The Mystery of Antibodies Against Polyethylene Glycol (PEG) - What do we Know?
Recent findings demonstrated anti-PEG antibody formation in some healthy individuals and patients who have not received PEGylated biotherapeutics. Some of these findings evoked criticism because of shortcomings in the antibody assays used. To better understand this topic, we established robust antibody analytics and screened two cohorts of healthy individuals and one cohort of hemophilia patients for the expression of anti-PEG antibodies.



A flow cytometry approach and a fully validated ELISA platform were established to detect specific anti-PEG antibodies. Immunohistochemistry was used to test for potential binding of anti-PEG antibodies to human tissues.



IgM and/or IgG anti-PEG antibodies are expressed by some healthy individuals and by some patients with hemophilia who have not received PEGylated biotherapeutics. These antibodies can be either transient or persistent and recognize PEGs of different sizes with or without terminal methoxy groups. Age and location of healthy individuals influence the prevalence of IgG but not of IgM antibodies. Anti-PEG antibodies do not cross-react with human tissues supporting the safety of the antibodies.



We confirm that some healthy individuals and some patients with hemophilia express specific antibodies against PEG which are not associated with any pathology and do not bind to human tissues.
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria.
Christian
C
Lubich
IMC FH Krems, University for Applied Sciences, Krems, Austria.
Peter
P
Allacher
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria.
Maurus
M
de la Rosa
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria.
Alexander
A
Bauer
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria.
Thomas
T
Prenninger
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria.
Frank Michael
FM
Horling
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria.
Jürgen
J
Siekmann
Institute for Experimental Hematology and Transfusion Medicine, Bonn, Germany.
Johannes
J
Oldenburg
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria.
Friedrich
F
Scheiflinger
Baxalta Innovations GmbH, Industriestrasse 72, A-1220, Vienna, Austria. birgit.reipert@baxalta.com.
Birgit Maria
BM
Reipert
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006467:Hemophilia A / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D011092:Polyethylene Glycols / Q000378:metabolism*; D055815:Young Adult
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011092:Polyethylene Glycols
PEGylated proteins; anti-PEG antibodies in healthy individuals; anti-PEG antibodies in hemophilia patients; human tissue cross-reactivity study; specificity of anti-PEG antibodies