Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA)
Open accessAbstract
Intravenous iron preparations are typically classified as non-dextran-based or dextran/dextran-based complexes. The carbohydrate shell for each of these preparations is unique and is key in determining the various physicochemical properties, the metabolic pathway, and the immunogenicity of the iron-carbohydrate complex. As intravenous dextran can cause severe, antibody-mediated dextran-induced anaphylactic reactions (DIAR), the purpose of this study was to explore the potential of various intravenous iron preparations, non-dextran-based or dextran/dextran-based, to induce these reactions. An IgG-isotype mouse monoclonal anti-dextran antibody (5E7H3) and an enzyme-linked immunosorbent assay (ELISA) were developed to investigate the dextran antigenicity of low molecular weight iron dextran, ferumoxytol, iron isomaltoside 1000, ferric gluconate, iron sucrose and ferric carboxymaltose, as well as isomaltoside 1000, the isolated carbohydrate component of iron isomaltoside 1000. Low molecular weight iron dextran, as well as dextran-based ferumoxytol and iron isomaltoside 1000, reacted with 5E7H3, whereas ferric carboxymaltose, iron sucrose, sodium ferric gluconate, and isolated isomaltoside 1000 did not. Consistent results were obtained with reverse single radial immunodiffusion assay. The results strongly support the hypothesis that, while the carbohydrate alone (isomaltoside 1000) does not form immune complexes with anti-dextran antibodies, iron isomaltoside 1000 complex reacts with anti-dextran antibodies by forming multivalent immune complexes. Moreover, non-dextran based preparations, such as iron sucrose and ferric carboxymaltose, do not react with anti-dextran antibodies. This assay allows to assess the theoretical possibility of a substance to induce antibody-mediated DIARs. Nevertheless, as this is only one possible mechanism that may cause a hypersensitivity reaction, a broader set of assays will be required to get an understanding of the mechanisms that may lead to intravenous iron-induced hypersensitivity reactions.
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Cites
Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122 · see citing works
The Influence of Antigen Organization on B Cell Responsiveness
Bachmann, M. F., Rohrer, U. H., Kündig, T. M., Bürki, K., Hengartner, H., & Zinkernagel, R. M. (1993) · Science · doi:10.1126/science.8248784 · Cited by 718 · see citing works
Update on adverse drug events associated with parenteral iron
Chertow, G. M., Mason, P. D., Vaage-Nilsen, O., & Ahlmén, J. (2005) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfi253 · Cited by 457 · see citing works
FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease
Lu, M., Cohen, M. H., Rieves, D., & Pazdur, R. (2010) · American Journal of Hematology · doi:10.1002/ajh.21656 · Cited by 443 · see citing works
Koskenkorva-Frank, T. S., Weiss, G., Koppenol, W. H., & Burckhardt, S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.001 · Cited by 406 · see citing works
Self-citationFerumoxytol for Treating Iron Deficiency Anemia in CKD
Spinowitz, B., Kausz, A. T., Baptista, J., Noble, S., Sothinathan, R., Bernardo, M. V., Brenner, L., & Pereira, B. J. G. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007101156 · Cited by 261 · see citing works
Jahn, M. R., Andreasen, H. B., Fütterer, S., Nawroth, T., Schünemann, V., Kolb, U., Hofmeister, W., Muñoz, M., Bock, K., Meldal, M., et al. (2011) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2011.03.016 · Cited by 256 · see citing works
Comparative risk of anaphylactic reactions associated With intravenous iron products
Wang, C., Graham, D. J., Kane, R. C., Xie, D., Wernecke, M., Levenson, M., MaCurdy, T. E., Houstoun, M., Ryan, Q., Wong, S., et al. (2015) · JAMA · doi:10.1001/jama.2015.15572 · Cited by 219 · see citing works
The influence of virus structure on antibody responses and virus serotype formation
Bachmann, M. F., & Zinkernagel, R. M. (1996) · Immunology Today · doi:10.1016/s0167-5699(96)10066-9 · Cited by 205 · see citing works
Ferumoxytol as an Intravenous Iron Replacement Therapy in Hemodialysis Patients
Provenzano, R., Schiller, B. M., Rao, M., Coyne, D. W., Brenner, L., & Pereira, B. J. G. (2009) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.02840608 · Cited by 187 · see citing works
Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management
Szebeni, J., Fishbane, S. N., Hedenus, M., Howaldt, S. M., Locatelli, F., Patni, S., Rampton, D. S., Weiss, G., & Folkersen, J. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13268 · Cited by 162 · see citing works
The Upper Limit for the Size of the Human Antidextran Combining Site
Kabat, E. A. (1960) · The Journal of Immunology · doi:10.4049/jimmunol.84.1.82 · Cited by 156 · see citing works
Safety of Ferumoxytol in Patients With Anemia and CKD
Singh, A. K., Patel, T. V., Hertel, J., Bernardo, M. V., Kausz, A., & Brenner, L. (2008) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2008.08.001 · Cited by 146 · see citing works
Safety of intravenous iron formulations: facts and folklore.
