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Ribosomal P autoantibodies are present before SLE onset and are directed against non-C-terminal peptides

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Abstract

Autoantibodies to ribosomal P (ribo P) are found in 15–30% of systemic lupus erythematosus (SLE) patients and are highly specific for SLE. The goal of this study is to assess the temporal association of anti-ribosomal P (anti-P) responses with SLE disease onset, as well as to characterize select humoral ribo P epitopes targeted in early, pre-diagnostic SLE samples. Patients with stored serial serum samples available prior to SLE diagnosis were identified from a military cohort. Each sample was tested for antibodies against ribo P utilizing standard C terminus ribo P enzyme-linked immunosorbent assays (ELISA) and a solid phase, bead-based assay with affinity-purified ribo P proteins. In this study, antibodies to ribo P were more common in African American SLE patients (p = 0.026), and anti-P-positive patients comprised a group with more measured autoantibody specificities than did other SLE patients (3.5 vs 2.2, p < 0.05). Antibodies against ribo P were present on average 1.7 years before SLE diagnosis and were detected an average of 1.08 years earlier in pre-diagnostic SLE samples using affinity-purified whole protein rather than C-terminal peptide alone (p = 0.0019). Furthermore, 61% of anti-P-positive patients initially had antibodies to aa 99–113, a known ribosomal P0 antigenic target, at a time point when no antibodies to the clinically used C terminus were detected. Our findings provide evidence that antibodies against ribosomal P frequently develop before clinical SLE diagnosis and are more broadly reactive than previously thought by targeting regions outside of the C terminus.

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Acknowledgments

The authors would like to thank Yasmin Akbarali MS, Roy Rindler MD, Tara Bruner PA-C, and Gabriel Vidal for their technical assistance and Scott Stewart MS for his statistical analysis assistance. This work has been supported by the National Institutes of Health (AI82714, AI31584, AR58554, AR45451, AI47575, AR53483, AR48045, AR45084, AR45231, AR42460, AR48940, AI24717, RR20143, RR15577, and RR14467), the Presbyterian Health Foundation, the Lou Kerr Chair in Biomedical Research, the Kirkland Foundation, and the US Department of Veteran Affairs. The opinions and assertions contained herein are private views of the authors and are not to be construed as official or as reflecting the views of the Army, Navy, or the Department of Defense.

Disclosures

John B. Harley serves as a consultant to Bio Rad Laboratories and as a consultant and member of the Board of Directors of IVAX Diagnostics.

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Correspondence to Judith A. James.

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Latisha D. Heinlen and Lauren L. Ritterhouse contributed equally to this work.

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Heinlen, L.D., Ritterhouse, L.L., McClain, M.T. et al. Ribosomal P autoantibodies are present before SLE onset and are directed against non-C-terminal peptides. J Mol Med 88, 719–727 (2010). https://doi.org/10.1007/s00109-010-0618-1

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