Cladribine Effects on T and B Cells and T Cell Reactivity in Multiple Sclerosis.

OBJECTIVE: Cladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS), however, its mechanism of action on T and B cell subsets remains unclear. The purpose of this study was to investigate the treatment effects of cladribine on the peripheral pool of T and B cells subsets and reactivity toward central nervous system (CNS) antigens. METHODS: In this cross-sectional exploratory study, frequencies and absolute counts of peripheral T and B cell subsets and B cell cytokine production from untreated patients with relapsing-remitting MS (RRMS) and patients treated with cladribine for 1 year were measured using flow cytometry. Autoreactivity was assessed using a FluoroSpot assay. RESULTS: We found that 1 year after initiation of cladribine treatment, a lower number of CD4+ T cells was persisting whereas CD19+ B cell counts were normalized compared to untreated patients with RRMS. Follicular helper T cells and their effecter subsets producing cytokines exerting distinct B cell helper activity were lower and, additionally, the peripheral B cell pool was skewed toward a naïve and anti-inflammatory phenotype. Finally, reactivity to the recently identified CNS-enriched autoantigen RAS guanyl-releasing protein 2 (RASGRP2), but not to myelin basic protein and myelin oligodendrocyte glycoprotein, was lower in cladribine-treated patients. INTERPRETATION: Together, these investigations on T and B cell subsets suggest that cladribine treatment impairs the B-T cell crosstalk and reduces their ability to mediate pathogenic effector functions. This may result in specific reduction of autoreactivity to RASGRP2 which is expressed in B cells and brain tissue. ANN NEUROL 2023;94:518-530.

Right atrial and ventricular function evaluated with speckle tracking in patients with acute pulmonary embolism.

AIMS: Assessment of right ventricular (RV) function in acute pulmonary embolism (PE) has prognostic significance. The aim of this study was to evaluate right atrium (RA) and RV myocardial damage with 2-dimensional speckle-tracking in patients with an acute central vs an acute peripheral PE. METHODS AND RESULTS: Twenty-six patients with acute PE and 10 controls were retrospectively enrolled. Right atrium and RV myocardial deformation was analyzed using speckle-tracking imaging echocardiography. Parameters were evaluated to illustrate myocardial damage in patients with a central or a peripherally located PE. Thirteen of the enrolled patients had a massive central PE, and thirteen subjects had a peripheral located PE. Baseline characteristics were not significantly different between the 3 groups besides a more elevated heart rate among patients with a central PE (P = .02) and a tendency of an increased D-dimer in this group. Right ventricular dimensions were more affected among patients with a PE. Compared with controls, segmental RV and RA strain/strain rate in the free wall was significantly reduced in patients with PE (P < .05). No difference was shown between the 2 groups of PE. CONCLUSION: This pilot study suggests that basal-/mid-segments of RA and RV free wall are more affected in patients with a PE compared with controls. Interestingly, we found no significant difference in myocardial RA and RV damage between patients with a central and a peripheral PE. We advocate that PE no matter central or peripheral is a serious condition and that a peripheral PE has to be intensively treated similar to a central PE.