Author Of 1 Presentation
P0383 - Resistance of CD11c+ B cells to anti-CD20 depletion with treatment initiation and early preferential repopulation of anti-inflammatory B cells in MS (ID 1210)
Abstract
Background
Anti-CD20 therapy is highly efficacious in limiting new disease activity in multiple sclerosis (MS), which depletes most circulating B cells and a small subset of T cells. However, relatively little is known about how anti-CD20 therapy affects T cells.
Objectives
We aimed to define phenotypic and functional profiles of B cells during depletion and early reconstitution following anti-CD20 antibody initiation.
Methods
Peripheral blood mononuclear cells (PBMC) were serially isolated and cryopreserved using strict standard operating procedures prior to treatment, early (3-4 months) and/or later (approx. 6 months). Following anti-CD20 (ocrelizumab) treatment initiation, in 18 previously treatment-naive MS patients. Functional immune phenotyping was performed in batch using multi-parametric flow cytometry panels developed and validated for use with cryopreserved PBMC.
Results
In addition to plasmablasts which, as expected, were not fully depleted, CD11c+ B cells appeared less efficiently depleted after treatment initiation. By 6 months post-treatment, B cells were partially repopulated, though to differing extents across individuals. In general, CD10+ transitional B cells (implicated as anti-inflammatory), and a subset of memory B cells, were preferentially repopulated. The repopulating B cells exhibited increased proliferation, though they expressed lower levels of activation markers and higher levels of regulatory markers. Ratios of IL-6/IL-10-producing B cells were significantly diminished in the reconstituting population, as compared to the treatment-naïve baseline.
Conclusions
The abnormal pro-inflammatory/anti-inflammatory imbalance of B cells seen in untreated MS patients appears improved in reconstituting B cells even after an initial cycle of ocrelizumab, though with a considerable degree of heterogeneity across patients. Unexpectedly, CD11c+ B cells, that have been implicated as pro-inflammatory in other systemic autoimmune diseases, appeared less susceptible to depletion. Of interest is whether a particular imbalance between CD11c+ B and other B cell subsets may underlie the infrequent episodes of disease activity observed early after treatment initiation.
Presenter Of 1 Presentation
P0383 - Resistance of CD11c+ B cells to anti-CD20 depletion with treatment initiation and early preferential repopulation of anti-inflammatory B cells in MS (ID 1210)
Abstract
Background
Anti-CD20 therapy is highly efficacious in limiting new disease activity in multiple sclerosis (MS), which depletes most circulating B cells and a small subset of T cells. However, relatively little is known about how anti-CD20 therapy affects T cells.
Objectives
We aimed to define phenotypic and functional profiles of B cells during depletion and early reconstitution following anti-CD20 antibody initiation.
Methods
Peripheral blood mononuclear cells (PBMC) were serially isolated and cryopreserved using strict standard operating procedures prior to treatment, early (3-4 months) and/or later (approx. 6 months). Following anti-CD20 (ocrelizumab) treatment initiation, in 18 previously treatment-naive MS patients. Functional immune phenotyping was performed in batch using multi-parametric flow cytometry panels developed and validated for use with cryopreserved PBMC.
Results
In addition to plasmablasts which, as expected, were not fully depleted, CD11c+ B cells appeared less efficiently depleted after treatment initiation. By 6 months post-treatment, B cells were partially repopulated, though to differing extents across individuals. In general, CD10+ transitional B cells (implicated as anti-inflammatory), and a subset of memory B cells, were preferentially repopulated. The repopulating B cells exhibited increased proliferation, though they expressed lower levels of activation markers and higher levels of regulatory markers. Ratios of IL-6/IL-10-producing B cells were significantly diminished in the reconstituting population, as compared to the treatment-naïve baseline.
Conclusions
The abnormal pro-inflammatory/anti-inflammatory imbalance of B cells seen in untreated MS patients appears improved in reconstituting B cells even after an initial cycle of ocrelizumab, though with a considerable degree of heterogeneity across patients. Unexpectedly, CD11c+ B cells, that have been implicated as pro-inflammatory in other systemic autoimmune diseases, appeared less susceptible to depletion. Of interest is whether a particular imbalance between CD11c+ B and other B cell subsets may underlie the infrequent episodes of disease activity observed early after treatment initiation.