Analysis of IgG responses to Sarcocystis neurona in horses with equine protozoal myeloencephalitis (EPM) suggests a Th1-biased immune response.

Overview

• This research investigates the immune responses in horses infected with Sarcocystis neurona, the parasite causing equine protozoal myeloencephalitis (EPM), focusing on IgG antibody subtypes to understand immune mechanisms linked to disease manifestation.

Background

• Equine Protozoal Myeloencephalitis (EPM): A significant neurological disease in horses in the Americas, caused by the parasite Sarcocystis neurona.
• Infection vs Disease: Although many horses are infected (high seroprevalence), less than 1% develop clinical EPM, highlighting that infection does not always lead to disease.
• Diagnostic Challenge: Serum antibodies indicate exposure but cannot reliably diagnose active disease before death (antemortem diagnosis is difficult).
• Importance of Immunity: The immune system’s role in the development or prevention of EPM is not fully understood but may be key to why only some infected horses develop symptoms.

Immunoglobulin G (IgG) Subisotypes and Immune Response

• IgG in Horses: The major antibody class in horse blood serum, with four subisotypes categorized as:
• IgG1/2 (IgGa) and IgG4/7 (IgGb): Indicative of a Th1-type immune response, which is cell-mediated and important for fighting intracellular pathogens like parasites.
• IgG3/5 (IgG(T)) and IgG6 (IgGc): Indicative of a Th2-type immune response, which is more humoral (involving antibody production).

Hypothesis

• The authors proposed that EPM results from an abnormal or unbalanced immune response, which might be detected by measuring specific IgG subisotypes.

Methods

• A modified Enzyme-Linked Immunosorbent Assay (ELISA) was developed to quantify the levels of S. neurona-specific IgG subisotypes 1/2, 3/5, and 4/7.
• Baseline concentrations and standard curves were established using serum samples from 21 healthy horses.
• IgG subisotype levels were then measured in:
• Serum and cerebrospinal fluid (CSF) from 93 horses with clinical EPM (infected diseased group).
• Serum and CSF from 116 infected but clinically normal horses (infected normal group).

Results

• The concentration of IgG3/5 (Th2-related) and the ratio of IgG1/2 (Th1-related) to IgG3/5 differed significantly between diseased and normal horses.
• This suggests that horses with EPM have an immune response skewed toward a Th1-type, cell-mediated immunity profile.
• Despite this difference, the variability was not pronounced enough to use these subisotype measurements alone to develop a reliable blood test for EPM diagnosis.

Implications

• The data support the idea that the type of immune response to S. neurona infection affects disease outcome.
• A Th1-biased response might contribute to the development or progression of clinical EPM.
• Understanding immune response patterns could guide future therapeutic strategies or improve diagnostics if combined with other markers.
• However, current serum IgG subisotype assays are insufficient by themselves for definitive antemortem diagnosis of EPM.