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It contributes to immune regulation by modulating antibody stability, half-life, and antigen-binding activity, as well as by mediating blocking antibody effects. This review highlights the expression patterns and potential mechanisms of Fab N-glycosylated IgG in autoimmune diseases, pregnancy-induced immune tolerance, and tumor immune evasion, and discusses its structural and functional similarities to IgG4. Although Fab N-glycosylation plays an important role in both physiological and pathological conditions, the complexity of its glycan structures and variability in glycosylation sites hinder a precise understanding of its functional impacts. Clarifying these aspects is expected to emerge as a major focus in glycomics and antibody engineering research.<\/jats:p>","DOI":"10.3390\/biom15111508","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T02:50:48Z","timestamp":1761533448000},"page":"1508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fab N-Glycosylation in IgG: Implications in Physiological and Pathological Immune Regulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Shuqi","family":"Chen","sequence":"first","affiliation":[{"name":"International Science and Technology Cooperation Base for Molecular Medicine, Department of Pathology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5421-3023","authenticated-orcid":false,"given":"Feiyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binliang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9678-0706","authenticated-orcid":false,"given":"Ganbo","family":"Liang","sequence":"additional","affiliation":[{"name":"Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyi","family":"Xu","sequence":"additional","affiliation":[{"name":"International Science and Technology Cooperation Base for Molecular Medicine, Department of Pathology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-2406","authenticated-orcid":false,"given":"Qian","family":"Xu","sequence":"additional","affiliation":[{"name":"International Science and Technology Cooperation Base for Molecular Medicine, Department of Pathology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vidarsson, G., Dekkers, G., and Rispens, T. (2014). IgG subclasses and allotypes: From structure to effector functions. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00520"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1146\/annurev.bi.48.070179.004525","article-title":"Three-dimensional structure of immunoglobulins","volume":"48","author":"Amzel","year":"1979","journal-title":"Annu. Rev. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/264415a0","article-title":"Crystallographic structure studies of an IgG molecule and an Fc fragment","volume":"264","author":"Huber","year":"1976","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dekkers, G., Rispens, T., and Vidarsson, G. (2018). Novel Concepts of Altered Immunoglobulin G Galactosylation in Autoimmune Diseases. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00553"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6632","DOI":"10.1073\/pnas.80.21.6632","article-title":"Biological significance of carbohydrate chains on monoclonal antibodies","volume":"80","author":"Nose","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0161-5890(00)00105-X","article-title":"The influence of glycosylation on the thermal stability and effector function expression of human IgG1-Fc: Properties of a series of truncated glycoforms","volume":"37","author":"Mimura","year":"2000","journal-title":"Mol. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26733","DOI":"10.1074\/jbc.M202069200","article-title":"Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity","volume":"277","author":"Shields","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1172\/JCI130029","article-title":"Functional diversification of IgGs through Fc glycosylation","volume":"129","author":"Wang","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/bj2590347","article-title":"Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing Fc gamma RI and\/or Fc gamma RII receptors","volume":"259","author":"Walker","year":"1989","journal-title":"Biochem. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/0161-5890(95)00118-2","article-title":"The effect of the removal of sialic acid, galactose and total carbohydrate on the functional activity of Campath-1H","volume":"32","author":"Boyd","year":"1995","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1021\/bp050228w","article-title":"Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro","volume":"21","author":"Hodoniczky","year":"2005","journal-title":"Biotechnol. Prog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7405","DOI":"10.1074\/jbc.M602690200","article-title":"Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor","volume":"282","author":"Radcliffe","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1128\/IAI.73.4.2554-2555.2005","article-title":"The mannose receptor mediates the cellular immune response in human coccidioidomycosis","volume":"73","author":"Ampel","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5430","DOI":"10.7150\/thno.53961","article-title":"Sialylated immunoglobulin G: A promising diagnostic and therapeutic strategy for autoimmune diseases","volume":"11","author":"Li","year":"2021","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1074\/mcp.M116.062919","article-title":"Structural Analysis of Variable Domain Glycosylation of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis Reveals the Presence of Highly Sialylated Glycans","volume":"16","author":"Hafkenscheid","year":"2017","journal-title":"Mol. Cell. Proteom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1081\/IMM-120004802","article-title":"Occurrence, properties, and function of asymmetric IgG molecules isolated from non-immune sera","volume":"31","author":"Canellada","year":"2002","journal-title":"Immunol. