Article Text
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems triggered by the production of autoantibodies. Previous clinical studies in humans and murine models suggest that type I interferons (IFNs) are important for the initiation and potentiation of SLE activity.
Methods: 65 consecutive patients with SLE were identified from the University of California, San Francisco Lupus Clinic with moderate-severe disease activity. 94 serological samples were collected. Type I IFN levels and the ability of plasma to induce expression of several surface markers of dendritic cell maturation were measured.
Results: Type I IFN levels correlated with the presence of cutaneous manifestations, and there was a trend towards correlation with renal disease. No correlation was found between type I IFN levels and neurological disease. Type I IFN levels correlated positively with the SLEDAI score and anti-dsDNA levels and inversely with C3 levels. Interestingly, type I IFN levels were highest in African American patients. SLE plasma also induced the expression of MHC class I, CD38, and CD123 on monocytes, and was blocked by the addition of a monoclonal antibody to IFNAR1.
Conclusions: The pathogenic role of type I IFN is suggested by the induction of cell surface markers for dendritic cell maturation. The potential therapeutic utility of antibodies directed to either type I IFN or IFNAR1/IFNAR2 may be of interest in further studies.
- CI, confidence interval
- DCs, dendritic cells
- ESR, erythrocyte sedimentation rate
- GM-CSF, granulocyte monocyte-colony stimulating factor
- IFN, interferon
- IFNAR1, α chain of the receptor for type I IFN
- ISRE-Luc, IFN stimulated response element luciferase
- MHC, major histocompatibility complex
- PBMCs, peripheral blood mononuclear cells
- PBS, phosphate buffered saline
- SLE, systemic lupus erythematosus
- SLEDAI, Systemic Lupus Erythematosus Disease Activity Index
- SLEDAI
- interferon
- renal disease
- systemic lupus erythematosus
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- CI, confidence interval
- DCs, dendritic cells
- ESR, erythrocyte sedimentation rate
- GM-CSF, granulocyte monocyte-colony stimulating factor
- IFN, interferon
- IFNAR1, α chain of the receptor for type I IFN
- ISRE-Luc, IFN stimulated response element luciferase
- MHC, major histocompatibility complex
- PBMCs, peripheral blood mononuclear cells
- PBS, phosphate buffered saline
- SLE, systemic lupus erythematosus
- SLEDAI, Systemic Lupus Erythematosus Disease Activity Index