Auerbach, M., & Macdougall, I. C. (2014) · PubMed Central · doi:10.2450/2014.0094-14 · Cited by 109 · see citing works
SIMON, G. H., von Vopelius‐Feldt, J., Fu, Y., Schlegel, J., Pinotek, G., Wendland, M. F., Chen, M., & Daldrup-Link, H. E. (2005) · Investigative Radiology · doi:10.1097/01.rli.0000191367.61306.83 · Cited by 108 · see citing works
Neiser, S., Rentsch, D., Dippon, U., Kappler, A. A., Weidler, P. G., Göttlicher, J., Steininger, R., Wilhelm, M., Braitsch, M., Funk, F., et al. (2015) · BioMetals · doi:10.1007/s10534-015-9845-9 · Cited by 89 · see citing works
Self-citationKudasheva, D. S., Lai, J., Ulman, A., & Cowman, M. K. (2004) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2004.06.010 · Cited by 84 · see citing works
Kraft, D., Hédin, H., Richter, W., Scheiner, O., Rumpold, H., & Devey, M. E. (1982) · Allergy · doi:10.1111/j.1398-9995.1982.tb02331.x · Cited by 82 · see citing works
Regulatory Challenges and Approaches to Characterize Nanomedicines and their Follow-On Similars
Mühlebach, S., Borchard, G., & Yildiz, S. (2015) · Nanomedicine · doi:10.2217/nnm.14.189 · Cited by 76 · see citing works
Predictive capacity of histamine release for the diagnosis of drug allergy
Demoly, P. M., Lebel, B., Messaad, D., Sahla, H., Rongier, M., Daurès, J., Godard, P., & Bousquet, J. (1999) · Allergy · doi:10.1034/j.1398-9995.1999.00020.x · Cited by 73 · see citing works
Immunologic studies of anaphylaxis to iron dextran in patients on renal dialysis.
Novey, H. S., Pahl, M. V., Haydik, I. B., & Vaziri, N. D. (1994) · PubMed · Cited by 68 · see citing works
Fleming, L. W., Stewart, W. K., & Parratt, D. (1992) · Nephrology Dialysis Transplantation · doi:10.1093/oxfordjournals.ndt.a091987 · Cited by 64 · see citing works
Safety of Dextran in Relation to Other Colloids – Ten Years Experience with Hapten Inhibition
Ljungström, K.-G. (2009) · Infusionstherapie und Transfusionsmedizin / Infusion Therapy and Transfusion Medicine · doi:10.1159/000222845 · Cited by 64 · see citing works
Funk, F., Ryle, P. R., Canclini, C., Neiser, S., & Geisser, P. (2011) · Arzneimittelforschung · doi:10.1055/s-0031-1296299 · Cited by 64 · see citing works
Self-citationHigh-Molecular Weight Iron Dextran: A Wolf in Sheep's Clothing?