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1074\/mcp.M114.039537","article-title":"Immunoglobulin G (IgG) Fab Glycosylation Analysis Using a New Mass Spectrometric High-throughput Profiling Method Reveals Pregnancy-associated Changes","volume":"13","author":"Bondt","year":"2014","journal-title":"Mol. Cell. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jim.2012.05.022","article-title":"Quantitative glycan profiling of normal human plasma derived immunoglobulin and its fragments Fab and Fc","volume":"382","author":"Anumula","year":"2012","journal-title":"J. Immunol. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/0161-5890(86)90026-X","article-title":"The asymmetric IgG non-precipitating antibody. Localization of the oligosaccharide involved, by concanavalin A interaction","volume":"23","author":"Leoni","year":"1986","journal-title":"Mol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1021\/bp040016j","article-title":"Glycosylation of recombinant antibody therapeutics","volume":"21","author":"Jefferis","year":"2005","journal-title":"Biotechnol. Prog."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.bbagen.2005.11.021","article-title":"Differential glycosylation of polyclonal IgG, IgG-Fc and IgG-Fab isolated from the sera of patients with ANCA-associated systemic vasculitis","volume":"1760","author":"Holland","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1073\/pnas.1711720115","article-title":"Adaptive antibody diversification through N-linked glycosylation of the immunoglobulin variable region","volume":"115","author":"Derksen","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.4049\/jimmunol.162.4.2162","article-title":"Position effects of variable region carbohydrate on the affinity and in vivo behavior of an anti-(1-->6) dextran antibody","volume":"162","author":"Coloma","year":"1999","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"van de Bovenkamp, F.S., Derksen, N.I.L., van Breemen, M.J., de Taeye, S.W., Ooijevaar-de Heer, P., Sanders, R.W., and Rispens, T. (2018). Variable Domain N-linked glycans acquired During antigen-specific immune responses can contribute to immunoglobulin G antibody stability. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00740"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1002\/j.1460-2075.1991.tb07819.x","article-title":"Antibody variable region glycosylation: Position effects on antigen binding and carbohydrate structure","volume":"10","author":"Wright","year":"1991","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1182\/blood-2014-11-609404","article-title":"Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma","volume":"125","author":"Schneider","year":"2015","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000087964","article-title":"Asymmetric antibodies: A protective arm in pregnancy","volume":"89","author":"Gutierrez","year":"2005","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cell.2020.03.007","article-title":"Challenges, Progress, and Prospects of Developing Therapies to Treat Autoimmune Diseases","volume":"181","author":"Fugger","year":"2020","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"514","DOI":"10.4049\/jimmunol.1302644","article-title":"Ig gene analysis reveals altered selective pressures on Ig-producing cells in parotid glands of primary Sjogren\u2019s syndrome patients","volume":"194","author":"Hamza","year":"2015","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1016\/j.jaci.2022.10.035","article-title":"Differences in IgG autoantibody Fab glycosylation across autoimmune diseases","volume":"151","author":"Koers","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lardinois, O.M., Deterding, L.J., Hess, J.J., Poulton, C.J., Henderson, C.D., Jennette, J.C., Nachman, P.H., and Falk, R.J. (2019). Immunoglobulins G from patients with ANCA-associated vasculitis are atypically glycosylated in both the Fc and Fab regions and the relation to disease activity. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213215"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vletter, E.M., Koning, M.T., Scherer, H.U., Veelken, H., and Toes, R.E.M. (2020). A Comparison of Immunoglobulin Variable Region N-Linked Glycosylation in Healthy Donors, Autoimmune Disease and Lymphoma. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00241"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/annrheumdis-2014-206598","article-title":"Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis","volume":"75","author":"Rombouts","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/eji.201747446","article-title":"Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: Implications for B-cell selection","volume":"48","author":"Lloyd","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1136\/annrheumdis-2017-212052","article-title":"B-cell receptor sequencing of anti-citrullinated protein antibody (ACPA) IgG-expressing B cells indicates a selective advantage for the introduction of N-glycosylation sites during somatic hypermutation","volume":"77","author":"Vergroesen","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/0161-5890(95)00078-S","article-title":"Glycosylation of the variable region of immunoglobulin G--site specific maturation of the sugar chains","volume":"32","author":"Endo","year":"1995","journal-title":"Mol. