Does measles Immunoglobulin G (IgG) decline in patients with latent subacute sclerosing panencephalitis (SSPE)?

Measles IgG Does Not Decline During Latent SSPE

No, measles IgG does not decline during latent SSPE—in fact, IgG levels remain dramatically elevated throughout all stages of the disease, including any latent period, with persistent elevation in both serum and CSF being a hallmark diagnostic feature. 1

Understanding the Immunologic Profile in SSPE

The term "latent SSPE" requires clarification, as the immunologic evidence suggests ongoing viral activity even during clinically silent periods:

IgG Remains Persistently Elevated

• Measles-specific IgG antibodies remain dramatically elevated in both serum and CSF throughout all stages of SSPE, regardless of clinical disease stage. 1, 2
• The CSF/serum measles antibody index remains ≥1.5, confirming continuous intrathecal synthesis of IgG, which indicates local CNS antibody production rather than passive leakage from serum. 1, 3
• This persistent elevation of IgG with intrathecal synthesis has 100% sensitivity and 93.3% specificity for SSPE diagnosis. 1, 2

The "Latency Period" Is Immunologically Active

• While there is a clinical latency period of typically 2-10 years (sometimes as short as 4 months) between acute measles infection and SSPE symptom onset, this period is characterized by persistent CNS viral replication, not true immunologic quiescence. 1, 4
• The presence of persistent measles-specific IgM in both serum and CSF—often higher in CSF than serum—indicates ongoing immune stimulation from continuous CNS viral replication throughout this "latent" period. 1, 5
• This persistent IgM is highly abnormal, as IgM normally becomes completely undetectable within 30-60 days after acute measles infection. 1, 3

Diagnostic Implications

What You Actually See in SSPE

• All SSPE patients maintain detectable measles-specific IgM antibodies in serum regardless of disease stage—a finding that is 100% sensitive and pathognomonic for ongoing viral activity. 1
• The combination of persistent IgM, dramatically elevated IgG, and CSF/serum measles antibody index ≥1.5 has 100% sensitivity and 93.3% specificity for SSPE diagnosis. 1, 2
• Oligoclonal bands specific to measles virus proteins are detectable by immunoblotting in CSF, further confirming ongoing immune stimulation. 1

Critical Distinction from Other Conditions

• SSPE shows an isolated, extremely strong measles-only antibody response, distinguishing it from multiple sclerosis with MRZ reaction, which demonstrates intrathecal synthesis against at least 2 of 3 viral agents (measles, rubella, zoster). 1, 3
• In acute measles reinfection, patients show high-avidity IgG with IgM positivity but a normal CSF/serum index, whereas SSPE shows extremely high titers with an elevated CSF/serum index ≥1.5. 1

Clinical Context and Mechanism

Why IgG Stays Elevated

• The persistent elevation of both IgM and IgG reflects ongoing immune stimulation from continuous CNS viral replication, where the defective measles virus establishes true persistent infection in neurons and spreads trans-synaptically. 1, 2, 5
• The continuing release of measles antigen in SSPE prevents the normal shut-off of IgM synthesis and maintains elevated IgG production. 5
• This represents active viral persistence in the CNS, not acute infection, reinfection, or true immunologic latency. 2

Important Caveats

• During the initial acute measles infection, IgM appears 1-2 days after rash onset, peaks at 7-10 days, and disappears within 30-60 days, while IgG develops and persists at normal protective levels. 1, 3
• The reappearance and persistence of IgM years after the initial measles infection, combined with dramatically elevated IgG, is the key immunologic signature that distinguishes SSPE from normal post-measles immunity. 1, 5
• The mean incubation period between measles infection and SSPE symptom onset is approximately 9.6 years, though recent reports suggest this latency period may be decreasing. 4, 6