The biological activity of human monoclonal IgG anti-D is reduced by β-galactosidase treatment
Abstract
The contribution to IgG effector function of exposed galactose residues on the oligosaccharide chains in IgG has been tested experimentally. We studied a human monoclonal antibody (BRAD-5) to the Rh D blood group antigen. The preparation used contained a very low percentage of agalactosyl IgG (3.6% ). After digestion with β-galactosidase there was an increase in terminal GlcN Ac indicating an increase in % agalactosyl IgG to approximately 30%. Comparison was made of the Fc receptor-(FcγR)-mediated functional interactions of the two glycoforms of BRAD-5 in assays which measured the recognition and destruction of sensitised erythrocytes by various effector cells. After β-galactosidase treatment, there was a slight reduction in FcγRI-mediated adherence of erythrocytes to U937 cells and phagocytosis of erythrocytes by monocytes. FcγRII-mediated binding of erythrocytes to K562 cells was also reduced. However there was little difference in adherence of erythrocytes to either Daudi cells (via FcγRII) or NK cells (via FcγRIII). There was a consistent reduction in lysis of erythrocytes mediated through FcγRIII on K cells with the γ-galactosidase treated anti-D. Overall the results showed that reduced levels of galactose on IgG anti-D were associated with reduced biological activity in these assays, but the experiments failed to cast light on the physiological role of the agalactosyl glycoform of IgG.
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Enriching the abundance of mAb N-glycoforms with β1,4-linked galactose can enhance complement-dependent cytotoxicity (CDC).
“Enriching the abundance of mAb N-glycoforms with β1,4-linked galactose (Gal) can also be desirable as it has been shown to enhance complement-dependent cytotoxicity (CDC), another mechanism for the selective depletion of tumour cells by Fc activation of the complement pathway [16–21].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [20]
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Shinkawa, T., Nakamura, K., Yamane, N., Shoji-Hosaka, E., Kanda, Y., Sakurada, M., Uchida, K., Anazawa, H., Satoh, M., Yamasaki, M., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210665200 · Cited by 1,413 · see citing works
Immunoglobulin G glycosylation in aging and diseases
Gudelj, I., Lauc, G., & Pezer, M. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.07.009 · Cited by 405 · see citing works
Niwa, R., Shoji-Hosaka, E., Sakurada, M., Shinkawa, T., Uchida, K., Nakamura, K., Matsushima, K., Ueda, R., Hanai, N., & Shitara, K. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2068 · Cited by 327 · see citing works
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Matsumiya, S., Yamaguchi, Y., Saito, J., Nagano, M., Sasakawa, H., Otaki, S., Satoh, M., Shitara, K., & Kato, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.02.034 · Cited by 278 · see citing works
Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity
Nimmerjahn, F., Anthony, R. M., & Ravetch, J. V. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702936104 · Cited by 253 · see citing works
CCR4 as a novel molecular target for immunotherapy of cancer
Ishida, T., & Ueda, R. (2006) · Cancer Science · doi:10.1111/j.1349-7006.2006.00307.x · Cited by 248 · see citing works
N-glycomic biomarkers of biological aging and longevity: A link with inflammaging
Dall’Olio, F., Vanhooren, V., Chen, C. C., Slagboom, P. E., Wuhrer, M., & Franceschi, C. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.02.002 · Cited by 231 · see citing works
Niwa, R., Hatanaka, S., Shoji-Hosaka, E., Sakurada, M., Kobayashi, Y., Uehara, A., Yokoi, H., Nakamura, K., & Shitara, K. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0850 · Cited by 227 · see citing works
