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Development of the anti-ribosomal P autoantibody response
H A Stafford1, C J Anderson, D B Blalock
1Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Objective:
Autoantibodies to the ribosomal P phosphoproteins (anti-P) appear almost exclusively in SLE. The mechanism by which these autoantibodies appear is unknown. The aim of this study was to determine if IgM and IgG isotype switching occurs during the development of the anti-P autoantibody response.
Methods:
Patients who acquired IgG anti-P during clinical observation had their serial serum samples from this period screened for IgM and IgG anti-P by immunoblots and ELISAs. Rabbits were immunized with the immunodominant peptide of the ribosomal P proteins ("P-peptide") cross-linked to bovine serum albumin. Their serial samples were also analyzed for IgM and IgG anti-P before and after repeated immunizations.
Results:
Two patients were identified who developed transient low titer IgM anti-P that preceded the development of their IgG anti-P. Both patients were clinically well during their peak of IgM anti-P, and developed flares of disease coincident with their high titered IgG anti-P response. The "P-peptide"-immunized rabbits developed an IgM anti-P response that preceded IgG anti-P, and that decreased over time.
Conclusion:
We conclude that IgM to IgG isotype switching occurs in the anti-P autoimmune response. These findings suggest that the autoimmune response to the ribosomal P proteins may be antigen-driven.