jcla.22146.
[4]	LIU Z J, DENG C W, LI P, et al. A reference interval for serum IgG subclasses in Chinese children[J]. PLoS One, 2018, 13(3): e0192923. DOI: 10.1371/journal.pone.0192923.
[5]	LADWIG P M, BARNIDGE D R, SNYDER M R, et al. Quantification of serum IgG subclasses by use of subclass-specific tryptic peptides and liquid chromatography: tandem mass spectrometry[J]. Clin Chem, 2014, 60(8): 1080-1088. doi: 10.1373/clinchem.2014.222208
[6]	SIGAL L H. Basic science for the clinician 58: IgG subclasses[J]. J Clin Rheumatol, 2012, 18(6): 316-318. doi: 10.1097/RHU.0b013e318269446b
[7]	BONDT A, HOEK M, TAMARA S, et al. Human plasma IgG1 repertoires are simple, unique, and dynamic[J]. Cell Syst, 2021, 12(12): 1131-1143. doi: 10.1016/j.cels.2021.08.008
[8]	SCHUR P H. IgG subclasses: a review[J]. Ann Allergy, 1987, 58(2): 89-96, 99.
[9]	BARTON J, BARTON C, BERTOLI L. Duration of frequent or severe respiratory tract infection in adults before diagnosis of IgG subclass deficiency[J]. PLoS One, 2019, 14(5): e0216940. DOI: 10.1371/journal.pone.0216940.
[10]	MOLICA S. Infections in chronic lymphocytic leukemia: risk factors, and impact on survival, and treatment[J]. Leuk Lymphoma, 1994, 13(3-4): 203-214. doi: 10.3109/10428199409056283
[11]	CRASSINI K R, ZHANG E, BALENDRAN S, et al. Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in chronic lymphocytic leukaemia[J]. Br J Haematol, 2018, 181(1): 97-101. doi: 10.1111/bjh.15146
[12]	PASTORI C, GALLI L, SIRACUSANO G, et al. Serum IgG1 and IgG4 could contribute to partial control of viral rebound in chronically HIV-1-infected patients[J]. AIDS, 2021, 35(10): 1549-1559. doi: 10.1097/QAD.0000000000002944
[13]	ZHANG H Z, LI P, WU D, et al. Serum IgG subclasses in autoimmune diseases[J]. Medicine (Baltimore), 2015, 94(2): e387. DOI: 10.1097/MD.0000000000000387.
[14]	BASILE U, MARINO M, NAPODANO C, et al. Serological immunoglobulin-free light chain profile in myasthenia gravis patients[J]. J Immunol Res, 2018: 9646209. DOI: 10.1155/2018/9646209.
[15]	BARTON J C, BARTON J C, BERTOLI L F, et al. Characterization of adult patients with IgG subclass deficiency and subnormal IgG2[J]. PLoS One, 2020, 15(10): e0240522. DOI: 10.1371/journal.pone.0240522.
[16]	LEITAO FILHO F S, RA S W, MATTMAN A, et al. Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD[J]. Respir Res, 2018, 19(1): 30. doi: 10.1186/s12931-018-0733-z
[17]	YAMAZAKI R, KATO J, KODA Y, et al. Impact of immunoglobulin G2 subclass level on late-onset bacterial infection after allogeneic hematopoietic stem cell transplantation[J]. Transpl Infect Dis, 2019, 21(3): e13086. DOI: 10.1111/tid.13086.
[18]	YAMAZAKI R, KIKUCHI T, KATO J, et al. Recurrent bacterial pneumonia due to immunoglobulin G2 subclass deficiency after allogeneic hematopoietic stem cell transplantation: efficacy of immunoglobulin replacement[J]. Transpl Infect Dis, 2018, 20(3): e12863. DOI: 10.1111/tid.12863.
[19]	XIE L D, GAO Y, LI M R, et al. Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashimoto ' s thyroiditis with different thyroid functional status[J]. Clin Exp Immunol, 2008, 154(2): 172-176. doi: 10.1111/j.1365-2249.2008.03756.x
[20]	KAWANO Y, NOMA T, YATA J. Regulation of human IgG subclass production by cytokines. IFN-gamma and IL-6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2[J]. J Immunol, 1994, 153(11): 4948-4958.
