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Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with "Inhibitor" formation.
Blood Research 2024 April 17
BACKGROUND: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19+ IgD- CD27+ /non-class-switched CD19+ IgD+ CD27+ memory B cell subsets and CD19+ CD27hi CD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients.
METHODS: This cross-sectional case-control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry.
RESULTS: The frequency of CD19+ IgD+ CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both CD19+ IgD- CD27+ class-switched and CD19+ IgD+ CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of CD19+ CD27hi CD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts.
CONCLUSION: This study is the first to demonstrate a dysregulated proportion of CD19+ IgD+ CD27+ non-class-switched memory B cells and CD19+ CD27hi CD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.
METHODS: This cross-sectional case-control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry.
RESULTS: The frequency of CD19+ IgD+ CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both CD19+ IgD- CD27+ class-switched and CD19+ IgD+ CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of CD19+ CD27hi CD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts.
CONCLUSION: This study is the first to demonstrate a dysregulated proportion of CD19+ IgD+ CD27+ non-class-switched memory B cells and CD19+ CD27hi CD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.
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