In vitro evaluation of the biological activities of IgG in seven Chinese intravenous immunoglobulin preparations

J Pharm Biomed Anal. 2018 Mar 20:151:317-323. doi: 10.1016/j.jpba.2018.01.021. Epub 2018 Jan 16.

Abstract

The IgG activities of antigen recognition, Fc-mediated complement activation and cellular Fcγ-receptors (FcγRs) binding are critical for intravenous immunoglobulin (IVIg) immunotherapy in a variety of immune deficiency diseases. Further, these activities could be influenced by different plasma sources and the IVIg manufacturing processes of different manufacturers. This study evaluated and compared the biological activities of IgG in 7 IVIg preparations produced by different Chinese manufacturers. By using ELISA and two-dimensional immunoblotting, the binding capacity and antibody repertoire of IVIg against typical pathogenic antigens were investigated. Further, Fc-mediated complement activation and receptor binding activities were measured by the haemolysis method and flow-cytometric assay respectively. The results showed that all of the preparations tested have a broad spectrum of antibodies against the E. coli O157:H7 proteome, and each IVIg has its own distinct antibody repertoire. Compared to the European Pharmacopoeia IgG standard, the mean indices of the pathogenic antigen binding capacity, complement activation activity and FcγRs binding activity in Chinese preparations were 152%, 143% and 87%. The biological activities varied widely among the 7 IVIg preparations, and no significant differences were observed between the different batches of most IVIgs from the same manufacturer. This study will contribute to the improvement of the IVIg product quality evaluation system and an increased understanding of the variety of IgG biological activities in Chinese IVIg preparations.

Keywords: Biological activity; Complement activation; Fcγ-receptors binding; Intravenous immunoglobulin; Pathogenic antigen.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, Bacterial / immunology*
  • Cell Line
  • China
  • Complement Activation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / immunology*
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology*
  • Immunoglobulins, Intravenous / immunology
  • Immunoglobulins, Intravenous / pharmacology*
  • Immunologic Deficiency Syndromes / drug therapy
  • Quality Improvement
  • Receptors, IgG / metabolism*
  • Reference Standards
  • Technology, Pharmaceutical / methods
  • Technology, Pharmaceutical / organization & administration
  • Technology, Pharmaceutical / standards

Substances

  • Antigens, Bacterial
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Receptors, IgG

Supplementary concepts

  • Immune Deficiency Disease