[21]	ENGELHART S, GLYNN R J, SCHUR P H. Disease associations with isolated elevations of each of the four IgG subclasses[J]. Semin Arthritis Rheum, 2017, 47(2): 276-280. doi: 10.1016/j.semarthrit.2017.03.021
[22]	HUSSAIN R, JAFERI W, ZUBERI S, et al. Significantly increased IgG2 subclass antibody levels to Blastocystis hominis in patients with irritable bowel syndrome[J]. Am J Trop Med Hyg, 1997, 56(3): 301-306. doi: 10.4269/ajtmh.1997.56.301
[23]	VIDARSSON G, DEKKERS G, RISPENS T. IgG subclasses and allotypes: from structure to effector functions[J]. Front Immunol, 2014, 5: 520. DOI: 10.3389/fimmu.2014.00520.
[24]	ZENG Y L, ZHANG Y, CHEN Q G, et al. Distribution of IgG subclass anti-nuclear antibodies (ANAs) in systemic lupus erythematosus[J]. Lupus, 2021, 30(6): 901-912. doi: 10.1177/0961203321995242
[25]	GULLI F, BASILE U, GRAGNANI L, et al. IgG cryoglobulinemia[J]. Eur Rev Med Pharmacol Sci, 2018, 22(18): 6057-6062.
[26]	GULLI F, BASILE U, GRAGNANI L, et al. Autoimmunity and lymphoproliferation markers in naïve HCV-RNA positive patients without clinical evidences of autoimmune/lymphoproliferative disorders[J]. Dig Liver Dis, 2016, 48(8): 927-933.
[27]	RIGOPOULOU E I, DAVIES E T, BOGDANOS D P, et al. Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis[J]. Liver Int, 2007, 27(9): 1226-1231. doi: 10.1111/j.1478-3231.2007.01586.x
[28]	RIGOPOULOU E I, DAVIES E T, PARES A, et al. Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis[J]. Gut, 2005, 54(4): 528-532. doi: 10.1136/gut.2003.036558
[29]	KONECZNY I. Update on IgG4-mediated autoimmune diseases: new insights and new family members[J]. Autoimmun Rev, 2020, 19(10): 102646. DOI: 10.1016/j.autrev.2020.102646.
[30]	TAKAHASHI H, YAMAMOTO M, SUZUKI C, et al. The birthday of a new syndrome: IgG4-related diseases constitute a clinical entity[J]. Autoimmun Rev, 2010, 9(9): 591-594. doi: 10.1016/j.autrev.2010.05.003
[31]	SHIMOSEGAWA T, CHARI S T, FRULLONI L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology[J]. Pancreas, 2011, 40(3): 352-358. doi: 10.1097/MPA.0b013e3182142fd2
[32]	UMEHARA H, OKAZAKI K, KAWANO M, et al. How to diagnose IgG4-related disease[J]. Ann Rheum Dis, 2017, 76(11): e46. DOI: 10.1136/annrheumdis-2017-211330.
[33]	DEMIR A M, AYDIN F, ACAR B, et al. IgG4-related disease and ANCA positive vasculitis in childhood: a case-based review[J]. Clin Rheumatol, 2021, 40(9): 3817-3825. doi: 10.1007/s10067-021-05635-5
[34]	MICHAILIDOU D, SCHWARTZ D M, MUSTELIN T, et al. Allergic aspects of IgG4-related disease: implications for pathogenesis and therapy[J]. Front Immunol, 2021, 12: 693192. DOI: 10.3389/fimmu.2021.693192.
[35]	MÍNGUEZ SABATER A, LADRÓN ABIA P, HIGÓN BALLESTER M D. IgG4 autoimmune sclerosing cholangitis[J]. Med Clin (Barc), 2021, 156(8): 414-415. doi: 10.1016/j.medcli.2020.01.010
[36]	ARYASIT O, TIRASET N, PREECHAWAI P, et al. IgG4-related disease in patients with idiopathic orbital inflammation[J]. BMC Ophthalmol, 2021, 21(1): 356. doi: 10.1186/s12886-021-02115-x
[37]	MOMONIAT T, JACOB D, DUHLI N, et al. IgG4-related tubulointerstitial nephritis[J]. BMJ Case Rep, 2021, 14(11): e241942. DOI: 10.1136/bcr-2021-241942.
[38]	CHEN L F, MO Y Q, MA J D, et al. Elevated serum IgG4 defines specific clinical phenotype of rheumatoid arthritis[J]. Mediators Inflamm, 2014, 2014: 635293. DOI: 10.1155/2014/635293.
[39]	SAKTHISWARY R, SHAHARIR S S, WAHAB A A. Frequency and clinical significance of elevated IgG4 in rheumatoid arthritis: a systematic review[J]. Biomedicines, 2022, 10(3): 558. doi: 10.3390/biomedicines10030558
[40]	KOERS J, DERKSEN N, FALKENBURG W, et al. Elevated Fab glycosylation of anti-hinge antibodies[J]. Scand J Rheumatol, 2021, 11: 1-8.