Antiribosomal P protein antibodies
- Donald B Bloch, MD
Donald B Bloch, MD
- Associate Professor of Medicine
- Harvard Medical School
Autoantibodies directed against three phosphorylated protein (“P protein”) components of ribosomes are present in a minority of patients with systemic lupus erythematosus (SLE) and are highly specific for this disease. Some studies have suggested that these antibodies may serve as markers for specific disease manifestations, including central nervous system (CNS) disease and hepatitis, but other studies have not confirmed these associations. (See 'Associations with specific manifestations of SLE' below.)
The specificity, clinical associations, and utility of measuring antiribosomal P protein antibodies are discussed here. An overview of antinuclear antibodies and the approach to the diagnosis of CNS disease in SLE are presented separately. (See "Measurement and clinical significance of antinuclear antibodies" and "Diagnostic approach to the neuropsychiatric manifestations of systemic lupus erythematosus".)
ANTIBODIES TO RIBOSOMAL P PROTEINS
Antigen specificity — The targets of antiribosomal antibodies found in the sera of some patients with systemic lupus erythematosus (SLE) are three highly conserved phosphorylated proteins (P proteins) located on the 60S subunit of ribosomes [1,2]. The P proteins, which exhibit molecular weights of 35, 19, and 17 kD, are designated P0, P1, and P2, respectively. The immunodominant epitope in patients with SLE is a shared sequence at the carboxy (C)-termini of the P proteins [3-5].
In their native form, the ribosomal P antigens form a pentamer consisting of one copy of P0 and two copies each of P1 and P2. This complex interacts with the 28S ribosomal RNA molecule to form the ribosomal stalk, including a guanosine triphosphatase (GTPase) domain involved in the elongation step of protein translation . Monoclonal antibodies to P proteins inhibit binding of elongation factor (EF)-1 alpha and EF-2 to ribosomes and inhibit protein synthesis [7,8].
P proteins were initially identified on ribosomes in the cytoplasm ; subsequent studies have also documented epitopes recognized by antiribosomal P protein antibodies on the surface of neuronal, hepatoma, and activated T cells in vitro [10,11]. The binding of antibodies to these proteins on cell surfaces could have pathogenic significance, given evidence that such antibodies can be internalized, resulting in cellular dysfunction [6,12].
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- ANTIBODIES TO RIBOSOMAL P PROTEINS
- Antigen specificity
- Antibody detection
- DISEASE ASSOCIATIONS
- ASSOCIATIONS WITH SPECIFIC MANIFESTATIONS OF SLE
- CNS disease
- Liver disease
- Renal disease
- Skin disease
- Other associations
- CLINICAL UTILITY OF ANTIRIBOSOMAL P ANTIBODIES
- SUMMARY AND RECOMMENDATIONS