Altered natural killer cell subset homeostasis and defective chemotactic responses in paroxysmal nocturnal hemoglobinuria

Abstract

In paroxysmal nocturnal hemoglobinuria (PNH), hematopoietic cells lacking glycosylphosphatidylinositol (GPI)-linked proteins on their surface (GPIneg) exist alongside normal (GPI1) cells. Analysis of natural killer (NK) cell subsets in 47 PNH patients revealed that the ratio of CD56bright:CD56dim NK cells differed in the GPI1 and GPIneg populations, with GPInegCD56bright NK cells significantly more abundant in peripheral blood than their normal GPI1 counterparts. Indeed, GPI1CD56bright NK cells were not detected in the peripheral blood of some patients, suggesting their trafficking to a niche unavailable to the GPInegCD56bright NK cell population. Defective cellular trafficking in this disease was supported by findings showing differential chemokine receptor expression between GPI1 and GPIneg NK cells and impaired stromal cell–derived factor 1 (SDF-1)–induced chemotaxis of GPIneg NK cells. Our results indicate a role for GPI-linked proteins in NK cell subset homeostasis and suggest that differential chemokine responses might contribute to the balance of GPI1 and GPIneg populations in this disease.