Contributions
Abstract: P858
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Optic neuritis (ON) is an inflammatory optic neuropathy, which causes demyelination and axonal injury. The predilection of the optic nerve in multiple sclerosis (MS) may be explained by regional differences in blood-brain-barrier (BBB) permeability. Microfibrillar-associated protein 4 (MFAP4) is located to the vascular extracellular matrix and has binding capacity for integrin alphaVbeta3, which is an essential matrix receptor of the BBB. Soluble MFAP4 is previously suggested as a biomarker of increased tissue breakdown in vascular disease.
Objective: To measure levels of MFAP4 in serum and cerebrospinal fluid (CSF) of ON patients. Furthermore, to determine if MFAP4 is expressed in the vasculature of the human optic nerve.
Methods: We identified 36 patients with acute ON from a population-based prospective cohort between 2014 and 2016 with a one-year follow-up. Serum and CSF samples were obtained in the acute stage of ON at a median interval from onset of symptoms of 13 days (range 2-59), in all cases prior to steroid treatment. The patients had a female:male ratio of 1.8:1 and a median age of 36 years (range 16-66). Overall, 12/36 patients were diagnosed with MS at onset of ON (MS-ON) and additionally 4 were diagnosed at follow-up, 20 patients remained as isolated ON (ION). Sample material from otherwise healthy individuals (n=20) acted as controls. AlphaLISA immunoassay was used to determine MFAP4 in CSF and serum. One-way ANOVA followed by Fisher's LSD test was used for comparisons. For histology, paraffin embedded human optic nerve tissuesections were immunostained for MFAP4.
Results: CSF levels of MFAP4 were significantly lower in ON patients compared to healthy controls (p=0.0053). Stratification based on the follow-up diagnosis showed lower levels in CSF in MS-ON (p = 0.0092) as well as ION (p = 0.0178) patients compared to healthy controls. Immunohistochemical analysis demonstrated that the MFAP4 protein is located in the vascular extracellular matrix (ECM) of the human optic nerve.
Conclusions: MFAP4 is a protein in the optic nerve vascular ECM and is altered or downregulated in CSF in acute ON. These findings suggest that MFAP4 has pathophysiological importance.
Disclosure: MN Olesen: Received support for congress participation from Merck
K Soelberg: Received support for congress participation from Merck
S Heegaard: Nothing to disclose
ST Lillevang: Nothing to disclose
U Holmskov: Nothing to disclose
GL Sorensen: Nothing to disclose
N Asgari: Received support for congress participation from Merck
Abstract: P858
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Optic neuritis (ON) is an inflammatory optic neuropathy, which causes demyelination and axonal injury. The predilection of the optic nerve in multiple sclerosis (MS) may be explained by regional differences in blood-brain-barrier (BBB) permeability. Microfibrillar-associated protein 4 (MFAP4) is located to the vascular extracellular matrix and has binding capacity for integrin alphaVbeta3, which is an essential matrix receptor of the BBB. Soluble MFAP4 is previously suggested as a biomarker of increased tissue breakdown in vascular disease.
Objective: To measure levels of MFAP4 in serum and cerebrospinal fluid (CSF) of ON patients. Furthermore, to determine if MFAP4 is expressed in the vasculature of the human optic nerve.
Methods: We identified 36 patients with acute ON from a population-based prospective cohort between 2014 and 2016 with a one-year follow-up. Serum and CSF samples were obtained in the acute stage of ON at a median interval from onset of symptoms of 13 days (range 2-59), in all cases prior to steroid treatment. The patients had a female:male ratio of 1.8:1 and a median age of 36 years (range 16-66). Overall, 12/36 patients were diagnosed with MS at onset of ON (MS-ON) and additionally 4 were diagnosed at follow-up, 20 patients remained as isolated ON (ION). Sample material from otherwise healthy individuals (n=20) acted as controls. AlphaLISA immunoassay was used to determine MFAP4 in CSF and serum. One-way ANOVA followed by Fisher's LSD test was used for comparisons. For histology, paraffin embedded human optic nerve tissuesections were immunostained for MFAP4.
Results: CSF levels of MFAP4 were significantly lower in ON patients compared to healthy controls (p=0.0053). Stratification based on the follow-up diagnosis showed lower levels in CSF in MS-ON (p = 0.0092) as well as ION (p = 0.0178) patients compared to healthy controls. Immunohistochemical analysis demonstrated that the MFAP4 protein is located in the vascular extracellular matrix (ECM) of the human optic nerve.
Conclusions: MFAP4 is a protein in the optic nerve vascular ECM and is altered or downregulated in CSF in acute ON. These findings suggest that MFAP4 has pathophysiological importance.
Disclosure: MN Olesen: Received support for congress participation from Merck
K Soelberg: Received support for congress participation from Merck
S Heegaard: Nothing to disclose
ST Lillevang: Nothing to disclose
U Holmskov: Nothing to disclose
GL Sorensen: Nothing to disclose
N Asgari: Received support for congress participation from Merck