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Cell-mediated immune response to copolymer I in multiple sclerosis measured by the macrophage procoagulant activity
1Department of Psychology, La Trobe University, Bundoora, Victoria, Australia.
Abstract:
The macrophage/monocyte procoagulant activity (MPCA) assay, a sensitive and specific in vitro test for cell-mediated immunity, has been used to ascertain the reactivity of MS peripheral blood mononuclear cells (PBM) to copolymer I (Copl), a synthetic peptide analogue of myelin basic protein (MBP) currently being tested as a possible therapeutic agent in multiple sclerosis (MS). Because the suppressive effect of Copl is believed to lie in its possible cross-reactivity with MBP, the reactivity of PBM of MS patients to MBP was also tested. MS patients either at the stable phase of the relapsing/remitting form or with chronic progressive disease were investigated and compared with patients with other diseases and with healthy subjects. The reactivity to Copl was significantly increased in patients with chronic progressive disease but not in stable MS patients or in control subjects. No difference in reactivity to MBP between MS patients and healthy subjects was found regardless of disease status. However, in the control group comprising patients with other diseases, MBP reactivity was significantly elevated. In chronic progressive MS patients, a relationship was found between the response to Copl and that to MBP, supporting the possibility of an immunological cross-reactivity between these two antigens. There was no significant difference in reactivity to the non-specific stimulant, lipopolysaccharide, between the MS and control groups.
Insights
The macrophage/monocyte procoagulant activity (MPCA) assay revealed increased reactivity to copolymer I (Copl) in chronic progressive multiple sclerosis (MS) patients. This suggests a potential cross-reactivity between Copl and myelin basic protein (MBP) in MS.
Area of Science:
- Immunology
- Neuroscience
- Biochemistry
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Copolymer I (Copl), a synthetic peptide, is investigated as a therapeutic agent for MS due to its similarity to myelin basic protein (MBP).
- Cell-mediated immunity plays a crucial role in the pathogenesis and potential treatment of MS.
Purpose of the Study:
- To investigate the reactivity of peripheral blood mononuclear cells (PBM) from MS patients to Copl and MBP using the macrophage/monocyte procoagulant activity (MPCA) assay.
- To explore the potential immunological cross-reactivity between Copl and MBP in MS.
- To compare immune responses in MS patients (stable and chronic progressive) with healthy controls and patients with other diseases.
Main Methods:
- Utilized the macrophage/monocyte procoagulant activity (MPCA) assay, a sensitive in vitro test for cell-mediated immunity.
- Assessed the reactivity of PBM from multiple sclerosis (MS) patients and control groups to copolymer I (Copl) and myelin basic protein (MBP).
- Compared reactivity to a non-specific stimulant, lipopolysaccharide (LPS), to control for general immune cell activation.
Main Results:
- Significantly increased reactivity to Copl was observed in patients with chronic progressive MS, but not in stable MS patients or controls.
- No significant difference in reactivity to MBP was found between MS patients and healthy subjects.
- Elevated MBP reactivity was noted in the control group with other diseases, and a correlation between Copl and MBP reactivity was found in chronic progressive MS patients.
- No significant differences in lipopolysaccharide reactivity were observed between MS and control groups.
Conclusions:
- The findings suggest that copolymer I (Copl) may induce a specific immune response in chronic progressive multiple sclerosis (MS) patients.
- The observed relationship between Copl and myelin basic protein (MBP) reactivity supports the hypothesis of immunological cross-reactivity, potentially relevant to Copl's therapeutic mechanism in MS.
- The MPCA assay is a valuable tool for assessing cell-mediated immune responses in neurological diseases like MS.