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

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...

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Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2007-09, Vol.85 (9), p.953-959
Main Authors: KESSENBROCK, K, FRITZLER, M. J, GROVES, M, EISSFELLER, P, VON MÜHLEN, C. A, HÖPFL, P, MAHLER, M
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Autoantibodies - chemistry
Autoantibodies - immunology
Autoimmunity - immunology
Biological and medical sciences
Epitope Mapping
Epitopes - chemistry
Epitopes - immunology
General aspects
Hepatitis C - immunology
Humans
Lupus Erythematosus, Systemic - immunology
Magnetic Resonance Spectroscopy
Male
Medical sciences
Middle Aged
Molecular Sequence Data
Ribosomal Proteins - immunology
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
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Summary: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 Phe ( 111 ) and Phe ( 114 ) 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 alpha-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 Phe ( 111 ) and Phe ( 114 ) 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 Phe ( 111 ) and Phe ( 114 ) of the alpha-helical C-terminal epitope. In contrast, anti-Rib-P autoantibodies in HCV infection mainly recognize epitopes within the N-terminal half of ribosomal P2.
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-007-0239-5