Rodgers, G. M., Auerbach, M., Cella, D., Chertow, G. M., Coyne, D. W., Glaspy, J. A., & Henry, D. H. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008030255 · Cited by 56 · see citing works
Richter, A. W., & Hédin, H. (1982) · Immunology Today · doi:10.1016/0167-5699(82)90073-1 · Cited by 56 · see citing works
Wíkström, B., Bhandari, S., Barany, P. F., Kalra, P. A., Ladefoged, S. A., Wilske, J., & Thomsen, L. L. (2011) · Journal of Nephrology · doi:10.5301/jn.2011.6248 · Cited by 53 · see citing works
Essential but toxic: Controlling the flux of iron in the body
Anderson, G. J., & Wang, F. (2011) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2011.05661.x · Cited by 49 · see citing works
Pai, A. B., & Garba (2012) · Journal of Blood Medicine · doi:10.2147/jbm.s29204 · Cited by 47 · see citing works
Hildebrandt, P. R., Bruun, N. E., Nielsen, O. W., Pantev, E., SHIVA, F., Videbæk, L. M., Wikström, G., & Thomsen, L. L. (2010) · Transfusion Alternatives in Transfusion Medicine · doi:10.1111/j.1778-428x.2010.01145.x · Cited by 33 · see citing works
Anaphylaxis with elevated serum tryptase after administration of intravenous ferumoxytol
Santosh, S., Podaralla, P., & Miller, B. W. (2010) · Clinical Kidney Journal · doi:10.1093/ndtplus/sfq084 · Cited by 29 · see citing works
Pharmacokinetics of iron isomaltoside 1000 in patients with inflammatory bowel disease
Thomsen, L. L., Nordfjeld, K., & Andreasen, H. B. (2012) · Drug Design Development and Therapy · doi:10.2147/dddt.s30015 · Cited by 29 · see citing works
Assessment of dextran antigenicity of intravenous iron products by an immunodiffusion assay
Neiser, S., Wilhelm, M., Schwarz, K., Funk, F., Geisser, P., & Burckhardt, S. (2011) · Cited by 24 · see citing works
Self-citationAnaphylactic Reaction to Dextran
GETZEN, J. H. (1963) · Archives of Internal Medicine · doi:10.1001/archinte.1963.03860020066006 · Cited by 17 · see citing works
Richter, W. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000231338 · Cited by 9 · see citing works
Dorner, M. M., & Kabat, E. A. (1968) · Immunochemistry · doi:10.1016/0019-2791(68)90184-5 · Cited by 6 · see citing works
Neiser, S., Schwarz, K., Wilhelm, M., Funk, F., Geisser, P., & Burckhardt, S. (2012) · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
3 of the 40 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Ten Things You Might Not Know about Iron Oxide Nanoparticles
Daldrup-Link, H. E. (2017) · Radiology · doi:10.1148/radiol.2017162759 · Cited by 176 · see citing works
Intravenous Irons: From Basic Science to Clinical Practice
Bhandari, S., Pereira, D. I. A., Chappell, H. F., & Drakesmith, H. (2018) · Pharmaceuticals · doi:10.3390/ph11030082 · Cited by 86 · see citing works
Risks for Anaphylaxis With Intravenous Iron Formulations
Dave, C. V., Brittenham, G. M., Carson, J. L., & Setoguchi, S. (2022) · Annals of Internal Medicine · doi:10.7326/m21-4009 · Cited by 47 · see citing works
Garbowski, M., Bansal, S. S., Porter, J. B., Mori, C., Burckhardt, S., & Hider, R. C. (2020) · Haematologica · doi:10.3324/haematol.2020.250803 · Cited by 42 · see citing works
Self-citationFunk, F., Flühmann, B., & Barton, A. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042140 · Cited by 43 · see citing works
Martín‐Malo, A., Borchard, G., Flühmann, B., Mori, C., Silverberg, D. S., & Jankowska, E. A. (2019) · ESC Heart Failure · doi:10.1002/ehf2.12400 · Cited by 39 · see citing works
Sindone, A. P., Doehner, W., & Colet, J. C. (2022) · ESC Heart Failure · doi:10.1002/ehf2.14177 · Cited by 30 · see citing works
Hypersensitivity to Intravenous Iron Preparations
Caimmi, S. M. E., Crisafulli, G., Franceschini, F., Liotti, L., Bianchi, A., Bottau, P., Mori, F., Triggiano, P., Paglialunga, C., Saretta, F., et al. (2022) · Children · doi:10.3390/children9101473 · Cited by 26 · see citing works
Intravenous iron: do we adequately understand the short‐ and long‐term risks in clinical practice?
