Abstract Details

Title Non-Classical and Intermediate Monocytes in the Peripheral Blood and Cerebrospinal Fluid of Multiple Sclerosis Patients

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 228

Objective

Background BACKGROUND: Non-classical and intermediate monocytes, characterized by the expression of the FC gamma receptor III (CD16) have unique functional and migratory properties. Whereas classical monocytes home to the site of inflammation, CD16+ monocytes continuously patrol the peripheral vasculature and may migrate to solid organs under steady-state conditions.

Design/Methods DESIGN/METHODS: The frequency of circulating CD14+CD16- classical, CD14++CD16+ intermediate and CD14+CD16++ non-classical monocytes was assessed by flow cytometry (n=20 MS, n=42 controls). Monocyte immune phenotyping was performed on cerebrospinal fluid (CSF) from patients with MS (n=13) or non-inflammatory neurological diseases (NIND, n=32) and on brain biopsies. Differences in monocyte functions were addressed by phagocytosis, proliferation and transmigration assays.

Results RESULTS: Non-classical and intermediate monocytes expressed higher levels of costimulatory molecules and proved to be highly potent antigen-presenters that provoked a strong Th17 response to myelin antigens. Compared to controls, untreated MS patients had lower percentages of peripheral blood intermediate (4.3 +/- 0,85 % vs. 2,2 +/- 0,35%) and non-classical monocytes (6,5 +/-0,67% vs. 3,3 +/-0,48). In contrast to the low frequency in the periphery, 57,8% of CD14+ cells (+/-3,13) displayed a CD16+ phenotype in NIND patients. The percentage of CD16+ CSF monocytes was considerably lower in MS (37,67% +/-4,33) while these cells were found in MS lesions in a perivascular localization.

Conclusions CONCLUSIONS: CD16+ patrolling monocytes are highly potent antigen-presenters that gain access to CSF-filled spaces under physiological conditions where they may encounter auto-aggressive T cells. Non-classical/intermediate monocytes are reduced in the peripheral blood and CSF in MS which may indicate an aberrant composition of the monocyte pool or reflect a higher recruitment of classical monocytes. This may be of biological significance for immune responses to auto-antigens in the periphery and the immune surveillance of the CNS.

Authors/Disclosures
Anne Waschbisch (Neurologische Klinik) PRESENTER	No disclosure on file
	No disclosure on file
De-Hyung Lee, MD (Departement of Neurology, St. Josef Hospital,)	No disclosure on file
	No disclosure on file
Christine Stadelmann-Nessler	No disclosure on file
Ralf Linker (Uniklinik Erlangen)	Dr. Linker has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Linker has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. The institution of Dr. Linker has received research support from Novartis. The institution of Dr. Linker has received research support from Biogen.
Brigitte Wildemann, MD (University Hospital Heidelberg, Department of Neurology)	The institution of Dr. Wildemann has received research support from Roche. The institution of Dr. Wildemann has received research support from Novartis. The institution of Dr. Wildemann has received research support from Argenx. Dr. Wildemann has received personal compensation in the range of $500-$4,999 for serving as a Conference participant with Neuraxpharm. Dr. Wildemann has received personal compensation in the range of $0-$499 for serving as a Speaker with Roche. Dr. Wildemann has received personal compensation in the range of $0-$499 for serving as a Soeaker with Instand.

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