Differential isoform profiles of α₂-macroglobulin from plasma of patients with chronic-progressive or relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a human neurological disease for which no clinically useful marker has been identified in blood. This study examined α₂-macroglobulin (α_2M) from the plasma of six patients with chronic-progressive MS and six with relapsing-remitting disease. The α₂M trypsin-binding activity in the plasma from both groups of patients did not differ from normal controls. However, after column isoelectric focusing, consistently less α₂M activity was recovered from the MS samples: those from the chronic-progressive and relapsing-remitting disease groups were an average of 43% and 68%, respectively, of controls. The number and isoelectric point (pI) values of the isoforms of the α₂M from patients with chronicprogressive disease were similar to controls. The average pI of the major form for both groups was 6.6. By contrast, the average pI of the major form from the patients with relapsing-remitting MS was significantly elevated to 7.1, and this group displayed a significantly higher percentage of total recovered activity above pH 7.0. In eleven of the twelve cases examined, the pI of the major form of α₂M correctly correlated with the clinical status of the patient. The original clinical diagnosis of the patients was reassessed by a 9-year retrospective interview which verified that 9 of the 10 patients in the follow-up group retained their original clinical diagnosis. These studies demonstrate differential isoform profiles of native α₂M from MS patients with progressive versus remitting disease which may be useful in subclassifying MS patients.