Does IgM (Immunoglobulin M) disappear during the latent phase of Subacute Sclerosing Panencephalitis (SSPE)?

IgM Antibodies in SSPE: Persistence Throughout Disease Course

No, IgM does not disappear during the latent phase of SSPE—measles-specific IgM antibodies persist throughout all stages of the disease, including early latent phases, which is a unique diagnostic feature distinguishing SSPE from acute measles infection. 1

Diagnostic Significance of Persistent IgM

The continuing presence of measles-specific IgM in SSPE represents a fundamental departure from typical viral infection patterns and serves as a critical diagnostic marker:

• All SSPE patients maintain high titers of anti-measles IgM antibodies in both serum and CSF regardless of disease stage, including early, middle, and late phases 1
• The diagnostic triad for SSPE specifically includes persistent measles IgM in serum/CSF as one of three essential criteria, with 100% sensitivity and 93.3% specificity when combined with elevated CSF/serum measles antibody index ≥1.5 and elevated measles-specific IgG 2
• In 35% of SSPE cases, the specific IgM response is more pronounced in CSF than in serum, suggesting active IgM production within the central nervous system itself 1

Mechanistic Explanation

The persistent IgM response in SSPE reflects ongoing viral antigen release rather than a typical immune response:

• The continuing release of measles antigen from persistent defective virus in the CNS prevents the normal shut-off of IgM synthesis that would occur after acute infection resolution 1
• Detection of virus-specific IgM antibodies in CSF of patients with chronic CNS diseases indicates viral persistence, making this a pathognomonic feature of SSPE 1
• IgM levels remain persistently elevated alongside IgG and IgA, indicating ongoing infection rather than past exposure 3

Contrast with Acute Measles

This persistent IgM pattern sharply distinguishes SSPE from acute measles infection:

• In acute measles, IgM becomes detectable 1-2 days after rash onset, peaks at 7 days, and becomes undetectable within 30-60 days, whereas SSPE maintains IgM indefinitely 2
• The absence of IgM disappearance is what differentiates chronic SSPE from resolved acute measles 2

Clinical Implications for Diagnosis

When evaluating suspected SSPE, the persistence of IgM provides critical diagnostic information:

• Obtain simultaneous serum and CSF samples for measles-specific IgM and IgG measurement as the first-line diagnostic approach 2
• Calculate the CSF/serum measles antibody index, with values ≥1.5 confirming intrathecal synthesis 2
• Do not confuse SSPE's isolated, extremely strong measles antibody response with the MRZ reaction (measles, rubella, zoster) seen in multiple sclerosis, which shows intrathecal synthesis against at least two of three viral agents 2

Progressive Immunoglobulin Patterns

While IgM persists, other immunoglobulin patterns evolve with disease progression:

• Serum IgG and IgA levels progressively increase with clinical stage, correlating with the progressive nature of the illness 3
• CSF IgG progressively increases with clinical stage without corresponding rises in measles antibody titer, suggesting antigenic determinants beyond those routinely tested contribute to CSF IgG production 3
• The ratio of CSF to serum IgG increases with disease advancement, indicating local IgG synthesis within the CNS 3