Correlation between clinical symptoms and peripheral immune response in HAM/TSP

Area of Science:

• Immunology
• Virology
• Neuroscience

Background:

• Human T-lymphotropic virus type 1 (HTLV-1) primarily infects CD4+ T cells, serving as the main viral reservoir.
• While most HTLV-1 infections are asymptomatic, 2-3% of individuals develop HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis) or Adult T-cell leukemia.
• HAM/TSP is a chronic central nervous system inflammatory disease marked by persistent myelopathic symptoms, with altered cytokine levels (IFN-γ, TNF-α) linked to tissue injury.

Purpose of the Study:

• To compare the gene expression of IFN-γ, IL-4, and IL-10 in asymptomatic HTLV-1 infected patients versus those with HAM/TSP.
• To correlate the gene expression levels of these cytokines with the clinical symptoms of HAM/TSP.

Main Methods:

• Gene expression of IFN-γ, IL-4, and IL-10 was measured using Real-Time PCR in 28 subjects (20 asymptomatic, 8 HAM/TSP).
• Clinical symptoms, including spasticity (Modified Ashworth Scale) and need for walking aids, were assessed.

Main Results:

• All patients exhibited high IFN-γ gene expression, notably higher in the HAM/TSP group.
• A significant positive correlation was found between IFN-γ gene expression and the degree of walking aid required.
• IFN-γ gene expression was significantly higher in wheelchair users compared to non-wheelchair users; no associations were found for IL-4 and IL-10.

Conclusions:

• HAM/TSP patients demonstrate elevated IFN-γ gene expression compared to asymptomatic HTLV-1 carriers.
• IFN-γ gene expression strongly correlates with disease severity, specifically the need for mobility assistance in HAM/TSP patients.