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Contamination of therapeutic human immunoglobulin preparations with apolipoprotein H (β2‐glycoprotein I)
Author(s) -
Lackner Friedrich,
Beck Gerhard,
Eichmeir Stephanie,
Gemeiner Manfred,
Hummel Karin,
Pullirsch Dieter,
RazzaziFazeli Ebrahim,
Seifner Alexandra,
Miller Ingrid
Publication year - 2014
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201300319
Subject(s) - chemistry , immunoassay , polyclonal antibodies , transferrin , apolipoprotein b , antibody , thrombin , chromatography , albumin , in vivo , biochemistry , biology , cholesterol , immunology , microbiology and biotechnology , platelet
Polyclonal immunoglobulin (Ig) concentrates are important biological medicinal products and the assurance of their quality and safety is crucial. In our present approach we used proteomic methods to check the purity of commercial Ig products of different origin. The experimental setup included nonreducing 2 DE or DIGE combined with MALDI ‐ TOF and the thrombin generation assay, a routine safety test for pharmaceutical Ig preparations, and was complemented by a specific immunoassay. 2 DE patterns displayed contaminations with trace amounts of human apolipoprotein H ( A po‐ H ), transferrin, albumin, and its fragments. In contrast to the latter, A po‐ H is a protein that is active in the coagulation cascade, and thus a potential involvement in thromboembolic events in vivo cannot be excluded. It was found by 2 DE and MALDI ‐ TOF to be a contaminant of several Ig preparations. Spiking experiments of I g preparations with pure A po‐ H demonstrated an A po‐ H concentration dependent increase in thrombin generation assay values. Traces of A po‐ H are possibly also contributing to unwanted side effects, as already known for factor XI a. The significance of A po‐ H contaminations for these side effects might be verified by detailed analyses of pharmacovigilance data.