Document Detail


Anticomplementary activity of IVIG concentrates--important assay parameters and impact of IgG polymers.
MedLine Citation:
PMID:  20432511     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: A high concentration of large size polymers in intravenous immunoglobulin preparations was always correlated with high anticomplementary activity (ACA). In former days, high ACA was also linked to adverse reactions in patients. The goal of this study was to scrutinize critical parameters of the ACA assay and the influence of different polymer variants of IgG on the complement consumption. MATERIALS AND METHODS: Critical reagents as the complement and the preparation of erythrocytes were investigated. The influence of molecular integrity of IgG on the ACA was tested by subjecting IgG solutions ranging from pH 4.5 to 7.0 to heat treatment at 60 degrees C. RESULTS: The different complement batches had a significant impact on the test result of the ACA assay. It was demonstrated that polymers, provoked by heat treatment at pH values above 5.5, consumed complement almost completely whereas a polymer content up to 12% formed under acidic conditions did not lead to an increase in ACA. CONCLUSION: It was shown that suitable complement batches have to be identified in a screening procedure. Furthermore, it could be demonstrated that IgG polymers formed in the neutral pH range during heat treatment were potential ACA inducing compounds. Manufacturing the IVIG preparations under acidic conditions may help to avoid the formation of those ACA active polymers. Thus, intensive analysis of ACA during process development and validation is recommended.
Authors:
A Buchacher; P Schluga; J Müllner; M Schreiner; C Kannicht; J Weinberger
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Vox sanguinis     Volume:  98     ISSN:  1423-0410     ISO Abbreviation:  Vox Sang.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-29     Completed Date:  2010-07-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413606     Medline TA:  Vox Sang     Country:  England    
Other Details:
Languages:  eng     Pagination:  e209-18     Citation Subset:  IM    
Affiliation:
Octapharma Pharmazeutika ProduktionsGmbH, Vienna, Austria. andrea.buchacher@octapharma.at
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MeSH Terms
Descriptor/Qualifier:
Animals
Artifacts*
Chromatography, Gel
Complement Activation*
Complement System Proteins / chemistry
Guinea Pigs
Hemolysis
Hot Temperature
Humans
Hydrogen-Ion Concentration
Immunoglobulin G / immunology*
Immunoglobulins, Intravenous / adverse effects*,  immunology
Indicators and Reagents
Nephelometry and Turbidimetry
Reproducibility of Results
Sheep
Chemical
Reg. No./Substance:
0/Immunoglobulin G; 0/Immunoglobulins, Intravenous; 0/Indicators and Reagents; 0/polymeric IgG; 9007-36-7/Complement System Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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