GM2A antibody targets the GM2 activator protein, a crucial cofactor in the lysosomal degradation of GM2 gangliosides. GM2 gangliosides are sphingolipids abundant in neuronal cell membranes, and their metabolism relies on the GM2 activator protein (GM2AP) to solubilize GM2 and present it to β-hexosaminidase A for cleavage. Dysregulation of this process, due to genetic mutations in GM2AP, underlies the rare lysosomal storage disorder AB-variant GM2 gangliosidosis.
Anti-GM2A antibodies are primarily associated with autoimmune neuropathy, particularly Guillain-Barré syndrome (GBS) and its variants. These autoantibodies may interfere with GM2 ganglioside metabolism or directly target neuronal structures, contributing to immune-mediated nerve damage. While anti-GM1 or anti-GQ1b antibodies are more commonly linked to specific GBS subtypes (e.g., acute motor axonal neuropathy or Miller Fisher syndrome), GM2A antibodies are less frequently detected and their clinical significance remains under investigation.
Detection typically involves ELISA or immunoblotting using purified GM2AP. Research suggests these antibodies may correlate with specific neurological symptoms, though their role as biomarkers or pathogenic drivers requires further validation. Current studies focus on clarifying their diagnostic utility and exploring potential cross-reactivity with structurally related gangliosides in autoimmune neuropathy.