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Dedicated removal of immunoglobulin (Ig)A, IgM, and Factor (F)XI/activated FXI from human plasma IgG

Authors

  • Yu-Wen Wu,

    1. Institute of Medical Biomaterials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    2. Research and Development, Chromatography Applications, Pall Life Sciences, Cergy, France
    3. Pall Life Sciences, Northborough, Massachusetts
    4. Human Protein Process Sciences (HPPS), Lille, France
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    • These authors contributed equally to this work.
  • Jérôme Champagne,

    1. Institute of Medical Biomaterials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    2. Research and Development, Chromatography Applications, Pall Life Sciences, Cergy, France
    3. Pall Life Sciences, Northborough, Massachusetts
    4. Human Protein Process Sciences (HPPS), Lille, France
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    • These authors contributed equally to this work.
  • Magali Toueille,

    1. Institute of Medical Biomaterials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    2. Research and Development, Chromatography Applications, Pall Life Sciences, Cergy, France
    3. Pall Life Sciences, Northborough, Massachusetts
    4. Human Protein Process Sciences (HPPS), Lille, France
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  • René Gantier,

    1. Institute of Medical Biomaterials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    2. Research and Development, Chromatography Applications, Pall Life Sciences, Cergy, France
    3. Pall Life Sciences, Northborough, Massachusetts
    4. Human Protein Process Sciences (HPPS), Lille, France
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  • Thierry Burnouf

    Corresponding author
    1. Institute of Medical Biomaterials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    2. Research and Development, Chromatography Applications, Pall Life Sciences, Cergy, France
    3. Pall Life Sciences, Northborough, Massachusetts
    4. Human Protein Process Sciences (HPPS), Lille, France
    • Address reprint requests to: Thierry Burnouf, Institute of Medical Biomaterials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; e-mail: tburnou@attglobal.net.

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  • This work was supported by Pall Life Sciences and Taipei Medical University (TMU101-AE1-B09 grant).

Abstract

Background

Adverse events can be associated with treating critically ill patients with immunoglobulin (Ig)G. Some adverse events are due to contaminants like IgA and activated Factor (F)XI. Therefore, new purification strategies are needed for dedicated removal of these contaminants without impairing IgG recovery.

Study Design and Methods

An immunoglobulin fraction containing IgG, IgM, and IgA was prepared by caprylic acid precipitation of cryoprecipitate-poor plasma. The capacities of the cation exchangers (S HyperCel and CM Ceramic HyperD F) and anion exchangers (HyperCel STAR AX and Q HyperCel) to remove IgA, IgM, and spiked FXI were tested following a design of experiment approach using microplates and chromatographic column scale-up. FXI removal was also evaluated using Mustang S chromatographic membranes. IgG/IgG subclasses, IgA, IgM, and FXI were assessed by enzyme-linked immunosorbent assay, and caprylic acid, by gas chromatography.

Results

Extensive removal of IgA and IgM, but not FXI, was achieved by a two-step chromatographic process combining S HyperCel used in the IgG binding and elution mode and HyperCel STAR AX used in the IgG flow-through mode, providing high IgG and IgG subclass recovery (>85%), high purity (>99.5%), and efficient removal of IgA (<0.5%) and IgM (undetectable). Twenty-six-fold FXI removal was achieved by processing the resulting purified IgG fraction through Mustang S cation-exchanger membranes at pH 6.0 and 12.7 mS/cm. Caprylic acid was removed by S HyperCel.

Conclusions

Combining S HyperCel and HyperCel STAR AX extensively removed IgA and IgM, with good IgG recovery. Mustang® S membranes can be used for dedicated removal of FXI.

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