Analytical and Bioanalytical Chemistry

, Volume 391, Issue 5, pp 1713–1720

Off-target activity of TNF-α inhibitors characterized by protein biochips

  • Oliver Feyen
  • Angelika Lueking
  • Axel Kowald
  • Christian Stephan
  • Helmut E. Meyer
  • Ulrich Göbel
  • Tim Niehues
Original Paper

DOI: 10.1007/s00216-008-1938-7

Cite this article as:
Feyen, O., Lueking, A., Kowald, A. et al. Anal Bioanal Chem (2008) 391: 1713. doi:10.1007/s00216-008-1938-7

Abstract

Tumor necrosis factor-alpha inhibitors are widely and successfully used to treat rheumatic diseases. However, significant side effects have been reported. To detect the potential off-target activities of such inhibitors we characterized two therapeutic antibodies (adalimumab, infliximab) and one receptor fusion protein (etanercept) on protein biochips (UNIchip® AV-400) containing a printed serial dilution of tumor necrosis factor-alpha and about 384 different human proteins. Etanercept binds to ten proteins (affinity: 20–33% of tumor necrosis factor-alpha recognition), and six of these proteins are related to ribosomal proteins. Interestingly, adalimumab binds to the same six proteins related to ribosomal proteins (affinity: 12–18%) as well as to four proteins crucially involved in ribosomal protein synthesis. Alignment of protein sequences indicates no significant sequence homology between these ten proteins bound by the biological drugs with the highest off-target activities. Taken together, our in vitro results demonstrate that a significant number of proteins are recognized by tumor necrosis factor-alpha inhibitors and are related to ribosome biogenesis.

Keywords

Specificity analysis Off-target activity Adalimumab Etanercept Infliximab Protein biochip 

Abbreviations

JIA

Juvenile idiopathic arthritis

OTA

Off-target activity

RA

Rheumatoid arthritis

RPL

Ribosomal protein (large subunit)

RPS

Ribosomal protein (small subunit)

SLE

Systemic lupus erythematosus

w/v

Weight per volume

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Oliver Feyen
    • 1
  • Angelika Lueking
    • 2
  • Axel Kowald
    • 3
  • Christian Stephan
    • 3
  • Helmut E. Meyer
    • 3
    • 4
  • Ulrich Göbel
    • 1
  • Tim Niehues
    • 1
  1. 1.Department of Pediatric OncologyHematology and Clinical Immunology, Jeffrey Modell Immunodeficiency Center, University Children’s Hospital DüsseldorfDüsseldorfGermany
  2. 2.Protagen AGDortmundGermany
  3. 3.Ruhr-University Bochum, Medizinisches Proteom-CenterBochumGermany
  4. 4.Medizinisches Proteom-Center, Ruhr-Universität BochumBochumGermany

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