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Open Access Research article

Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis

Lu Gan1, Terrance P O’Hanlon1, Aaron S Gordon2, Lisa G Rider1, Frederick W Miller1* and Peter D Burbelo2*

Author Affiliations

1 Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, Bethesda, MD, USA

2 Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

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BMC Musculoskeletal Disorders 2014, 15:67  doi:10.1186/1471-2474-15-67

Published: 6 March 2014

Abstract

Background

Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions.

Methods

In this cross-sectional study, thirty-one monozygotic or dizygotic twin pairs discordant for myositis or systemic lupus erythematosus (SLE), along with matched healthy controls were evaluated for antibodies against a panel of 21 autoantigens.

Results

Autoantibody profiling revealed that 42% of the affected twins showed significant seropositivity against autoantigens in the panel. In many of these affected twins, but none of healthy controls, there were high levels of autoantibodies detected against two or more autoantigens commonly seen in systemic autoimmune diseases including Ro52, Ro60, RNP-70 K and/or RNP-A. In contrast, only 10% (3/31) of the unaffected twins showed seropositivity and these immunoreactivities were against single autoantigens not seen in systemic autoimmune diseases. While no significant differences in autoantibodies were detected between the affected or unaffected twins against thyroid peroxidase, transglutaminase and several cytokines, 23% of the affected twins with myositis showed autoantibodies against the gastric ATPase. Analysis of the monozygotic twins separately also revealed a higher frequencies of autoantibodies in the affected twins compared to the unaffected twins (P = 0.046). Lastly, clinical analysis of both the affected monozygotic and dizygotic twins revealed that the autoantibody seropositive affected twins had a greater global disease activity score compared to seronegative affected twins (P = 0.019).

Conclusion

The findings of significantly more autoantibodies in the affected twins with myositis and SLE compared to the unaffected twins are consistent with potential non-genetic factors playing a role in autoantibody production and pathogenesis of these autoimmune disorders.