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

In paroxysmal nocturnal hemoglobinuria (PNH), hematopoietic cells lacking glycosylphosphatidylinositol (GPI)-linked proteins on their surface (GPIneg) exist alongside normal (GPI+) cells. Analysis of natural killer (NK) cell subsets in 47 PNH patients revealed that the ratio of CD56bright:CD56dim NK cells differed in the GPI+ and GPIneg populations, with GPInegCD56bright NK cells significantly more abundant in peripheral blood than their normal GPI+ counterparts. Indeed, GPI+CD56bright 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 GPI+ 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 GPI+ and GPIneg populations in this disease. •Paroxysmal nocturnal hemoglobinuria identifies a role for GPI-linked proteins in the homeostasis of human NK cell subsets.•GPI-deficient NK cells exhibit impaired chemotactic responses.