Adhesion Molecules in Multiple Sclerosis

Abstract

Up-regulated adhesion molecules in blood and CSF indicate sustained potential for inflammation in the CNS throughout the clinical spectrum of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.

MicroRNA‑155 modulation of CD8+ T‑cell activity personalizes response to disease‑modifying therapies of patients with relapsing‑remitting multiple sclerosis

“…Moreover, upregulation of ICAM1, ITGB2, perforin, and granzyme B was observed in all patients with RRMS compared to healthy controls (20). This upregulation of ICAM1 and ITGB2 [β sub-unit of lymphocyte function-associated antigen 1 (LFA-1)] is consistent with previous results showing overexpression of ICAM1 and LFA-1 on mononuclear cells from the blood of patients with RRMS compared to controls (35). Another interesting study by Fujii et al studied the levels of cytotoxic proteins perforin and granzyme B in patients administered fingolimod and found a significant increase in perforin and granzyme B expression in both relapse-free and relapsing patients with higher overexpression in the latter compared to the healthy controls (36).…”

MicroRNA‑155 modulation of CD8+ T‑cell activity personalizes response to disease‑modifying therapies of patients with relapsing‑remitting multiple sclerosis

“…Moreover, upregulation of ICAM1, ITGB2, perforin, and granzyme B was observed in all patients with RRMS compared to healthy controls (20). This upregulation of ICAM1 and ITGB2 [β sub-unit of lymphocyte function-associated antigen 1 (LFA-1)] is consistent with previous results showing overexpression of ICAM1 and LFA-1 on mononuclear cells from the blood of patients with RRMS compared to controls (35). Another interesting study by Fujii et al studied the levels of cytotoxic proteins perforin and granzyme B in patients administered fingolimod and found a significant increase in perforin and granzyme B expression in both relapse-free and relapsing patients with higher overexpression in the latter compared to the healthy controls (36).…”

Stage-Specific Gene Expression Profiles in Multiple Sclerosis Cortical Lesions Identified via Spatial Transcriptomics

“…20,21 Moreover, the increased expression of T and B lymphocyte-related genes in the EAL sample, like CD2, CD3D, IGHG4, and IGKC, together with the upregulation of genes involved in cell adhesion and migration like VCAM1, ITGAL, SELL, or chemokines like CCL5, suggests ongoing immune cell in ltration across the BBB. [22][23][24][25][26] The enrichment of BPs related to leukocyte proliferation, cytokine production, and chemotaxis highlights the dynamic interplay between innate and adaptive immune responses in early lesion formation, 22 and aligns with previous studies demonstrating that chemokines play a pivotal role in recruiting peripheral immune cells to the CNS, where they contribute to in ammation and tissue damage. 24 The disruption of BBB integrity in the EAL sample may be re ected by the enrichment of biological processes like "cell surface interactions at the vascular wall" and "platelet degranulation", that together with the detection of RHO, RAC1 and CDC42 GTPase cycles pints to cytoskeletal remodeling events necessary for immune cell motility and tissue in ltration.…”

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

“…Therefore, endothelial activation can be used as a surrogate biomarker for multiple sclerosis activity. In line with this hypothesis, expression of adhesion molecules expression is upregulated in the CNS of multiple sclerosis patients 98 and their plasma levels correlate with the activity of the disease 99 , although, at the individual level, these biomarkers are of insufficient clinical utility. Furthermore, one of the most effective treatments for multiple sclerosis is a monoclonal antibody directed against VLA-4 (natalizumab) that prevents its interaction with VCAM-1, thereby blocking lymphocyte diapedesis and significantly reducing disease activity 67 .…”

MicroRNA‑155 modulation of CD8+ T‑cell activity personalizes response to disease‑modifying therapies of patients with relapsing‑remitting multiple sclerosis

“…Moreover, upregulation of ICAM1, ITGB2, perforin, and granzyme B was observed in all patients with RRMS compared to healthy controls (20). This upregulation of ICAM1 and ITGB2 [β sub-unit of lymphocyte function-associated antigen 1 (LFA-1)] is consistent with previous results showing overexpression of ICAM1 and LFA-1 on mononuclear cells from the blood of patients with RRMS compared to controls (35). Another interesting study by Fujii et al studied the levels of cytotoxic proteins perforin and granzyme B in patients administered fingolimod and found a significant increase in perforin and granzyme B expression in both relapse-free and relapsing patients with higher overexpression in the latter compared to the healthy controls (36).…”

