These authors contributed equally to this work.
Dedicated removal of immunoglobulin (Ig)A, IgM, and Factor (F)XI/activated FXI from human plasma IgG
Article first published online: 23 MAY 2013
© 2013 American Association of Blood Banks
Volume 54, Issue 1, pages 169–178, January 2014
How to Cite
Wu, Y.-W., Champagne, J., Toueille, M., Gantier, R. and Burnouf, T. (2014), Dedicated removal of immunoglobulin (Ig)A, IgM, and Factor (F)XI/activated FXI from human plasma IgG. Transfusion, 54: 169–178. doi: 10.1111/trf.12243
This work was supported by Pall Life Sciences and Taipei Medical University (TMU101-AE1-B09 grant).
- Issue published online: 9 JAN 2014
- Article first published online: 23 MAY 2013
- Manuscript Revised: 30 MAR 2013
- Manuscript Accepted: 30 MAR 2013
- Manuscript Received: 13 MAR 2013
- Pall Life Sciences
- Taipei Medical University. Grant Number: TMU101-AE1-B09
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.
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.
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.