Why are measles Immunoglobulin G (IgG) levels typically high in patients with latent Subacute Sclerosing Panencephalitis (SSPE)?

Why Measles IgG Levels Are High in SSPE

In SSPE, measles IgG levels are dramatically elevated in both serum and CSF because the persistent, defective measles virus continuously replicates within the central nervous system, triggering ongoing antibody production—particularly intrathecal synthesis demonstrated by a CSF/serum measles antibody index ≥1.5. 1

Understanding the Pathophysiology

SSPE develops from persistent mutant measles virus infection specifically localized to the CNS, occurring years after the initial measles infection when systemic viremia has long resolved. 1 This is not a reactivation of latent virus, but rather continuous low-level viral replication within neurons that spreads trans-synaptically, with envelope proteins accumulating mutations over time. 1

The Continuous Immune Stimulation

The persistently elevated IgG levels reflect ongoing immune stimulation from continuous CNS viral replication, not a memory response from past infection. 1, 2 This is fundamentally different from normal post-measles immunity, where IgG develops during acute infection and persists at normal protective levels. 3

Key immunologic findings include:

• Dramatically elevated measles-specific IgG in both serum and CSF 1, 2
• Intrathecal antibody synthesis confirmed by CSF/serum measles antibody index ≥1.5, indicating local CNS production rather than systemic antibody leakage 1, 4
• Progressive rise in IgG levels correlating with disease stage and the progressive nature of the illness 5
• Oligoclonal bands specific to measles virus proteins detectable by immunoblotting 1

The Diagnostic Significance

The combination of persistently elevated measles IgG with a CSF/serum antibody index ≥1.5 has 100% sensitivity and 93.3% specificity for SSPE diagnosis. 1, 2 This intrathecal synthesis pattern is pathognomonic—it demonstrates that antibodies are being produced locally within the CNS in response to ongoing viral presence. 4

The Unusual IgM Persistence

Adding to the diagnostic picture, 100% of SSPE patients maintain detectable measles-specific IgM antibodies in both serum and CSF, which is highly abnormal since IgM typically disappears 30-60 days after acute measles. 1, 6 In 35% of SSPE cases, the specific IgM response is more pronounced in CSF than serum, suggesting IgM production within the CNS itself. 6

This persistent IgM reflects the continuing release of measles antigen as a result of virus persistence in the CNS, preventing the normal shut-off of IgM synthesis. 6 The detection of virus-specific IgM antibodies in CSF of patients with chronic CNS diseases can be taken as an indication of active viral persistence. 6

Critical Differential Diagnosis

The isolated, extremely strong measles-only antibody response distinguishes SSPE from:

• Multiple sclerosis with MRZ reaction: Shows intrathecal synthesis against at least 2 of 3 viral agents (measles, rubella, zoster), whereas SSPE shows only measles 1, 3
• Acute measles reinfection: Shows high-avidity IgG with IgM positivity but a normal CSF/serum index, whereas SSPE shows extremely high titers with elevated CSF/serum index ≥1.5 1
• Recent measles vaccination or infection: IgM becomes undetectable within 30-60 days, whereas in SSPE it remains persistently elevated for years 1, 3

The Immunologic Timeline

Understanding the phases clarifies why IgG is high:

1. Acute measles phase: Active viremia with robust immune response and antigen presentation 1
2. True latency period (typically 2-10 years): No systemic viremia, no active immune stimulation in most individuals 1
3. SSPE emergence: Insidious onset of neurological symptoms with reactivation of antibody production due to ongoing CNS viral replication 1, 5

The progressive increase in the ratio of CSF to serum IgG with disease advancement confirms local synthesis of IgG within the CNS, not just passive transfer from serum. 5

Common Pitfalls to Avoid

• Do not confuse elevated measles IgG in SSPE with normal post-infection or post-vaccination immunity—the magnitude and CSF/serum ratio are the distinguishing features 1
• Do not assume high IgG means recent infection—SSPE develops years after the initial measles exposure 1
• Always calculate the CSF/serum measles antibody index; elevated serum IgG alone is insufficient for diagnosis 1, 4
• Confirmatory testing using direct-capture IgM EIA method is recommended when IgM is detected without epidemiologic linkage to confirmed measles, as false-positives can occur in low-prevalence settings 1