Stage-Specific Gene Expression Profiles in Multiple Sclerosis Cortical Lesions Identified via Spatial Transcriptomics

“…20,21 Moreover, the increased expression of T and B lymphocyte-related genes in the EAL sample, like CD2, CD3D, IGHG4, and IGKC, together with the upregulation of genes involved in cell adhesion and migration like VCAM1, ITGAL, SELL, or chemokines like CCL5, suggests ongoing immune cell in ltration across the BBB. [22][23][24][25][26] The enrichment of BPs related to leukocyte proliferation, cytokine production, and chemotaxis highlights the dynamic interplay between innate and adaptive immune responses in early lesion formation, 22 and aligns with previous studies demonstrating that chemokines play a pivotal role in recruiting peripheral immune cells to the CNS, where they contribute to in ammation and tissue damage. 24 The disruption of BBB integrity in the EAL sample may be re ected by the enrichment of biological processes like "cell surface interactions at the vascular wall" and "platelet degranulation", that together with the detection of RHO, RAC1 and CDC42 GTPase cycles pints to cytoskeletal remodeling events necessary for immune cell motility and tissue in ltration.…”

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

“…Therefore, endothelial activation can be used as a surrogate biomarker for multiple sclerosis activity. In line with this hypothesis, expression of adhesion molecules expression is upregulated in the CNS of multiple sclerosis patients 98 and their plasma levels correlate with the activity of the disease 99 , although, at the individual level, these biomarkers are of insufficient clinical utility. Furthermore, one of the most effective treatments for multiple sclerosis is a monoclonal antibody directed against VLA-4 (natalizumab) that prevents its interaction with VCAM-1, thereby blocking lymphocyte diapedesis and significantly reducing disease activity 67 .…”

MicroRNA‑155 modulation of CD8+ T‑cell activity personalizes response to disease‑modifying therapies of patients with relapsing‑remitting multiple sclerosis

“…Moreover, upregulation of ICAM1, ITGB2, perforin, and granzyme B was observed in all patients with RRMS compared to healthy controls (20). This upregulation of ICAM1 and ITGB2 [β sub-unit of lymphocyte function-associated antigen 1 (LFA-1)] is consistent with previous results showing overexpression of ICAM1 and LFA-1 on mononuclear cells from the blood of patients with RRMS compared to controls (35). Another interesting study by Fujii et al studied the levels of cytotoxic proteins perforin and granzyme B in patients administered fingolimod and found a significant increase in perforin and granzyme B expression in both relapse-free and relapsing patients with higher overexpression in the latter compared to the healthy controls (36).…”

Stage-Specific Gene Expression Profiles in Multiple Sclerosis Cortical Lesions Identified via Spatial Transcriptomics

“…20,21 Moreover, the increased expression of T and B lymphocyte-related genes in the EAL sample, like CD2, CD3D, IGHG4, and IGKC, together with the upregulation of genes involved in cell adhesion and migration like VCAM1, ITGAL, SELL, or chemokines like CCL5, suggests ongoing immune cell in ltration across the BBB. [22][23][24][25][26] The enrichment of BPs related to leukocyte proliferation, cytokine production, and chemotaxis highlights the dynamic interplay between innate and adaptive immune responses in early lesion formation, 22 and aligns with previous studies demonstrating that chemokines play a pivotal role in recruiting peripheral immune cells to the CNS, where they contribute to in ammation and tissue damage. 24 The disruption of BBB integrity in the EAL sample may be re ected by the enrichment of biological processes like "cell surface interactions at the vascular wall" and "platelet degranulation", that together with the detection of RHO, RAC1 and CDC42 GTPase cycles pints to cytoskeletal remodeling events necessary for immune cell motility and tissue in ltration.…”

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

“…Therefore, endothelial activation can be used as a surrogate biomarker for multiple sclerosis activity. In line with this hypothesis, expression of adhesion molecules expression is upregulated in the CNS of multiple sclerosis patients 98 and their plasma levels correlate with the activity of the disease 99 , although, at the individual level, these biomarkers are of insufficient clinical utility. Furthermore, one of the most effective treatments for multiple sclerosis is a monoclonal antibody directed against VLA-4 (natalizumab) that prevents its interaction with VCAM-1, thereby blocking lymphocyte diapedesis and significantly reducing disease activity 67 .…”