Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA)

Abstract

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.

Differences between intravenous iron products: focus on treatment of iron deficiency in chronic heart failure patients

“…iron products have been conducted in CHF patients, and thus, data on differences in efficacy and safety are limited. 54,55 Hypersensitivity reactions and anaphylactic reactions occurred most frequently with iron dextrans. 22,[45][46][47][48][49][50][51][52] However, because most of these studies were conducted with different iron doses, efficacy data cannot be compared.…”

“…iron complexes carry a potential risk for dextraninduced anaphylactic reactions. 54,55 Hypersensitivity reactions and anaphylactic reactions occurred most frequently with iron dextrans. 56,57 In particular, high-molecular-weight iron dextran is associated with higher HSR rates and more severe reactions, including death.…”

Glycopolymers from Saccharomyces Cerevisiae BIM Y-195 with Unusual Immunochemical Properties: Isolation, Structural Identification and Prediction of Their Role in Pathogenesis/Treatment of Autoimmune Thyroid Diseases

“…Recently it was shown that S. cerevisiae NRRL Y-1534 produce secretory dextran with average molecular weight 67 kDa (Moussa and Khalil, 2012). The data on numerous applications of the dextrans and derivative substances in food industry and clinical practice suggest that the negative effects of dextrans on human health were not found to date (Liu et al, 2009;Neiser et al, 2011;Qader et al, 2005).…”

“…It has been shown that dextran-specific antibodies (anti-dextrans) commonly detected in the serum samples of healthy donors are produced as result of immune response to naturally occurring dextrans from caries-inducing Streptococcus species and intestinal bacteria (Neiser et al, 2011;Paul et al, 2009). Antigenic determinants of α-1, 6-glucans responsible for its specific interaction with human anti-dextrans involve six and perhaps seven glucosyl residues (Cisar et al, 1975).…”

“…We assume that 5 -7 kDa α-1, 6-glucan from S. cerevisiae BIM Y-195 has low immunogenicity, since it was shown that low molecular weight dextrans are appreciably less immunogenic than high molecular weight dextrans (Neiser et al, 2011). However, we can not exclude the presence of immunologically relevant BPs with the same structure but higher molecular weight in the cells of the yeast, which allow us to include antibodies to α-1, 6-glucan from S. cerevisiae Firstly, we assume that α-1, 6-glucan is able to bind pre-existing serum anti-TPO (antiTg) (Figure 9, 1).…”