Abstract Details

Title Biomarker Value of B Cell-based CCL4L2 in Differential Diagnosis of Autoimmune Inflammatory Demyelinating Disorders

Topic Multiple Sclerosis

Presentation(s) P8 - Poster Session 8 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-008

Objective Due to growing significance of B cells in multiple sclerosis (MS) pathogenesis, we investigated a B cell-based biomarker that could differentiate (MS) with predominant involvement of the spinal cord and optic nerves (MS-SCON) and neuromyelitis optica spectrum disorder (NMOSD).

Background MS may occasionally present with predominant involvement of the spinal cord and optic nerves (MS-SCON). This subgroup of MS may mimic NMOSD and thus a biomarker that differentiates MS-SCON and NMOSD may prove useful.

Design/Methods Patients with relapsing remitting MS (RRMS, n=23), recurrent inflammatory optic neuritis (n=15), MS-SCON (n=17), NMOSD (n=9) and 21 healthy controls were enrolled. B cells were isolated from peripheral blood by magnetic-activated cell sorting and microarray analysis was performed with Agilent Human 8X60K Oligo Microarray. Differentially expressed genes (DEGS) were determined and functional analysis (gene ontology and pathway analysis) was done using the DAVID database. Validation of microarray results was accomplished by real-time PCR. Serum levels of CCL4L2 (the most significantly elevated DEG in MS-SCON) were measured by ELISA. Pathogenic significance of this gene was investigated through shRNA-mediated gene suppression in the proteolipid protein-induced experimental autoimmune myelitis (EAE) model.

Results Microarray and PCR analysis determined CCL4L2, CSF3R, CCL20 and IL-18R as the most significantly elevated genes in MS-SCON as compared to other patient and healthy controls. By contrast serum levels of CCL4L2 were identical among groups indicating that only B cell-based CCL4L2 could be used as a biomarker. shRNA-dependent suppression of CCL4L2 did not ameliorate the clinical and pathological features of the EAE model.

Conclusions Our findings suggest that CCL4L2 does not have a functional significance in MS physiopathology. However, B cell-based expression level of CCL4L2 may serve as a diagnostic biomarker for differentiation of MS-SCON and NMOSD.

Authors/Disclosures
Erdem Tuzun PRESENTER	Erdem Tuzun has nothing to disclose.
Recai Turkoglu	Recai Turkoglu has nothing to disclose.
Gizem Koral (Istanbul University)	No disclosure on file
Elif Is (Istanbul University)	No disclosure on file
Zerrin Karaaslan, MD, PhD	Dr. Karaaslan has nothing to disclose.
Hande Yuceer Korkmaz	No disclosure on file
Tuncay Gunduz, MD (ISTANBUL UNIVERSITESI NOROLOJI SERVISI)	The institution of Dr. Gunduz has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Pharmaceuticals. Dr. Gunduz has received research support from Turkish Neuroimmunology Society.
Murat Kurtuncu, MD (Istanbul University)	Dr. Kurtuncu has nothing to disclose.
Cem Kucukali	No disclosure on file
Vuslat Yilmaz	No disclosure on file

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