Journal of Molecular Medicine

, Volume 85, Issue 9, pp 953–959

Diverse humoral autoimmunity to the ribosomal P proteins in systemic lupus erythematosus and hepatitis C virus infection

  • K. Kessenbrock
  • M. J. Fritzler
  • M. Groves
  • P. Eissfeller
  • C. A. von Mühlen
  • P. Höpfl
  • M. Mahler
Rapid Communication

DOI: 10.1007/s00109-007-0239-5

Cite this article as:
Kessenbrock, K., Fritzler, M.J., Groves, M. et al. J Mol Med (2007) 85: 953. doi:10.1007/s00109-007-0239-5

Abstract

Autoantibodies to the three ribosomal P proteins (Rib-P) are specifically found in 10% to 40% of systemic lupus erythematosus (SLE) patients. Most anti-Rib-P autoantibodies bind to a C-terminal epitope shared by all three Rib-P proteins P0, P1 and P2. In the present study, we shed more light on the humoral autoimmune response to the Rib-P antigen as it occurs in autoimmunity and infectious disease. In a mutational analysis of the major C-terminal epitope, we verified the key role of phenylalanine residues Phe111 and Phe114 for binding of most anti-Rib-P serum autoantibodies present in SLE sera (n = 28). By nuclear magnetic resonance (NMR) investigation of a peptide comprising the C-terminal 22 amino acids, we observed hallmarks for α-helical secondary structure of the Rib-P epitope core (GFGLFD). Based on NMR data and on SPOT epitope analysis, we propose a structural model of the Rib-P major epitope, which displays Phe111 and Phe114 on one side of the helix. Apart from that, two sera from the hepatitis C virus (HCV) control group (n = 68) were found to contain antibodies specific for P2, but not for the other Rib-P proteins. Using a SPOT peptide array scanning the P2 amino acid sequence, we identified reactivity with two distinct epitopes (residues 21–35 and 41–55 of Rib-P2) shared by both HCV sera. We conclude that anti-Rib-P autoreactivity occurs in SLE, Chagas’ disease (CD) and—as firstly described here—during HCV infection. Anti-Rib-P reactivity in SLE sera primarily depends on Phe111 and Phe114 of the α-helical C-terminal epitope. In contrast, anti-Rib-P autoantibodies in HCV infection mainly recognize epitopes within the N-terminal half of ribosomal P2.

Keywords

Autoantibodies SLE HCV Ribosomal P Peptide Lupus 

Supplementary material

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • K. Kessenbrock
    • 1
    • 8
  • M. J. Fritzler
    • 2
  • M. Groves
    • 3
  • P. Eissfeller
    • 4
  • C. A. von Mühlen
    • 5
  • P. Höpfl
    • 6
  • M. Mahler
    • 7
  1. 1.University of HeidelbergHeidelbergGermany
  2. 2.Faculty of MedicineUniversity of CalgaryAlbertaCanada
  3. 3.EMBL Outstation HamburgHamburgGermany
  4. 4.Mikrogen GmbHNeuriedGermany
  5. 5.Pontifical Catholic University School of MedicinePorto AllegreBrazil
  6. 6.Phadia GmbHFreiburgGermany
  7. 7.Dr. Fooke Laboratorien GmbHNeussGermany
  8. 8.Max Planck Institute of NeurobiologyMartinsriedGermany

Personalised recommendations