Macrophage procoagulant activity as a measure of cell-mediated immunity to P2 protein of peripheral nerves in the Guillain-Barré syndrome

Abstract

Cell-mediated and humoral immunity to purified nerve proteins has been assessed in GBS patients and compared with that of patients with other neurological diseases and healthy controls. A strong and specific cell-mediated response to the neuritogenic basic protein P2 occurred in 13/16 GBS patients tested. Extremely low levels of P2 (0.01 micrograms/culture) induced monocyte/macrophage procoagulant activity (MPCA) on peripheral blood mononuclear cells (PBM) from GBS patients (P = 0.007) whereas higher concentrations (2 micrograms/culture) of myelin basic protein (MBP) and sciatic nerve myelin (SNM) were required to stimulate similar levels of activity. These concentrations of nerve antigens failed to induce significant MPCA on peripheral blood mononuclear cells of patients with other neuropathies or healthy controls. Lipopolysaccharide, a non-specific stimulant of macrophage procoagulant activity, induced similar procoagulant levels on PBM from each group. The MPCA assay was a sensitive, quantitative and specific indicator of cell-mediated immunity to the neuritogenic peptide, P2 in GBS patients. Serum antibodies to P2, P0 and SNM were detected by a sensitive solid-phase radioimmunoassay. Naturally occurring antibodies to peripheral nerve antigens were observed in sera of healthy subjects and these levels were not significantly different from patients with GBS or those with other neuropathies. Our results indicate that the autoimmune cell-mediated response to the neuritogenic peptide P2 plays a major role in the pathogenesis of GBS.