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/art.40920","article-title":"N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis","volume":"71","author":"Hafkenscheid","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.4049\/jimmunol.2100225","article-title":"Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes","volume":"207","author":"Fichtner","year":"2021","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1111\/jgh.14512","article-title":"Unique patterns of glycosylation in immunoglobulin subclass G4-related disease and primary sclerosing cholangitis","volume":"34","author":"Culver","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18587","DOI":"10.1073\/pnas.1009388107","article-title":"Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins","volume":"107","author":"Coelho","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.amjmed.2005.03.037","article-title":"Male microchimerism in women without sons: Quantitative assessment and correlation with pregnancy history","volume":"118","author":"Yan","year":"2005","journal-title":"Am. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1634\/stemcells.2004-0169","article-title":"Fetal microchimerism in the maternal mouse brain: A novel population of fetal progenitor or stem cells able to cross the blood-brain barrier?","volume":"23","author":"Tan","year":"2005","journal-title":"Stem Cells"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, X., and Wei, H. (2021). Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.728291"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1034\/j.1600-0897.2002.01131.x","article-title":"Dominant IL-10 and TGF-beta mRNA expression in gammadeltaT cells of human early pregnancy decidua suggests immunoregulatory potential","volume":"48","author":"Nagaeva","year":"2002","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ni1037","article-title":"Regulatory T cells mediate maternal tolerance to the fetus","volume":"5","author":"Aluvihare","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1600-0897.1999.tb00468.x","article-title":"Progesterone-induced blocking factor inhibits degranulation of natural killer cells","volume":"42","author":"Faust","year":"1999","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/978-1-60761-869-0_25","article-title":"Pregnancy: Tolerance and suppression of immune responses","volume":"677","author":"Leber","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/08830185.2019.1674299","article-title":"Reproductive immunomodulatory functions of B cells in pregnancy","volume":"39","author":"Dutta","year":"2020","journal-title":"Int. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.8755-8920.2001.450504.x","article-title":"Asymmetric antibodies and pregnancy","volume":"45","author":"Zenclussen","year":"2001","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0165-0378(91)90029-P","article-title":"IgG asymmetric molecules with antipaternal activity isolated from sera and placenta of pregnant human","volume":"20","author":"Gentile","year":"1991","journal-title":"J. Reprod. Immunol."},{"key":"ref_51","first-page":"681","article-title":"Immunobiological behaviour of rabbit precipitating and non-precipitating (co-precipitating) antibodies","volume":"41","author":"Margni","year":"1980","journal-title":"Immunology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1136\/annrheumdis-2021-eular.1727","article-title":"AB0020\u2005ACPA ILLUSTRATING THE IMPACT OF IGG FAB-GLYCOSYLATION ON TRANSPLACENTAL TRANSFER OF ANTIBODIES AND THEIR BINDING TO THE NEONATAL FC-RECEPTOR (FCRN)","volume":"80","author":"Volkov","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1034\/j.1600-0897.2002.01141.x","article-title":"In vitro modulation of protective antibody responses by estrogen, progesterone and interleukin-6","volume":"48","author":"Canellada","year":"2002","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1034\/j.1600-0897.2002.01125.x","article-title":"Interleukin regulation of asymmetric antibody synthesized by isolated placental B cells","volume":"48","author":"Canellada","year":"2002","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jri.2008.11.002","article-title":"Low levels of serum asymmetric antibodies as a marker of threatened pregnancy","volume":"79","author":"Barrientos","year":"2009","journal-title":"J. Reprod. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.imlet.2005.11.006","article-title":"Differential macrophage modulation of asymmetric IgG antibody synthesis by soluble or particulate stimuli","volume":"103","author":"Apicella","year":"2006","journal-title":"Immunol. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1093\/humrep\/deu323","article-title":"Fab fragment glycosylated IgG may play a central role in placental immune evasion","volume":"30","author":"Gu","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Li, J., Korteweg, C., Qiu, Y., Luo, J., Chen, Z., Huang, G., Li, W., and Gu, J. (2014). Two ultrastructural distribution patterns of immunoglobulin G in human placenta and functional implications. Biol. Reprod., 91.","DOI":"10.1095\/biolreprod.114.122614"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0165-0378(92)90014-U","article-title":"Preferential synthesis of asymmetric antibodies in rats immunized with paternal particulate antigens. Effect on pregnancy","volume":"22","author":"Gentile","year":"1992","journal-title":"J. Reprod. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/ni1102-991","article-title":"Cancer immunoediting: From immunosurveillance to tumor escape","volume":"3","author":"Dunn","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1158\/1078-0432.CCR-21-1804","article-title":"Cancer Immunoediting in the Era of Immuno-oncology","volume":"28","author":"Gubin","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1365-2141.1994.tb04780.x","article-title":"Clonal history of a human follicular lymphoma as revealed in the immunoglobulin variable region genes","volume":"86","author":"Zhu","year":"1994","journal-title":"Br. J. Haematol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.imlet.2020.11.003","article-title":"Progress in research into the role of abnormal glycosylation modification in tumor immunity","volume":"229","author":"Liu","year":"2021","journal-title":"Immunol. