Alfred Weber, Austria

Baxalta International, a Takeda company Global Manufacturing Science

Presenter of 1 Presentation

Poster Display Therapy

ANTI-RAGE (RECEPTOR FOR ADVANCED GLYCOSYLATION END PRODUCTS) IGG CONTAINED IN THE INTRAVENOUS (IVIG) IGG PREPRATION KIOVIG ARE MAINLY OF IGG2 SUBCLASS

Lecture Time
10:54 - 10:55
Room
Poster Area
Date
20.09.2019, Friday
Session Time
10:00 - 17:00
Board Number
207
Presentation Topic
Therapy

Abstract

Background and Aims

Intravenous Immunoglobulin (IVIG) has been established for the treatment of various autoimmune and systemic inflammatory conditions. Several modes of action including the modulation Fc receptor function, interference with complement activation and cytokine network, and provision of anti-idiotypic antibodies have been proposed. We show here that anti-RAGE (receptor for advanced glycosylation endproducts) IgGs, contained in the IVIG preparation KIOVIG, are predominantly from the IgG2 subclass.

Methods

A synthetic N-terminal human RAGE peptide was used to set up an ELISA and after immobilization to purify anti-RAGE IgG from KIOVIG. IgG subclasses were measured with ELISAs; α2,6-bound sialic acid levels were determined with a lectin binding assay using Sambucus nigra agglutinin.

Results

Uniform anti-RAGE IgG titer were found in 14 lots of KIOVIG. Affinity purification provided a fraction counting for 0.07% of the loaded IgG with an anti-RAGE IgG concentration 300-times higher than that of the starting material. IgG2 counted for 88% of the total IgG which was more than twice as high as that measured for the starting material. The content of α2,6-bound sialic acid was reduced and made up only 63% of that measured for the starting material.

Conclusions

Naturally occurring anti-RAGE IgGs predominantly belong to the IgG2 subclass. IgG2 antibodies have low affinities to all Fcg-receptors and activate complement less effectively than IgG3 or IgG1. Binding of naturally occurring anti-RAGE IgG to cell surface expressed RAGE could inhibit activating downstream signaling and due to the low effector functions of these IgG2 antibodies not results in destruction of the RAGE-expressing cell.

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