High-resolution physicochemical characterization of different intravenous immunoglobulin products

PLoS One. 2017 Jul 31;12(7):e0181251. doi: 10.1371/journal.pone.0181251. eCollection 2017.

Abstract

Intravenous immunoglobulin (IVIg) is a complex mixture drug comprising diverse immunoglobulins and non-IgG proteins purified from the plasma of thousands of healthy donors. Approved IVIg products on the market differ regarding source of plasma, isolation process, and formulation. These products are used widely, and often interchangeably, for the treatment of immunodeficiency and autoimmune and inflammatory diseases, but their mechanisms of action in different indications are not well understood. A primary limitation to understanding the therapeutic relevance of specific components within IVIg has been the limited resolution of analytics historically implemented to characterize its complex mixture. In this study, high-resolution analytics were applied to better understand the composition of IVIg and product variations. We characterized three approved IVIg products: Gammagard®, Privigen®, and Octagam®. Differences in the distribution of molecular weight species, IgG sequence variants, isoforms, glycoforms, and the repertoire of previously reported antibody specificities were identified. We also compared the effect of aging on these products to identify changes in size distribution and posttranslational modifications. This type of characterization may provide insights into the specific factors and components of IVIg that may influence its activity and ultimately lead to optimization of IVIg products for use in autoimmune diseases.

MeSH terms

  • Aging
  • Autoimmune Diseases / immunology*
  • Humans
  • Immunoglobulin Fragments / chemistry
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / therapeutic use*
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Deficiency Syndromes / drug therapy*
  • Mass Spectrometry

Substances

  • Immunoglobulin Fragments
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Octagam

Grant support

Momenta Pharmaceuticals Inc. funded the study. The funder provided support in the form of salaries for authors NW, RM, MH, NB, HS, BK, JS, AM, JL, and CJB but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘Author Contributions’ section of the online submission. Momenta Pharmaceuticals Inc. provided funding for medical writing and editorial support.