Rund, D. G. (2020) · British Journal of Haematology · doi:10.1111/bjh.17202 · Cited by 25 · see citing works
Zhang, X., Li, M., Lv, Y., Sun, X., Yao, H., Liu, B., Zhao, X., & Huang, X. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.128329 · Cited by 24 · see citing works
Ikuta, K., Shimura, A., Terauchi, M., Yoshii, K., & Kawabata, Y. (2018) · International Journal of Hematology · doi:10.1007/s12185-018-2400-z · Cited by 17 · see citing works
Steveling, E. H., Mateluna, C. M., Meienberg, A., Hartmann, K., Bircher, A. J., & Scherer, K. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.01.009 · Cited by 11 · see citing works
Hsiao, J., Chen, C.-L., Hsieh, W., & Kuo, K. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15061714 · Cited by 9 · see citing works
New Insights of Biomarkers in IgE and Non-IgE-Mediated Drug Hypersensitivity
Mayorga, C., Muñoz‐Cano, R., Rodríguez‐Nogales, A., Fernández‐Santamaría, R., & Fernández, T. D. (2019) · Current Treatment Options in Allergy · doi:10.1007/s40521-019-0201-0 · Cited by 5 · see citing works
Evaluation of the suitability of a Sprague Dawley rat model to assess intravenous iron preparations
Span, K., Pieters, E. H. E., Brinks, V., Hennink, W. E., & Schellekens, H. (2017) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2017.12.001 · Cited by 3 · see citing works
Management of patients with iron deficiency anemia in the context of primary health care. Guidelines
Drapkina, O., Avalueva, E., Bakulin, I., Bakirov, B., Baranov, I., Vinogradova, N., Vinogradova, M. А., Gaponova, T., Gaus, O., Gilyarevsky, S. R., et al. (2025) · Primary Health Care · doi:10.15829/3034-4123-2025-61 · Cited by 1 · see citing works
Erdmann, E., Bauersachs, J. K., Doehner, W., Hasenfuss, G. P., Kindermann, I., Ringwald, G., Rybak, K., Schieffer, B., & Zeiher, A. M. (2018) · MMW - Fortschritte der Medizin · doi:10.1007/s15006-018-0726-3 · Cited by 1 · see citing works
Strom, C. C., & Andreasen, H. B. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010121 · Cited by 1 · see citing works
Burckhardt, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010122
Self-citationKlinische Erkenntnisse zu moderner i.v.-Eisentherapie
Salama-Müller, A., Reuther, S., Meybohm, P., Wiedemann, G. J., & Leschke, M. (2018) · Der Klinikarzt · doi:10.1055/s-0044-101505
Modern Intravenous Iron Therapy: A Review on Safety and Practical Aspects
Juillerat, P., Angelillo‐Scherrer, A., Surbek, D., Restellini, S., Biedermann, L., Rögler, G., Vavricka, Schoepfer, A., Burri, E., Degen, L. P., et al. (2022) · Annals of Hematology & Oncology · doi:10.26420/annhematoloncol.2022.1413
- Authors
- Neiser, S., Koskenkorva, T., Schwarz, K., Wilhelm, M., & Burckhardt, S.
- Affiliations
- Vifor Pharma (Switzerland) (CH)
- Corresponding author
- Burckhardt, Susanna
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2016-07-21
- Volume
- 17
- Issue
- 7
- Pages
- 1185
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC4964554
- OpenAlex
- W2498398935
- Cited by
- 21
- References
- 40
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Vifor Pharma
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Health Sciences › Medicine › Biochemistry › Blood transfusion and management
- Keywords
- intravenous iron, anti-dextran antibodies, ferumoxytol, iron isomaltoside 1000, ferric carboxymaltose, iron sucrose, ferric gluconate, hypersensitivity, immune complexes
- MeSH terms
- Animals, Antibodies, Monoclonal, Dextrans, Enzyme-Linked Immunosorbent Assay, Immunization, Iron, Mice, Inbred BALB C, Mice, Administration, Intravenous
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