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Autoantibodies and SLE—the threshold for disease

Abstract

The presence of autoantibodies in apparently healthy individuals has been increasingly recognized. Although some of these individuals are in preclinical stages of a disease such as systemic lupus erythematosus (SLE), many will not develop SLE or any other autoimmune disorder. The high prevalence of autoreactivity in the population in fact suggests that autoantibodies are expressed as part of a healthy immune response, and other data have clearly shown that some autoantibodies have important immune regulatory functions. These observations leave open questions regarding when and how benign autoimmunity develops into disease. If the transition from preclinical autoimmunity to a clinical disorder such as SLE could be predicted, early and thus potentially more effective intervention might be possible and cures might even become a reality. Furthermore, increased understanding of mechanisms by which autoantibodies are kept in check can identify new approaches to aborting or preventing disease transformations. In this article, we summarize the current findings regarding the presence of SLE-associated antibodies in apparently healthy individuals, and provide our opinions on what such discoveries might tell us about the roles of autoantibodies in the development of disease.

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Figure 1: Factors influencing progression from serological autoimmunity to stages of clinically manifested symptoms.
Figure 2: Schematic presentation of the progression from benign preclinical autoimmunity to organ involvement in SLE, outlining key pathogenetic processes and clinical features.

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Acknowledgements

The authors gratefully acknowledge Catherine Abendroth, Penn State Milton S. Hershey Medical Center, PA, USA, and Kari Connolly, University of California San Francisco Medical Center, CA, USA, for providing photomicrographs used in Figure 2.

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Both authors made substantial contributions to all stages of the preparation of this manuscript for submission.

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Correspondence to Nancy J. Olsen.

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N. J. Olsen has received research funding from NovoNordisk, Questcor, Roche/Genentech and Savient, and has an equity interest in ArthroChip. D. R. Karp has received research funding from BMS, Human Genome Sciences/GSK, Janssen and Sanofi.

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Olsen, N., Karp, D. Autoantibodies and SLE—the threshold for disease. Nat Rev Rheumatol 10, 181–186 (2014). https://doi.org/10.1038/nrrheum.2013.184

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