Abstract
Although it has been suggested that paroxysmal nocturnal hemoglobinuria (PNH), idiopathic aplastic anemia (AA), and myelodysplastic syndromes (MDS) share immune-mediated bone marrow injury, the molecular events in the injury is still unclear. Currently we have shown that leukemic K562 cells became less sensitive to natural killer (NK) cells in vitro when the leukemic cells acquired PIG-A mutations (
Nagakura S et al, Blood 2002; 100: 1031–1037
). The decreased sensitivity was explained by a deficiency of stress-inducible and GPI-linked membrane proteins ULBP (Hanaoka N et al, Blood 2004; 104: 774a
). In general, the exposure of ULBP on cell membrane leads to activation of both NK and T cells expressing NKG2D, a receptor for ULBP. It is then conceivable that the ULBP-NKG2D engagement causes blood cell injury. In support of this idea, we detected both ULBP-expressing (ULBP+) blood cells (granulocytes or marrow cells) in 9 of 17 (53%) patients with PNH and killing of granulocytes of 4 the 9 patients by autologous lymphocytes. Granulocytes of healthy donors were negative for ULBP and intact in the killing assay. ULBP+ granulocytes were further detected in 24 of 45 (53%) patients with AA, and 10 of 21 (48%) patients with MDS, whereas ULBP+ granulocytes were detected in neither patients with autoimmune hemolytic anemia nor those with drug-induced marrow injury. Our study suggests not only that there was pathogenic stress to induce ULBP on blood cell membrane but also that the ULBP-NKG2D engagement was implicated in the pathogenesis of marrow failure, at least in a part, of patients with PNH and its related disorders. We thus propose that membrane ULBP would be of potential probe for the diagnosis of immune-mediated marrow injury and the evaluation of its treatment.Author notes
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2005, The American Society of Hematology
2005
