Comparison of Fc N-Glycosylation of Pharmaceutical Products of Intravenous Immunoglobulin G.

Willem Jan R Fokkink,Manfred Wuhrer,Tom C M Santbergen,Ruth Huizinga,Bart C Jacobs,David Falck

doi:10.1371/journal.pone.0139828

Willem Jan R Fokkink, Manfred Wuhrer + Show 4 more

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https://doi.org/10.1371/journal.pone.0139828

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Abstract

Intravenous immunoglobulin (IVIg) products from different pharmaceutical companies vary in composition, in part because of the selected blood donors and production process. N-glycosylation of the Fc-portion of IgG varies between blood donors and may influence both the side-effects and therapeutic effectiveness of IVIg. At present, the variation in Fc N-glycosylation between IVIg products has not been defined. Utilizing mass spectrometry, we performed relative quantitation of the Fc N-glycosylation of IgG, assessing a total of 154 unique lot numbers of IVIg. Seven products showed comparable Fc N-glycosylation, with only one product differing from the others in all glycosylation features (galactosylation, sialylation, fucosylation and bisecting N-acetylglucosamine). However, the mean difference did not exceed 3%. Within product variation was present to a minor degree, but largely indistinguishable from analytical variation. In conclusion, we expect that the minor variation in Fc N-glycosylation between IVIg products has a small effect, if any, on the biological activity.

Highlights

Intravenous immunoglobulin (IVIg) is the mainstay treatment for a broad spectrum of immune deficiencies and autoimmune diseases
The normalized relative intensities of the IgG1 Fc N-galactosylation. sialylation, fucosylation and bisecting N-acetylglucosamine (GlcNAc) for all analyzed IVIg products and controls are presented in Table 1 and Fig 1
This study showed that the seven IVIg products commonly used for treatment of patients in The Netherlands have a similar IgG Fc N-glycosylation

Summary

Introduction

Intravenous immunoglobulin (IVIg) is the mainstay treatment for a broad spectrum of immune deficiencies and autoimmune diseases. In addition to the FDA approved indications, IVIg is frequently used off-label for other (immune) disorders [1,2]. For years the world consumption and costs of IVIg has been increasing, creating a billion dollar global market [3,4]. A select number of pharmaceutical companies (and local blood banks) market IVIg, and these products differ with respect to the blood donor pool and production methods, leading to variation in the product composition (e.g. IgG subclass distribution, stabilizers, sodium, IgA) [5,6,7,8]. Only a few studies have compared the clinical efficacy of different IVIg products used for high-dose immune-modulatory treatment [9].

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