What Is the Interferon Signature Test for AGS?

The interferon signature is a specialized blood test that measures whether a child’s immune system is stuck in “overdrive.” Specifically, it looks at the activity driven by a chemical messenger called Type I Interferon, which is unusually active in children with Aicardi-Goutières syndrome (AGS) ^[1][2]. Doctors use this test initially to help diagnose the condition, and later to periodically monitor how well treatments are working to calm the immune system ^[3].

What Does the Test Actually Measure?

In a healthy body, interferon acts as an alarm system to fight off viral infections. In AGS, genetic differences cause the body to trigger this alarm constantly, even when no virus is present, creating chronic inflammation ^[4].

The blood test doesn’t just measure the interferon itself. Instead, it measures interferon-stimulated genes (ISGs)—the specific genes in the body’s cells that are “turned on” by this false alarm ^[5][1]. When a large number of these genes are highly active, the test result shows an elevated “interferon signature.”

Why is it Used for Diagnosis?

Because AGS is classified as an “interferonopathy”—a disease caused by too much interferon—finding an elevated signature is a powerful clue that helps doctors confirm an AGS diagnosis ^[6]. It is especially helpful in making a diagnosis when a child’s genetic testing results are uncertain ^[7]. The signature can sometimes even be detected in the newborn period, before major clinical symptoms appear ^[8].

However, a normal or negative test does not completely rule out AGS. Children with certain specific genetic mutations, such as the RNASEH2B mutation, are more likely to have a lower or negative interferon signature compared to those with other AGS genes ^[9][8].

What to Expect: Logistics and Lab Results

Because the interferon signature test is highly specialized, it usually cannot be processed by a local pediatrician’s standard lab. The blood sample typically needs to be sent to a specific research or reference laboratory ^[5]. As a result, it can take several weeks to get the results back. The test typically does not require fasting.

When reviewing the results on a lab portal, you won’t see a single “interferon level.” Instead, you will see a composite “score” calculated from the activity of multiple ISGs. Every specialty lab has its own scale for what constitutes a “normal” versus “elevated” score, so your doctor will compare your child’s score against that specific lab’s baseline ^[3].

Crucially, because the test measures immune response, an ordinary viral infection (like a common cold) at the time of the blood draw can temporarily spike the score. Always tell your doctor if your child was sick when the blood was drawn, as this provides important context for interpreting the results.

Why Does My Child Need the Test Repeatedly?

Once a child is diagnosed with AGS, doctors will order the interferon signature test periodically for two main reasons:

• Monitoring Medication Effectiveness: If your child is prescribed a JAK inhibitor (such as baricitinib), this medication works specifically by blocking the harmful interferon alarm signals ^[10][11]. Doctors use the interferon signature test to verify that the medication is doing its job. A dropping interferon score is one sign that the drug is helping to calm the immune overdrive, though your doctor will also look closely at clinical improvements ^[12][13]. It can take weeks or months of consistent medication use to see significant changes in the score.
• Tracking Overall Disease Activity: The signature serves as a biomarker to help doctors see how active the underlying inflammation is over time ^[3].

While the test is excellent for measuring internal inflammation, it does have limitations. Research shows that a child’s interferon score does not always perfectly match their clinical symptoms or predict their future neurological development ^[14][5]. Therefore, doctors will always look at the test results alongside your child’s physical health, developmental progress, and symptom history.