Towards Understanding the Mechanisms of Lupus

The Role of DNA-Collagen Binding in the Pathogenesis of Lupus

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Innovation

Systemic Lupus Erythematosus (SLE or Lupus) is an autoimmune disease that can affect many organs and systems in the body. There have been dramatic advances in understanding and care of patients with lupus. Still, however, the factors that cause lupus and the precise mechanisms of the disease remain unknown. A hallmark of lupus is the presence of antibodies to DNA. The pediatric rheumatology research IDEA Lab is undertaking innovative experiments to better understand the role that DNA binding to collagen might play in the pathogenesis of lupus and the mechanisms by which tissue damage in target organs occurs.

Discovery

IDEA Lab research has shown that DNA binds to collagen including to the collagen that comprises the basement membrane of kidney glomeruli, a major site of pathology in lupus. The IDEA Lab has also shown that DNA binds to the collagen-like fragment of C1q and such an interaction might contribute to inciting activation of the complement cascade, a biologic feature typifying active lupus.

Engagement

Support for IDEA Lab lupus research was provided by the Lupus Society of Saskatchewan (Lupus SK), the Arthritis Society of Canada, and The College of Medicine, University of Saskatchewan. New collaborations are being explored, to better identify the molecular interactions between DNA and collagen using advanced imaging techniques, including synchrotron imaging.

Action

We believe that defining the precise molecular interactions between DNA and collagen molecules will help explain mechanisms of tissue damage in lupus and potentially inform the creation of entirely new therapeutic strategies based on DNA-collagen molecular interactions.