Lupus is not the same for everyone. Molecules called biomarkers can highlight your body’s unique reaction to SLE. You may already be familiar with several SLE biomarkers like anti-dsDNA, C3, and C4 that are commonly used to monitor SLE disease activity. Meet the new kid on the block, IFN-1. IFN-1 is a measure of your body’s anti-viral immune activity, and it is a primary target for many of the new, most powerful SLE drugs in development. It is also a key indicator of risk for developing Lupus Nephritis.1 In this post, you’ll learn why monitoring IFN-1 and other biomarkers is important.
The first wave of biomarkers
One of the reasons Lupus is so difficult to diagnose is that the agents that are causing harm in an SLE patient are also present in healthy individuals. When our bodies are under attack by a virus, our immune system launches several different defense mechanisms. In people with autoimmune disease, those defenses aren’t only active when the immune system is challenged by a foreign invader; the immune system turns on the body’s own, otherwise healthy, cells.
Several immune system components are present at unusually high or unusually low levels in SLE patients. Measuring these biomarkers can be helpful in diagnosing and monitoring SLE.
Common biomarker tests measure an antibody that targets DNA for destruction called anti-dsDNA. Abnormally high anti-dsDNA levels are unique to SLE. Other immune system proteins called Complement proteins are present at abnormally low levels in SLE. Tests for two complement proteins, C3 and C4, are common as many patients experience a rapid drop in C3/C4 levels preceding a flareup.
IFN-1 the newest biomarker on the block
IFN-1 and its link to Lupus and other autoimmune diseases has been studied extensively over the last 20 years. We now know that higher IFN-1 levels correlate with an increased risk of an SLE-associated kidney disease called Lupus Nephritis.1 High IFN-1 levels also correlate with an increased risk of high disease severity and possibly increased risk of complications during pregnancy2, emergence of cutaneous lupus3, and premature cardiovascular disease .4,5 IFN-1 is also a potential biomarker for a patient’s response to Anifrolumab6, the newest FDA approved SLE drug. Because of its impact on all of these areas, IFN-1 status is being used to select patients for enrollment in drug clinical trials.
IFN-1 fast facts
- As many as 50% of SLE patients overexpress IFN-17
- IFN-1 status is stable in most patients
- SLE patients tend to fall into two distinct groups based on IFN-1 status: IFN-1 High or IFN-1 Low
- IFN1-High status correlates with a 3X greater risk of progression to Lupus Nephritis 8
- IFN1-High status correlates with increased disease severity 9
- IFN1-High status may also correlate with complications during pregnancy, emergence of cutaneous lupus, and premature cardiovascular disease
- People diagnosed with SLE before they’re 30 are more likely to be IFN-1 High 10
- Asians, Hispanics, and African Americans are more likely to be IFN-1 High 1
- IFN-1 High patients might consider more frequent monitoring including proteinuria screening and anti-dsDNA
- IFN-1 High patients might consider extra monitoring during pregnancy for preeclampsia and complications
- IFN-1 High patients may be candidates for more aggressive immunosuppression and clinical trial enrollment
- New drugs, such as Anifrolumab, target IFN-1
- Arriens, C. et al. Increased Risk of Progression to Lupus Nephritis for Lupus Patients with Elevated Interferon Signature. Submitted (2019).
- Andrade D et al, Interferon-β and Angiogenic Dysregulation in Pregnant Lupus Patients Who Develop Preeclampsia, 67(4): 977-987 (2015).
- Hile GA, Kahlenberg JM. Immunopathogenesis of skin injury in systemic lupus erythematosus. Curr Opin Rheumatol. 2021;33(2):173-180.
- Casey KA, Smith MA, Sinibaldi D, et al. Modulation of Cardiometabolic Disease Markers by Type I Interferon Inhibition in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2021;73(3):459-471.
- Hasni SA, Gupta S, Davis M, et al. Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus. Nat Commun. 2021;12(1):3391.
- Morand EF, Furie R, Tanaka Y, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020;382(3):211-221.
- Steinberg AD, Baron S, Talal N. The pathogenesis of autoimmunity in New Zealand mice, I. Induction of antinucleic acid antibodies by polyinosinic-polycytidylic acid. PNAS 63:1102–7 (1969).
- Arriens, C. et al. Increased Risk of Progression to Lupus Nephritis for Lupus Patients with Elevated Interferon Signature. Submitted (2019).
- E. Baechler and et al., “Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.,” Proc Natl Acad Sci U S A., pp. Mar 4;100(5):2610-5. Epub 2003 Feb 25., (2003).
- Abedi M et al, Type 1 Interferon Levels Correlates with Age of Diagnosis and Ethnicity in Systemic Lupus Erythematous, Arthritis Rheumatol. 70 (suppl 10) 2018
