Reconstitution of the peripheral immune repertoire following withdrawal of fingolimod.

Background: Following fingolimod cessation, immune reconstitution or lack thereof may have consequences for disease rebound or safety of commencing alternative therapies.

Objective: To examine the degree and profile of peripheral blood lymphocyte reconstitution following fingolimod withdrawal.

Methods: Total lymphocyte counts (TLC) and CD4+/CD8+ T-cell counts were measured in 18 multiple sclerosis (MS) patients pre-treatment, on fingolimod, and up to 8-9 months post-cessation.

Naive CD4 T-cell activation identifies MS patients having rapid transition to progressive MS.

Objective: Our objective was to determine whether altered naive CD4 T-cell biology contributes to development of disease progression in secondary progressive multiple sclerosis (SPMS).

Methods: We compared the naive CD4 T-cell gene expression profiles of 19 patients with SPMS and 14 healthy controls (HCs) using a whole-genome microarray approach. We analyzed surface protein expression of critical genes by flow cytometry after T-cell receptor (TCR) stimulation of naive CD4 T cells isolated from HCs and patients with SPMS.

Reduced thymic output and peripheral naïve CD4 T-cell alterations in primary progressive multiple sclerosis (PPMS).

We compared naïve CD4 and CD8 T-cell homeostasis in primary progressive multiple sclerosis (PPMS), relapsing-remitting MS (RRMS) and controls. Quantitation of signal joint T-cell receptor (TCR) excision circles (sjTRECs) and quantitative estimates of daily thymic export confirm our previous report of reduced thymic output in RRMS and demonstrate reduced thymic output in PPMS. In PPMS, the decreasing % CD31+ naïve CD4 T-cells but constant sjTRECs and constant naïve CD4 T-cell numbers with age, together with increased Bcl-2 expression suggest increased TCR signaling with increased naïve T-cell survival.