Drs. Colasanti and Maselli contributed equally to this work.
Systemic Lupus Erythematosus
Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus
Article first published online: 28 FEB 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 3, pages 778–787, March 2012
How to Cite
Colasanti, T., Maselli, A., Conti, F., Sanchez, M., Alessandri, C., Barbati, C., Vacirca, D., Tinari, A., Chiarotti, F., Giovannetti, A., Franconi, F., Valesini, G., Malorni, W., Pierdominici, M. and Ortona, E. (2012), Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus. Arthritis & Rheumatism, 64: 778–787. doi: 10.1002/art.33400
- Issue published online: 28 FEB 2012
- Article first published online: 28 FEB 2012
- Accepted manuscript online: 3 OCT 2011 09:57AM EST
- Manuscript Accepted: 29 SEP 2011
- Manuscript Received: 5 MAY 2011
- Ministero della Salute
- National Institute of Biostructures and Biosystems
Estrogens influence many physiologic processes and are also implicated in the development or progression of numerous diseases, including autoimmune disorders. Aberrations of lymphocyte homeostasis that lead to the production of multiple pathogenic autoantibodies, including autoantibodies specific to estrogen receptor (ER), have been detected in the peripheral blood of patients with systemic lupus erythematosus (SLE). This study was undertaken to assess the presence of both anti-ERα and anti-ERβ antibodies in sera from patients with SLE, to analyze the effect of these antibodies on peripheral blood T lymphocyte homeostasis, and to evaluate their role as determinants of disease pathogenesis and progression.
Anti-ER antibody serum immunoreactivity was analyzed by enzyme-linked immunosorbent assay in samples from 86 patients with SLE and 95 healthy donors. Phenotypic and functional analyses were performed by flow cytometry and Western blotting.
Anti-ERα antibodies were present in 45% of the patients with SLE, whereas anti-ERβ antibodies were undetectable. In healthy donors, anti-ERα antibodies induced cell activation and consequent apoptotic cell death in resting lymphocytes as well as proliferation of anti-CD3–stimulated T lymphocytes. A significant association between anti-ERα antibody values and clinical parameters, i.e., the SLE Disease Activity Index and arthritis, was found.
Our data suggest that anti-ERα autoantibodies interfere with T lymphocyte homeostasis and are significantly associated with lupus disease activity.