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Published on: May 8, 2016
Expression of chemokine receptors in the different clinical forms of multiple sclerosis
E M Martínez-Cáceres1, C Espejo, L Brieva
1Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Abstract:
Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sderosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS However, a pattem of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.
Insights
Chemokines and their receptors are implicated in multiple sclerosis (MS) pathogenesis. While elevated chemokine receptor expression was found in MS patients, distinct patterns for each clinical form were not observed.
Area of Science:
- Neuroimmunology
- Immunology
- Cellular Biology
Background:
- Chemokines and their receptors mediate leukocyte trafficking to the central nervous system, a key process in multiple sclerosis (MS) pathogenesis.
- Distinct clinical forms of MS (relapsing-remitting, secondary progressive, and primary progressive) suggest potential differences in underlying pathogenic mechanisms.
Purpose of the Study:
- To investigate potential differences in chemokine receptor expression between various clinical forms of MS.
- To compare the membrane expression of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood cells of MS patients and healthy controls.
Main Methods:
- Flow cytometry was used to analyze the surface expression of chemokine receptors (CCR5, CXCR3, CXCR4) on peripheral blood cells (CD4+, CD8+, CD19+, CD14+).
- Levels of CXCL10 (IP-10) and CCL5 (RANTES) were measured in the cerebrospinal fluid of a subgroup of MS patients.
Main Results:
- MS patients exhibited significantly increased surface expression of CCR5 on CD4+, CD8+, CD19+, and CD14+ cells compared to healthy controls.
- An increased percentage of CXCR3 and CXCR4 was observed on CD14+ cells in MS patients.
- Elevated levels of CXCL10 and CCL5 were detected in the cerebrospinal fluid of some MS patients.
Conclusions:
- Chemokines and their receptors play a role in the pathogenesis of multiple sclerosis.
- Despite observed differences in chemokine receptor expression in MS patients, no specific pattern was identified that characterizes each distinct clinical form of the disease.
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