Poster Presentation 11th Australian Peptide Conference 2015

Peptide neutralization of autoantibodies (#124)

Sunithi Gunasekera 1 , Cátia Fernandes-Cerqueira 2 , Camilla Eriksson 1 , Per-Johan Jakobsson 2 , Ulf Göransson
  1. Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
  2. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

Over the last years, our research has focused on discovery, engineering, and synthesis of ultra stable peptides with the overall aim to find applications in biotechnology and medicine (1,2). Currently, we capitalize on such scaffold peptides in the development of a new strategy for diagnosis and treatment of autoimmune diseases: neutralization of pathogenic autoantibodies using peptide blockers (3).

Rheumatoid arthritis is an autoimmune disease, which is characterized by chronic inflammation, destruction of joints, and pain. The aetiology of the disease is still unclear, but a major part—60 to 70%— of persons suffering of rheumatoid arthritis carry autoantibodies against citrullinated proteins. In fact, the presence of anti-citrullinated protein/peptide antibodies (ACPAs) is one of the specific serological diagnostic markers of the disease. ACPAs emerge as an immune response towards proteins containing citrulline, which are the results of specific enzymes, peptidylarginine deiminases, converting arginine to citrulline.

We have shown that short peptide blockers are able to neutralize ACPAs (4). These peptide blockers are based on the discovery of specific citrullinated protein sequences that trigger autoimmune responses, which then are incorporated into the peptide scaffolds to improve stability and binding properties.

  1. Burman, R., Gunasekera, S., Strömstedt, A.A., and Göransson, U. (2014). Chemistry and biology of cyclotides: circular plant peptides outside the box. J Nat Prod 77, 724-736.
  2. Göransson, U., Burman, R., Gunasekera, S., Strömstedt, A.A., and Rosengren, K.J. (2012). Circular proteins from plants and fungi. J Biol Chem 287, 27001-27006.
  3. Fernandes-Cerqueira, C., Klareskog, L., and Jakobsson, P.J. (2014). Neutralization of anticitrullinated protein antibodies in rheumatoid arthritis - a way to go? Basic Clin Pharmacol Toxicol 114, 13-17.
  4. Fernandes-Cerqueira, C., Ossipova, E., Gunasekera, S., Hansson, M., Mathsson, L., Catrina, A.I., Sommarin, Y., Klareskog, L., Lundberg, K., Ronnelid, J., Göransson, U., and Jakobsson, P.J. (2015). Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens. Arthritis Res Ther 17, 155.