Type I Interferon Correlates with Clinical and Serologic Manifestations of Systemic Lupus Erythematosus

Maria C. Dall'Era ¹, Pina M. Cardarelli ², Benjamin T. Preston ², Alison Witte ² and John C. Davis ^1*

¹ University of California, San Francisco, United States
² Medarex company, United States

^* To whom correspondence should be addressed. E-mail: jdavis{at}medicine.ucsf.edu.

Accepted 14 April 2005

Abstract

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting multiple organ systems triggered by the production of various autoantibodies. Previous clinical studies in humans and murine models have suggested that type I interferons are important for the initiation and potentiation of SLE disease activity.

Methods: 65 consecutive patients with SLE were evaluated from the University of California, San Francisco (UCSF) Lupus Clinic with moderate-severe disease activity. A total of 94 serologic samples were collected. Type I interferon levels were then measured along with the ability of plasma to induce expression of several cell surface markers of dendritic cell maturation.

Results: Type I interferon levels correlated with the presence of cutaneous manifestations of SLE and there was a trend toward a correlation with renal involvement. We did not find a correlation between type I interferon levels and neurologic involvement. Type I interferon levels correlated positively with SLEDAI score and anti-dsDNA levels and inversely with C3 levels. Interestingly, type I interferon 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 IFNAR-1.

Conclusions: This is the largest study to date demonstrating the association between type I interferon and various clinical and serologic manifestations of SLE. The pathogenic role of Type I interferon is suggested by the cell surface marker induction, and the potential therapeutic utility of antibodies directed to either Type I interferon or IFNAR-1/IFNAR-2 may be of interest in further studies.

Keywords: SLEDAI, cutaneous, interferon, renal, systemic lupus erythematosus

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