In vitro glycoengineering of IgG1 and its effect on Fc receptor binding and ADCC activity
Thomann, M., Schlothauer, T., Dashivets, T., Malik, S., Avenal, C., Bulau, P., Rüger, P., & Reusch, D. (2015) · PLOS ONE · doi:10.1371/journal.pone.0134949 · Cited by 220 · see citing works
Yamaguchi, Y., Nishimura, M., Nagano, M., Yagi, H., Sasakawa, H., Uchida, K., Shitara, K., & Kato, K. (2005) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2005.10.002 · Cited by 204 · see citing works
Niwa, R., Sakurada, M., Kobayashi, Y., Uehara, A., Matsushima, K., Ueda, R., Nakamura, K., & Shitara, K. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2263 · Cited by 187 · see citing works
Zhou, Q., Shankara, S., Roy, A. J., Qiu, H., Estes, S. D., McVie-Wylie, A. J., Culm-Merdek, K., Park, A., Pan, C. Q., & Edmunds, T. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21598 · Cited by 185 · see citing works
Masuda, K., Kubota, T., Kaneko, E., Iida, S., Wakitani, M., Kobayashi-Natsume, Y., Kubota, A., Shitara, K., & Nakamura, K. (2007) · Molecular Immunology · doi:10.1016/j.molimm.2007.02.005 · Cited by 179 · see citing works
Mori, K., Kuni‐Kamochi, R., Yamane‐Ohnuki, N., Wakitani, M., Yamano, K., Imai, H., Kanda, Y., Niwa, R., Iida, S., Uchida, K., et al. (2004) · Biotechnology and Bioengineering · doi:10.1002/bit.20326 · Cited by 174 · see citing works
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Chung, A. W., Crispin, M., Pritchard, L. K., Robinson, H. R., Górny, M. K., Yu, X., Bailey‐Kellogg, C., Ackerman, M. E., Scanlan, C. N., Zolla‐Pazner, S., et al. (2014) · AIDS · doi:10.1097/qad.0000000000000444 · Cited by 123 · see citing works
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Sonneveld, M. E., Natunen, S., Sainio, S., Koeleman, C. A. M., Holst, S., Dekkers, G., Koelewijn, J. M., Partanen, J., van der Schoot, C. E., Wuhrer, M., et al. (2016) · British Journal of Haematology · doi:10.1111/bjh.14053 · Cited by 102 · see citing works
Analytical comparability study of recombinant monoclonal antibody therapeutics
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Masuda, K., Yamaguchi, Y., Kato, K., Takahashi, N., Shimada, I., & Arata, Y. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01557-x · Cited by 91 · see citing works
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Allhorn, M., Briceño, J. G., Baudino, L., Lood, C., Olsson, M. L., Izui, S., & Collin, M. (2010) · Blood · doi:10.1182/blood-2009-08-239020 · Cited by 71 · see citing works
Natsume, A., Wakitani, M., Yamane‐Ohnuki, N., Shoji-Hosaka, E., Niwa, R., Uchida, K., Satoh, M., & Shitara, K. (2005) · Journal of Immunological Methods · doi:10.1016/j.jim.2005.07.025 · Cited by 65 · see citing works
Nakano, M., Higo, D., Arai, E., Nakagawa, T., Kakehi, K., Taniguchi, N., & Kondo, A. (2008) · Glycobiology · doi:10.1093/glycob/cwn115 · Cited by 62 · see citing works
Capillary electrophoresis for the analysis of glycoprotein pharmaceuticals
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Ho, C.-H., Chien, R., Cheng, P., Liu, J.-H., Liu, C., Su, C.-S., Wu, I., Li, I.-C., Tsai, H., Wu, S., et al. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiu388 · Cited by 47 · see citing works
Blondeel, E. J. M., & Aucoin, M. G. (2018) · Biotechnology Advances · doi:10.1016/j.biotechadv.2018.06.008 · Cited by 46 · see citing works
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Luo, C., Chen, S., Xu, N., Wang, C. C., Sai, W., Zhao, W., Li, Y. C., Hu, X. J., Tian, H., Gao, X. D., et al. (2017) · Scientific Reports · doi:10.1038/srep46347 · Cited by 43 · see citing works
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Donini, R., Haslam, S. M., & Kontoravdi, C. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200840 · Cited by 37 · see citing works
