Altered Type II Interferon Predicts Risk of Systemic Lupus Erythematosus up to 3 Years Before Onset

Published November 2016
Annals of the Rheumatic Diseases

The most common form of lupus may be detectable as many as three years before the onset of classic markers for the disease, according to a multi-institutional study involving expertise at Cincinnati Children’s.

Approximately 200,000 to 300,000 Americans live with diagnosed systemic lupus erythematosus (SLE), according to previous studies. Lupus often causes extreme fatigue, joint pain and skin rashes. Over time, it can lead to dangerous organ damage. Typically, the condition is detected in patients between ages 15 and 45.

In some patients, immune system disruption and pathogenic autoantibody production can begin causing organ damage before they reach disease classification, which makes earlier detection and intervention an important goal.

Now, a longitudinal study that followed 55 people with lupus reveals that years before SLE classification, enhancement of the type II IFN pathway precedes accumulation of autoantibodies that can be detected at elevated levels.

“This study provides critical new information to help identify individuals at the highest risk of transition to SLE. Through the measurement of systemic soluble mediators indicative of ongoing inflammation when detected in the periphery, including IFN-g, IP-10, and MCP-3, in addition to the detection of DNA- and RNA-protein binding autoantibodies, we can identify individuals who may need rheumatology referral or closer monitoring,” the authors say.

John Harley, MD, PhD, director of CAGE, was a senior author in the study. He worked in collaboration with colleagues at the Oklahoma Medical Research Foundation, University of Oklahoma, the Mayo Clinic, Beth Israel Deaconess Medical Center, and Walter Reed National Military Medical Center.

Earlier detection of people at high risk for developing lupus may allow clinicians to provide potential early therapeutic agents, such as hydroxychloroquine, before irreversible organ damage has occurred.

These charts show the accumulation of interferon mediators (IFN) as the time of classification for systemic lupus erythematosus (SLE) approaches (upper chart) and the elevation of IFN-γ before there is other evidence of a process that will lead to SLE (lower chart).

Click image to enlarge.

Citation

Munroe ME, Lu R, Zhao YD, Fife DA, Robertson JM, Guthridge JM, Niewold TB, Tsokos GC, Keith MP, Harley JB, James JA. Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann Rheum Dis. 2016 Nov;75(11):2014-2021.

A photo of John Harley.

John Harley, MD, PhD