Related Experiment Video
Updated: Sep 30, 2026
A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Differential isoform profiles of alpha 2-macroglobulin from plasma of patients with chronic-progressive or
1Department of Pediatrics, University of California, Orange 92668.
Abstract:
Multiple sclerosis (MS) is a human neurological disease for which no clinically useful marker has been identified in blood. This study examined alpha 2-macroglobulin (alpha 2M) from the plasma of six patients with chronic-progressive MS and six with relapsing-remitting disease. The alpha 2M trypsin-binding activity in the plasma from both groups of patients did not differ from normal controls. However, after column isoelectric focusing, consistently less alpha 2M 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 alpha 2M from patients with chronic-progressive 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 alpha 2M 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 alpha 2M from MS patients with progressive versus remitting disease which may be useful in subclassifying MS patients.
Insights
Researchers found differences in alpha 2-macroglobulin (alpha 2M) isoforms in multiple sclerosis (MS) patients. These distinct profiles may help classify MS disease subtypes, offering potential new diagnostic markers for this neurological condition.
Area of Science:
- Biochemistry
- Neurology
- Immunology
Background:
- Multiple sclerosis (MS) is a debilitating neurological disease lacking specific blood biomarkers.
- Alpha 2-macroglobulin (alpha 2M) is a key plasma protein involved in various biological processes.
Purpose of the Study:
- To investigate alpha 2-macroglobulin (alpha 2M) isoform profiles in patients with different forms of multiple sclerosis (MS).
- To determine if alpha 2M isoform analysis can serve as a clinically useful marker for MS subclassification.
Main Methods:
- Plasma samples from chronic-progressive MS, relapsing-remitting MS, and control groups were analyzed.
- Column isoelectric focusing was used to separate and quantify alpha 2M isoforms.
- Isoelectric point (pI) values and recovered activity of alpha 2M isoforms were measured.
Main Results:
- Total alpha 2M trypsin-binding activity did not differ between MS patients and controls.
- Significantly lower alpha 2M activity was recovered from MS patient plasma post-isoelectric focusing.
- Patients with relapsing-remitting MS showed an elevated average pI (7.1) for the major alpha 2M isoform compared to controls (6.6).
- The pI of the major alpha 2M isoform correlated with clinical status in 11 out of 12 patients.
Conclusions:
- Differential alpha 2M isoform profiles exist between progressive and remitting MS subtypes.
- Alpha 2M isoform analysis shows promise as a potential biomarker for subclassifying MS patients.
- Further research is warranted to validate alpha 2M as a diagnostic tool for multiple sclerosis.
