Αναζήτηση αυτού του ιστολογίου

Τρίτη 1 Δεκεμβρίου 2020

Differential Effects of Fingolimod and Natalizumab on B Cell Repertoires in Multiple Sclerosis Patients

xlomafota.13 shared this article with you from Inoreader

13311.jpg

Abstract

Natalizumab and fingolimod are effective multiple sclerosis (MS) therapies that disrupt lymphocyte migration but have differential effects on B cell maturation and trafficking. We investigated their effects on peripheral blood (PB) and cerebrospinal fluid (CSF) B cell repertoires using next-generation deep sequencing. Paired CSF and PB B cell subsets (naïve, CD27+ memory, and CD27IgD double-negative B cells and plasmablasts) were collected by applying flow cytometry at baseline and after 6 months of treatment and their respective heavy-chain variable region repertoires assessed by Illumina MiSeq. Treatment with fingolimod contracted, whereas natalizumab expanded circulating PB B cells. CSF B cell numbers remained stable following fingolimod treatment but decreased with natalizumab therapy. Clonal overlap between CSF and PB B cells was reduced with natalizumab treatment but remained stable with fingolimod therapy. Linea ge analyses of pre- and posttreatment CSF B cell repertoires revealed large, clonally expanded B cell clusters in natalizumab-treated MS patients but no intrathecal clonal expansion following fingolimod therapy. Our findings suggest that natalizumab diminishes the exchange of peripheral and intrathecal B cells without impacting intrathecal clonal expansion. In contrast, fingolimod treatment fails to alter blood–brain barrier B cell exchange but diminishes intrathecal clonal expansion. Sphingosine-1 phosphate receptor inhibition may alter intrathecal B cell biology in MS.

View on the web

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.