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/j.bbagen.2016.01.011","article-title":"IgG and IgM glycosylation patterns in patients undergoing image-guided tumor ablation","volume":"1860","author":"Breen","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1182\/blood-2015-04-640912","article-title":"DC-SIGN-expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma","volume":"126","author":"Amin","year":"2015","journal-title":"Blood"},{"key":"ref_66","first-page":"143","article-title":"An increased level of the Concanavalin A-positive IgG in the serum of patients with gastric cancer as evaluated by a lectin enzyme-linked immunosorbent assay (LELISA)","volume":"55","author":"Klaamas","year":"2008","journal-title":"Neoplasma"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Li, S., Meng, J., Xu, F., Wang, Q., Tian, X., Li, M., Zeng, X., Hu, C., and Zheng, Y. (2022). IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray. J. Clin. Med., 11.","DOI":"10.3390\/jcm11195727"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1002\/pmic.200800931","article-title":"A close look at human IgG sialylation and subclass distribution after lectin fractionation","volume":"9","author":"Stadlmann","year":"2009","journal-title":"Proteomics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"31166","DOI":"10.18632\/oncotarget.9085","article-title":"Fractionation of Fab glycosylated immunoglobulin G with concanavalin A chromatography unveils new structural properties of the molecule","volume":"7","author":"Huang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1007\/s00262-020-02809-z","article-title":"A study of the possible role of Fab-glycosylated IgG in tumor immunity","volume":"70","author":"Xu","year":"2021","journal-title":"Cancer Immunol. Immunother. CII"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1158\/0008-5472.CAN-22-2733","article-title":"A Self-Propagating c-Met-SOX2 Axis Drives Cancer-Derived IgG Signaling That Promotes Lung Cancer Cell Stemness","volume":"83","author":"Huang","year":"2023","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/jb\/mvaa116","article-title":"Glycosylation decreases aggregation and immunogenicity of adalimumab Fab secreted from Pichia pastoris","volume":"169","author":"Nakamura","year":"2021","journal-title":"J. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.bbrc.2018.06.071","article-title":"Introduction of a glycosylation site in the constant region decreases the aggregation of adalimumab Fab","volume":"503","author":"Nakamura","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5431","DOI":"10.1021\/acs.analchem.0c00185","article-title":"Comparative Elucidation of Cetuximab Heterogeneity on the Intact Protein Level by Cation Exchange Chromatography and Capillary Electrophoresis Coupled to Mass Spectrometry","volume":"92","author":"Fussl","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ab.2007.01.023","article-title":"Structural characterization of N-linked oligosaccharides on monoclonal antibody cetuximab by the combination of orthogonal matrix-assisted laser desorption\/ionization hybrid quadrupole-quadrupole time-of-flight tandem mass spectrometry and sequential enzymatic digestion","volume":"364","author":"Qian","year":"2007","journal-title":"Anal. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/978-1-62703-327-5_7","article-title":"Cetuximab Fab and Fc N-glycan fast characterization using IdeS digestion and liquid chromatography coupled to electrospray ionization mass spectrometry","volume":"988","author":"Tonini","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"12023","DOI":"10.1073\/pnas.1812833115","article-title":"Site-selective chemoenzymatic glycoengineering of Fab and Fc glycans of a therapeutic antibody","volume":"115","author":"Giddens","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","first-page":"100","article-title":"Serum IgG subclasses in normal adults","volume":"19","author":"French","year":"1986","journal-title":"Monogr. Allergy"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/10408368909106589","article-title":"Human immunoglobulin G and immunoglobulin G subclasses: Biochemical, genetic, and clinical aspects","volume":"27","author":"Papadea","year":"1989","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11882-015-0580-7","article-title":"IgG4 Characteristics and Functions in Cancer Immunity","volume":"16","author":"Crescioli","year":"2016","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/pro.5560060217","article-title":"Intrachain disulfide bond in the core hinge region of human IgG4","volume":"6","author":"Bloom","year":"1997","journal-title":"Protein Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1126\/science.1144603","article-title":"Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange","volume":"317","author":"Schuurman","year":"2007","journal-title":"Science"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molimm.2012.10.029","article-title":"Crystal structure of the human IgG4 C(H)3 dimer reveals the role of Arg409 in the mechanism of Fab-arm exchange","volume":"54","author":"Davies","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6098","DOI":"10.1074\/jbc.M113.541813","article-title":"Dynamics of inter-heavy chain interactions in human immunoglobulin G (IgG) subclasses studied by kinetic Fab arm exchange","volume":"289","author":"Rispens","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sakthiswary, R., Shaharir, S.S., and Wahab, A.A. (2022). Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030558"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/ar4122","article-title":"IgG4-related disease: Why high IgG4 and fibrosis?","volume":"15","author":"Koike","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1111\/j.1365-2133.2012.11144.x","article-title":"Enrichment of total serum IgG4 in patients with pemphigus","volume":"167","author":"Funakoshi","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00428-016-1914-0","article-title":"A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis","volume":"468","author":"Miyatani","year":"2016","journal-title":"Virchows Arch."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1172\/JCI65579","article-title":"IgG4 subclass antibodies impair antitumor immunity in melanoma","volume":"123","author":"Karagiannis","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1880687","DOI":"10.1080\/2162402X.2021.1880687","article-title":"IgG4 induces tolerogenic M2-like macrophages and correlates with disease progression in colon cancer","volume":"10","author":"Jordakieva","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/hep.25627","article-title":"Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: Molecular mechanism of IgG4 reaction in cancer tissue","volume":"56","author":"Harada","year":"2012","journal-title":"Hepatology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e000661","DOI":"10.1136\/jitc-2020-000661","article-title":"An immune evasion mechanism with IgG4 playing an essential role in cancer and implication for immunotherapy","volume":"8","author":"Wang","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/icb.2014.44","article-title":"Human immunoglobulin classes and subclasses show variability in VDJ gene mutation levels","volume":"92","author":"Jackson","year":"2014","journal-title":"Immunol. Cell Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"8344","DOI":"10.1158\/0008-5472.CAN-06-3304","article-title":"Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer","volume":"67","author":"Hinz","year":"2007","journal-title":"Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/all.13635","article-title":"IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: Potential implication in immune tolerance","volume":"74","author":"Bianchini","year":"2019","journal-title":"Allergy"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1182\/blood-2008-09-179754","article-title":"Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses","volume":"113","author":"Bruhns","year":"2009","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e51444","DOI":"10.15252\/embr.202051444","article-title":"N-glycosylation of PD-1 promotes binding of camrelizumab","volume":"21","author":"Liu","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1158\/2326-6066.CIR-14-0040","article-title":"In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates","volume":"2","author":"Wang","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/S1470-2045(17)30421-7","article-title":"Nivolumab versus standard, single-agent therapy of investigator\u2019s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): Health-related quality-of-life results from a randomised, phase 3 trial","volume":"18","author":"Harrington","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/S1470-2045(18)30351-6","article-title":"Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial","volume":"19","author":"Zhu","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S1470-2045(17)30380-7","article-title":"Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: A secondary analysis of the KEYNOTE-001 phase 1 trial","volume":"18","author":"Shaverdian","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Zhang, W., Quan, Y., Ma, X., Zeng, L., Li, J., Chen, S., Su, M., Hong, L., Li, P., and Wang, H. (2023). Synergistic effect of glutathione and IgG4 in immune evasion and the implication for cancer immunotherapy. Redox Biol., 60.","DOI":"10.1016\/j.redox.2023.102608"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.4049\/jimmunol.1801622","article-title":"Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation","volume":"202","author":"Koers","year":"2019","journal-title":"J. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Koning, M.T., Trollmann, I.J.M., van Bergen, C.A.M., Alvarez Saravia, D., Navarrete, M.A., Kielbasa, S.M., and Veelken, H. (2019). Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01543"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.jaci.2016.06.040","article-title":"Antibody-encoding repertoires of bone marrow and peripheral blood-a focus on IgE","volume":"139","author":"Levin","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.4049\/jimmunol.1502136","article-title":"The Emerging Importance of IgG Fab Glycosylation in Immunity","volume":"196","author":"Hafkenscheid","year":"2016","journal-title":"J. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.molimm.2012.06.012","article-title":"Fc-Fc interactions of human IgG4 require dissociation of heavy chains and are formed predominantly by the intra-chain hinge isomer","volume":"53","author":"Rispens","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.2217\/fon.15.52","article-title":"Nivolumab: Targeting PD-1 to bolster antitumor immunity","volume":"11","author":"Brahmer","year":"2015","journal-title":"Future Oncol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:11:15Z","timestamp":1761628275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":108,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["biom15111508"],"URL":"https:\/\/doi.org\/10.3390\/biom15111508","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]}}}