Are the genes associated with subacute sclerosing panencephalitis (SSPE) found in the host?

Host Genetic Factors in SSPE

Yes, the genes associated with SSPE susceptibility are host (human) genes, not viral genes—these are polymorphisms in the patient's own immune system genes that affect their ability to clear the measles virus from the central nervous system. 1

Understanding the Genetic Component

The genetic factors relevant to SSPE are host genetic variations that contribute to disease susceptibility and severity, not genes carried by the measles virus itself. 1 An individual's genetic makeup significantly influences variation in infectious disease susceptibility and severity, though risk alleles for infectious encephalitis have only been identified in a handful of cases. 1

Specific Host Genes Implicated in SSPE

Immune Regulatory Genes

PD-1 (Programmed Cell Death Protein 1):

• The PD-1 gene polymorphism at rs2227982 shows significant association with SSPE susceptibility. 2, 3
• The GCG(C) haplotype containing the -606G allele is significantly more frequent in SSPE patients in both Japanese and Filipino populations. 3
• This -606G allele demonstrates higher promoter activity and increased PD-1 expression levels in SSPE patients compared to controls. 3
• The T allele frequency at PD-1.9 polymorphism was significantly lower in SSPE patients (2.8%) versus controls (10.9%), suggesting protective effects. 2

Interleukin-4 (IL-4):

• The T allele at position -589 in the IL-4 promoter region shows significant association with SSPE (p=0.03). 4
• This polymorphism increases IL-4 synthesis, shifting toward a Th2 immune response. 4
• When combined with IRF-1 allele 1, the genotype combination frequency is much higher in SSPE patients (47.7%) versus controls (22.0%, p=0.003). 4

Interleukin-18 (IL-18):

• The AA genotype at position -607 is significantly more frequent in SSPE patients (p<0.001, OR: 5.76). 5
• The C allele at position -137 shows significantly higher frequency in patients (p=0.002, OR: 2.72). 5
• The CA haplotype demonstrates significantly elevated frequency in SSPE patients (p<0.001, OR: 3.99). 5

Interleukin-2 (IL-2):

• The GG genotype at position -330 shows lower frequency in SSPE patients (p=0.03, OR: 0.4). 6
• The TG haplotype (-330+160) is more frequent in patients (p=0.005, OR: 1.8). 6

Interleukin-12 (IL-12):

• The IL12B C allele (rs3213113) frequency is higher in SSPE patients (p=0.04, OR: 1.6). 6
• The CC genotype shows increased frequency in patients (p=0.03, OR: 3.2). 6

Clinical Implications

Why This Matters

These host genetic polymorphisms impair the ability of the patient's immune cells to eradicate the measles virus, allowing persistent infection in the central nervous system. 2, 4 The genes primarily affect:

• T lymphocyte function and regulation (PD-1 as a negative immune regulator). 2, 3
• Cytokine balance between Th1 and Th2 responses (IL-4, IL-2, IL-12, IL-18). 4, 5, 6
• Interferon-mediated antiviral responses (IRF-1 interaction). 4

Prevention Remains Key

Measles vaccination is the only effective prevention strategy for SSPE, as recommended by the CDC, and has led to near elimination of cases in countries with high vaccination coverage. 7, 8 The vaccine does not increase SSPE risk—the disease results from natural measles infection, not vaccination. 7

Important Caveats

• No single pathogenic mechanism that definitively predisposes to SSPE has been determined. 2
• These genetic associations require confirmation in additional populations beyond Japanese, Filipino, and Turkish cohorts. 2, 3, 4, 5, 6
• The genetic contribution represents susceptibility factors, not deterministic causes—most individuals with these polymorphisms never develop SSPE even after measles infection. 1