Intrinsic defects in erythroid cells from familial hemophagocytic lymphohistiocytosis type 5 patients identify a role for STXBP2/Munc18-2 in erythropoiesis and phospholipid scrambling

Experimental Hematology
E B KostovaR van Bruggen

Abstract

Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is a rare genetic disorder caused by mutations in STXBP2/Munc18-2. Munc18-2 plays a role in the degranulation machinery of natural killer cells and cytotoxic T lymphocytes. Mutations in STXBP2/Munc18-2 lead to impaired killing of target cells by natural killer cells and cytotoxic T lymphocytes, which in turn results in elevated levels of the inflammatory cytokine interferon γ, macrophage activation, and hemophagocytosis. Even though patients with FHL-5 present with anemia and hemolysis, no link between the disease and the erythroid lineage has been established. Here we report that red blood cells express Munc18-2 and that erythroid cells from patients with FHL-5 exhibit intrinsic defects caused by STXBP2/Munc18-2 mutations. Red blood cells from patients with FHL-5 expose less phosphatidylserine on their surface upon Ca(2+) ionophore ionomycin treatment. Furthermore, cultured erythroblasts from patients with FHL-5 display defective erythropoiesis characterized by decreased CD235a expression and aberrant cell morphology.

References

May 29, 2004·Biochimica Et Biophysica Acta·Robert F A ZwaalEdouard M Bevers
Aug 11, 2011·Blood·Michael B JordanKenneth L McClain
Jan 18, 2012·Annual Review of Medicine·G E Janka
Jun 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Patricia Perez-CornejoVictor Faundez

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Citations

Sep 23, 2020·Journal of Cellular Physiology·Bor L Tang

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