The authors have applied for an Australian provisional patent (2007905935) for the flow cytometry method described in this article, for identifying subjects with, or susceptible to, systemic lupus erythematosus.
Systemic Lupus Erythematosus Basic Science Studies
A B cell apotope of Ro 60 in systemic lupus erythematosus†
Version of Record online: 27 MAR 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 4, pages 1125–1129, April 2008
How to Cite
Reed, J. H., Jackson, M. W. and Gordon, T. P. (2008), A B cell apotope of Ro 60 in systemic lupus erythematosus. Arthritis & Rheumatism, 58: 1125–1129. doi: 10.1002/art.23377
- Issue online: 27 MAR 2008
- Version of Record online: 27 MAR 2008
- Manuscript Accepted: 28 DEC 2007
- Manuscript Received: 19 OCT 2007
- Australian National Health and Medical Research Council
- Australian Postgraduate Award
Previous studies have attempted to segregate anti–60-kd Ro/SSA (anti–Ro 60) responses in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) but have shown limited disease preference. The aim of the present study was to determine whether the presence of autoantibodies against an Ro 60 apotope (an epitope expressed on apoptotic cells) distinguishes anti–Ro 60 responses in SLE and primary SS.
Multiparameter flow cytometry was used to select early apoptotic cells and measure the simultaneous binding of annexin V, propidium iodide, and anti–Ro 60–positive IgG from SLE patients (n = 21) and patients with primary SS (n = 19). The specificity of the Ro 60 apotope was determined by inhibition experiments with recombinant and native Ro 60.
Autoantibodies against the Ro 60 apotope were prevalent in SLE patients (13 of 21, 62%) and were rarely observed in patients with primary SS (1 of 19, 5%) (P = 0.0002). Further, within SLE patients, autoantibodies to the Ro 60 apotope strongly distinguished patients with anti–Ro 60 alone (12 of 13, 92%) from those with both anti–Ro 60 and anti-La (1 of 8, 13%) (P = 0.0005). When we considered all patients with anti–Ro 60 alone, the presence of autoantibodies to the Ro 60 apotope had both high sensitivity (92.3%) and high specificity (85.7%) for SLE compared with primary SS (P = 0.0012). The presence of autoantibodies to the Ro 60 apotope may therefore be of diagnostic value in patients with isolated anti–Ro 60 responses.
The preferential targeting of an Ro 60 apotope exposed on early apoptotic cells in a subset of SLE patients implies disease-specific pathways for the induction of anti–Ro 60 autoimmunity.