Does measles IgM (Immunoglobulin M) disappear in latent Subacute Sclerosing Panencephalitis (SSPE)?

Measles IgM Does NOT Disappear in SSPE—It Persists Abnormally

No, measles IgM does not disappear in latent SSPE; instead, it persists abnormally throughout all stages of the disease, which is a key diagnostic feature that distinguishes SSPE from acute measles infection. 1, 2

Understanding the Abnormal IgM Persistence

In acute measles infection, IgM antibodies follow a predictable timeline: they become detectable 1-2 days after rash onset, peak around 7-10 days, and become undetectable within 30-60 days after rash onset. 3, 1 This is the normal immune response pattern.

SSPE completely violates this normal pattern. All SSPE patients, regardless of disease stage (early, latent, or advanced), maintain persistently elevated measles-specific IgM antibodies in both serum and CSF—even years after the initial measles infection when viremia has long resolved. 1, 2, 4

Why IgM Persists: The Pathophysiology

The continuing release of measles antigen from persistent mutant measles virus in the CNS prevents the normal shut-off of IgM synthesis. 2 This is fundamentally different from acute infection:

• Acute measles: Virus is cleared → IgM production stops → IgM disappears by 30-60 days 3
• SSPE: Persistent CNS virus → continuous antigen release → IgM production never stops → IgM remains elevated indefinitely 2, 5

SSPE results from persistent mutant measles virus infection specifically localized to the CNS, occurring years after the initial measles infection when systemic viremia is no longer present. 1 The virus persists as defective viral clones that cannot form complete virus particles but can spread cell-to-cell within the CNS. 5

Diagnostic Significance: IgM as a Marker of Persistent Infection

The presence of measles-specific IgM in serum years after potential measles exposure strongly suggests SSPE. 1 This is because:

• In 35% of SSPE cases, the specific IgM response is more pronounced in CSF than in serum, indicating local IgM production within the CNS itself 2
• IgM levels remain constant over the course of SSPE when followed for 3-6 months, showing no tendency to disappear 4
• The detection of virus-specific IgM antibodies in CSF of patients with chronic CNS diseases indicates viral persistence 2

Clinical Algorithm for Diagnosis

When SSPE is suspected (progressive neurological deterioration with history of measles):

1. Obtain simultaneous serum and CSF samples for measles antibody testing 1
2. Test for measles-specific IgM in both serum and CSF—persistent IgM presence supports SSPE diagnosis 1, 2, 4
3. Calculate CSF/serum measles antibody index for IgG—values ≥1.5 confirm intrathecal synthesis 1
4. Combined criteria: Persistent IgM + elevated IgG + CSF/serum antibody index ≥1.5 achieves 100% sensitivity and 93.3% specificity for SSPE diagnosis 1

Critical Caveat: Distinguishing from Acute Measles

The IgM timeline is the key distinguishing feature:

• If IgM appeared recently and patient has acute illness: Consider acute measles or measles encephalitis 3
• If IgM has been persistently elevated for months/years with progressive neurological symptoms: Think SSPE 1, 2

One case report documented a patient with suspected recurrent measles encephalitis who maintained high anti-measles IgM titers for 6 years, suggesting chronic measles virus infection and possible latent SSPE. 6 This underscores that IgM persistence is the hallmark, not disappearance.

Why This Matters Clinically

The persistent IgM in SSPE reflects the immune system's inability to clear the CNS infection despite functional cell-mediated immunity and high antiviral antibody titers. 7 This abnormal persistence is both a diagnostic marker and a reflection of the underlying pathophysiology—the virus has established a persistent infection that the immune system cannot eliminate. 5