Shoji-Hosaka, E., Kobayashi, Y., Wakitani, M., Uchida, K., Niwa, R., Nakamura, K., & Shitara, K. (2006) · The Journal of Biochemistry · doi:10.1093/jb/mvj207 · Cited by 35 · see citing works
Fukushima, E., Yagi, Y., Yamamoto, S., Nakatani, Y., Kakehi, K., Hayakawa, T., & Suzuki, S. (2012) · Journal of Chromatography A · doi:10.1016/j.chroma.2012.02.052 · Cited by 33 · see citing works
Dall’Olio, F. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_17 · Cited by 32 · see citing works
Liu, H., Nowak, C., Andrien, B. A., Shao, M., Ponniah, G., & Neill, A. (2017) · Biotechnology Progress · doi:10.1002/btpr.2498 · Cited by 31 · see citing works
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Böhm, S., Kao, D., & Nimmerjahn, F. (2014) · Current topics in microbiology and immunology · doi:10.1007/978-3-319-07911-0_18 · Cited by 31 · see citing works
Yagi, Y., Yamamoto, S., Kakehi, K., Hayakawa, T., Ohyama, Y., & Suzuki, S. (2011) · Electrophoresis · doi:10.1002/elps.201100126 · Cited by 29 · see citing works
Koenitzer, J. D., Müller, M. M., Leparc, G., Pauers, M., Bechmann, J., Schulz, P., Schaub, J., Enenkel, B., Hildebrandt, T., Hampel, M., et al. (2015) · Biotechnology Journal · doi:10.1002/biot.201400652 · Cited by 28 · see citing works
Ito, K., Furukawa, J., Yamada, K., Tran, N. L., Shinohara, Y., & Izui, S. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1302488 · Cited by 24 · see citing works
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Yamada, K. D., Ito, K., Furukawa, J., Nakata, J., Alvarez, M., Verbeek, J. S., Shinohara, Y., & Izui, S. (2013) · Journal of Autoimmunity · doi:10.1016/j.jaut.2013.09.001 · Cited by 23 · see citing works
Maki, Y., Matsui, Y., Hayakawa, T., Yamamoto, S., Kinoshita, M., & Suzuki, S. (2017) · Journal of Chromatography A · doi:10.1016/j.chroma.2017.03.019 · Cited by 22 · see citing works
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Wren, L. H., Stratov, I., Kent, S. J., & Parsons, M. S. (2013) · Vaccine · doi:10.1016/j.vaccine.2013.08.035 · Cited by 22 · see citing works
The antibody paradigm: present and future development as a scaffold for biopharmaceutical drugs
Jefferis, R. (2009) · Biotechnology and Genetic Engineering Reviews · doi:10.5661/bger-26-1 · Cited by 20 · see citing works
Zhang, Q., Joubert, M. K., Polozova, A., Guzman, R. D., Lakamsani, K., Kinderman, F. S., Xiang, D., Shami, A. S. E., Miscalichi, N., Flynn, G. C., et al. (2020) · Biotechnology Progress · doi:10.1002/btpr.3045 · Cited by 19 · see citing works
Kumpel, B. M., Saldova, R., Koeleman, C. A. M., Abrahams, J. L., Ederveen, A. L. H., Armour, K. L., Olovnikova, N. I., Vidarsson, G., Kapur, R., Rudd, P. M., et al. (2020) · Scientific Reports · doi:10.1038/s41598-019-57393-9 · Cited by 19 · see citing works
Self-citationPace, D. L., Lewis, N. E., Wu, T. J.-T., Gillespie, R., Dan, L., Velayudhan, J., Rohrbach, A. S., & Connell‐Crowley, L. (2016) · Biotechnology Progress · doi:10.1002/btpr.2300 · Cited by 16 · see citing works
Gstöttner, C., Knaupp, A., Vidarsson, G., Reusch, D., Schlothauer, T., Wuhrer, M., & Domínguez‐Vega, E. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.980291 · Cited by 16 · see citing works
Yamaguchi, Y., Takahashi, N., & Kato, K. (2007) · Elsevier eBooks · doi:10.1016/b978-044451967-2/00072-6 · Cited by 16 · see citing works
Kavur, M. M., Lauc, G., & Pezer, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819475-1.00086-9 · Cited by 15 · see citing works
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Zimmermann, M., Nguyen, M., Schultheiss, C. M., Kolmar, H., & Zimmer, A. (2021) · Biotechnology and Bioengineering · doi:10.1002/bit.27695 · Cited by 12 · see citing works
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Galactosylation of serum IgG and autoantibodies in murine models of autoimmune haemolytic anaemia
