Long-term Ro60 humoral autoimmunity in primary Sjogren's syndrome is maintained by rapid clonal turnover

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Jul-13, 2013-07-01
Lindop, Rhianna
Arentz, Georgia
Bastian, Isabell
Whyte, Andrew F
Thurgood, Lauren Alexandra
Chataway, Timothy Kennion
Jackson, Michael W
Gordon, Thomas Paul
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Crown copyright 2013 Published by Elsevier Inc. All rights reserved.
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Elsevier Ltd.
Long-term humoral autoimmunity to RNA–protein autoantigens is considered a hallmark of systemic autoimmune diseases. We use high resolution Orbitrap mass spectrometric autoantibody sequencing to track the evolution of a Ro60-specific public clonotypic autoantibody in 4 patients with primary Sjögren's syndrome. This clonotype is specified by a VH3–23/VK3–20 heavy and light chain pairing. Despite apparent stability by conventional immunoassay, analysis of V-region molecular signatures of clonotypes purified from serum samples collected retrospectively over 7 years revealed sequential clonal replacement. Prospective longitudinal studies confirmed clonotype loss and replacement at approximately three-monthly intervals. Levels of secreted anti-Ro60 clonotypes fluctuated markedly over time, despite minimal changes in clonal affinity. Our novel findings indicate a relentless turnover of short-lived clonotypic variants, masquerading as long-lived Ro60 humoral autoimmunity.
This article appeared in a journal published by Elsevier Ltd. Under Elsevier's copyright, mandated authors are not permitted to make work available in an institutional repository.
Sjogren's syndrome, Autoimmunity, Ribonucleoproteins
Lindop, R., Arentz, G., Bastian, I., Whyte, A.F., Thurgood, L.A., Chataway, T.K., Jackson, M.W. and Gordon, T.P., 2013. Long-term Ro60 humoral autoimmunity in primary Sjogren's syndrome is maintained by rapid clonal turnover. Clinical Immunology, 148(1), 27-34.