Evidence Against Immunologically Silent SSPE Latency
SSPE latency is definitively NOT immunologically silent, as demonstrated by the persistent presence of measles-specific IgM antibodies in both serum and CSF throughout the disease course—a pathognomonic finding that reflects ongoing immune stimulation from continuous CNS viral replication. 1, 2
The Persistent IgM Signature Proves Ongoing Immune Activity
The most compelling evidence against immunologic silence comes from the abnormal persistence of measles-specific IgM antibodies:
In normal acute measles infection, IgM appears 1-2 days after rash onset, peaks at 7-10 days, and becomes completely undetectable within 30-60 days. 1, 3 This is the expected timeline for resolved infection.
In SSPE patients, measles-specific IgM remains persistently elevated in both serum and CSF for years or even decades, regardless of disease stage. 1, 2 This persistent IgM is highly abnormal and indicates continuous antigenic stimulation. 4
The levels of measles IgM are often higher in CSF (diluted 1:5) than in serum (diluted 1:50), confirming local CNS production rather than passive leakage from blood. 4 This intrathecal synthesis proves active immune responses within the CNS compartment.
Intrathecal Antibody Synthesis Demonstrates Active CNS Immunity
The gold standard diagnostic finding directly contradicts immunologic silence:
A CSF/serum measles antibody index (CSQrel) ≥1.5 confirms intrathecal synthesis of measles-specific IgG, indicating local CNS antibody production with 100% sensitivity and 93.3% specificity for SSPE diagnosis. 1, 2, 5
Oligoclonal bands specific to measles virus proteins are detectable by immunoblotting in CSF, demonstrating clonal expansion of B cells producing measles-specific antibodies within the CNS. 2, 6 The oligoclonal band patterns in CSF and serum show almost identical profiles, suggesting the same cell clones are active in both compartments. 6
Both anti-nucleocapsid and anti-matrix protein antibodies are synthesized intrathecally in SSPE patients, with geometric mean titers significantly elevated compared to controls. 7
Cellular Immune Responses Are Preserved
Beyond humoral immunity, cellular responses also remain active:
Lymphoproliferative responses to measles virus proteins (M, F, HA, and NC) are demonstrable in SSPE patients and not significantly different from healthy controls. 7 This indicates that T-cell recognition of viral antigens persists throughout the disease course.
The presence of both humoral and cellular immune responses to matrix protein specifically argues against a selective immune defect as the cause of viral persistence. 7
Clinical Implications of Continuous Immune Stimulation
The persistent immune activity has diagnostic and pathophysiologic significance:
The combination of persistent measles IgM in serum and CSF, elevated IgG, and CSF/serum measles antibody index ≥1.5 achieves 100% sensitivity and 93.3% specificity for SSPE diagnosis. 1, 2 This would be impossible if the latency period were immunologically silent.
Antibody titers remain constant over months of follow-up in individual SSPE patients, demonstrating sustained rather than intermittent immune activation. 4
The extremely high antibody titers with elevated CSF/serum index distinguish SSPE from other conditions, including the MRZ reaction in multiple sclerosis (which shows intrathecal synthesis against ≥2 of 3 viral agents) and acute measles reinfection (which shows high-avidity IgG with normal CSF/serum index). 1, 2
What "Latency" Actually Means in SSPE
The term "latency" in SSPE refers to the clinical silent period, not immunologic silence:
The 2-10 year interval (sometimes as short as 4 months) between acute measles infection and SSPE symptom onset represents a period without overt neurological symptoms, but the virus establishes persistent infection in neurons with trans-synaptic spread during this time. 1, 2, 8
During this "latent" period, there is no systemic viremia, but continuous low-level CNS viral replication drives ongoing immune responses. 1, 2 The mutant measles virus persists specifically in the CNS compartment with envelope protein mutations that facilitate cell-to-cell spread without viremia. 1