Title

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

Authors

Lu Gan, National Institute of Environmental Health Sciences, Bethesda, MD
Terence P. O'Hanlon, National Institute of Environmental Health Sciences, Bethesda, MD
Aaron S. Gordon, National Institutes of Health, Bethesda, MD
Lisa G. Rider, George Washington UniversityFollow
Frederick W. Miller, National Institute of Environmental Health Sciences, Bethesda, MDFollow
Peter D. Burbelo, National Institutes of Health, Bethesda, MD

Document Type

Journal Article

Publication Date

3-6-2014

Journal

BMC Musculoskeletal Disorders

Volume

Volume 15, Issue 1

Inclusive Pages

Article number 67

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.

Comments

Reproduced with permission of BioMed Central Musculoskeletal Disorders.

APA Citation

Gan, L., O'Hanlon, T.P., Gordon, A.S., Rider, L.G., Miller, F.W. et al. (2014). Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis. BMC Musculoskeletal Disorders, 15(1):67.

Peer Reviewed

1

Open Access

1