Barker, R. N., Young, R. D., Leader, K. A., & Elson, C. J. (1999) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1999.01001.x · Cited by 10 · see citing works
Satoh, M., Shitara, K., & Hanai, N. (2007) · Elsevier eBooks · doi:10.1016/b978-044451967-2/00124-0 · Cited by 10 · see citing works
Bheemareddy, B. R., Pulipeta, M., Iyer, P., & Dirisala, V. R. (2019) · Journal of Carbohydrate Chemistry · doi:10.1080/07328303.2018.1541995 · Cited by 7 · see citing works
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Dall’Olio, F., & Malagolini, N. (2021) · Experientia supplementum · doi:10.1007/978-3-030-76912-3_10 · Cited by 9 · see citing works
Barker, R. N., Leader, K. A., & Elson, C. J. (1999) · Autoimmunity · doi:10.3109/08916939908994053 · Cited by 9 · see citing works
Dissecting the Antibody Constant Region Protective Immune Parameters in HIV Infection
Chung, A. W., & Alter, G. (2014) · Future Virology · doi:10.2217/fvl.14.19 · Cited by 8 · see citing works
Tojo, S., Okazaki, A., Wakitani, M., Shinkawa, T., Uchida, K., & Suzawa, T. (2009) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.32.1604 · Cited by 8 · see citing works
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Kakehi, K., & Suzuki, S. (2007) · Elsevier eBooks · doi:10.1016/b978-044451967-2/00033-7 · Cited by 6 · see citing works
Developing microRNAs as engineering tools to modulate monoclonal antibody galactosylation
Klingler, F., Schlossbauer, P., Naumann, L., Handrick, R., Hesse, F., Neusüß, C., & Otte, K. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28616 · Cited by 5 · see citing works
Molecular Engineering III: Fc Engineering
Peipp, M., Beyer, T. D., Dechant, M., & Valerius, T. (2007) · doi:10.1002/9783527619740.ch8 · Cited by 5 · see citing works
Immunoglobulin G Glycosylation in Diseases
Pezer, M. (2021) · Experientia supplementum · doi:10.1007/978-3-030-76912-3_13 · Cited by 4 · see citing works
Human IgG Glycosylation in Inflammation and Inflammatory Disease
Mimura, Y., & Jefferis, R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819475-1.00047-x · Cited by 3 · see citing works
Leung, S., Gao, K., Wang, G. Y., Cheung, B. K. W., Lee, K.-Y., Zhao, Q., Cheung, W., & Wang, J. (2014) · mAbs · doi:10.4161/19420862.2014.985519 · Cited by 3 · see citing works
Role of Antibody Glycosylation in Health, Disease, and Therapy
Nimmerjahn, F. (2025) · Handbook of experimental pharmacology · doi:10.1007/164_2025_744 · Cited by 2 · see citing works
Molecular and Cellular Pathways Involved in the Anti-inflammatory Activity of IgG
Nimmerjahn, F. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7107-3_5
Future Prospects in Antibody Engineering and Therapy
Sibéril, S., & Teillaud, J. (2004) · Springer eBooks · doi:10.1007/978-1-4419-8877-5_12 · Cited by 2 · see citing works
Human IgG Glycosylation in Inflammation and Inflammatory Disease
Jefferis, R. (2007) · Elsevier eBooks · doi:10.1016/b978-044451967-2/00099-4 · Cited by 1 · see citing works
- Authors
- Kumpel, B. M., Wang, Y., Griffiths, H. L., Hadley, A. G., & Rook, G. A. W.
- Affiliations
- International Blood Group Reference Laboratory, Southmead Road, Bristol
- University College London (GB)
- Corresponding author
- Kumpel, Belinda M.
- ORCID
- Rook, Graham A.W.
- Venue
- Human Antibodies
- Publisher
- SAGE Publications
- Published
- 1995-09-01
- Volume
- 6
- Issue
- 3
- Pages
- 82-88
- ISSN
- 0956-960X (ISSN-L)
- 1875-869X
- 1093-2607
- OpenAlex
- W4294605288
- Cited by
- 68
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Antibodies (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- IgG glycosylation, agalactosyl IgG, anti-D monoclonal antibodies, FcγRI, FcγRII, FcγRIII, erythrophagocytosis, NK cell-mediated lysis
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