TITLE:
Plasma Proteome Profiling with Monoclonal Antibody Libraries: A Pilot Biomarker Analysis for Nanomedicine-Induced Complement Activation
AUTHORS:
János Szebeni, Zsóka Weiszhár, Zoltán Rozsnyay, Todd Martinsky, János Kádas, József Lázár, László Takács, István Kurucz
KEYWORDS:
Hypersensitivity Reactions; Complement Factor H; Serum Amyloid P; Proteome Profiling; Biomarkers
JOURNAL NAME:
Advances in Nanoparticles,
Vol.2 No.2,
May
25,
2013
ABSTRACT:
Complement (C) activation-related hypersensitivity reactions (HSRs) represent an unsolved adverse immune effect of many i.v. administered “nanomedicines”, such as liposomal doxorubicin (Doxil/Caelyx). Because these pseudoallergic reactions can be severe or even lethal, it is an important clinical objective to find biomarkers for proneness for C activation by reactogenic nanoparticles that will allow the prediction of in vivo reactions by in vitro assays. With this goal in mind we identified a normal human blood donor who consistently showed high sensitivity to Caelyx-induced C activation in vitro, whose plasma (Caelyx sensitive plasma, CSP) was subjected to proteome profiling with a library of human plasma proteome specific mAbs. The chip (PlasmaScan-380TM) contained 380 non redundant (with respect to epitopes) mAbs. The analysis revealed 8 proteins that were differentially represented in CSP in comparison with Caelyx-insensitive control plasma. These proteins were identified by mass spectrometry and Western blot analyses to represent factor H (decreased in CSP), factor H related protein, serum amyloid P component, fibronectin, complement component C4, Apo B100, prothrombin and alpha-2-HS glycoprotein (all increased in CSP). Some of these protein changes are consistent with proneness for increased C activation, suggesting the potential use of this method in the search for biomarkers for liposome-induced or other types of nanomedicine-induced HSRs.