[Clinical features and diagnosis of paroxysmal nocturnal hemoglobinuria: correlates with the deficiency of GPI-anchored membrane proteins].

Glycosyl phosphatidylinositol (GPI)-anchored membrane proteins are deficient in the blood cells affected by paroxysmal nocturnal hemoglobinuria (PNH). The relation of the deficiencies of CD59 and CD14 with the clinical features of PNH are reported. CD59 binds to complement components C8 and C9 derived from human sera and inhibits the C5b-9-mediated hemolysis in a species-selective manner. The CD59-binding sites were revealed to be localized in the alpha subunit of C8 and in the "b" domain of C9 (thrombin fragment). The deficiency of CD59 in PNH is causatively related to the hemolytic features in PNH. A monocyte differentiation antigen, CD14, is deficient in the affected PNH monocytes. CD14 is reported to be one of the receptors to lipopolysaccharide (LPS). LPS-binding to the monocytes were revealed to be mediated through CD14 on monocytes. Enhancement of LPS-binding to monocytes by the presence of serum was not seen to PNH-affected monocytes. PNH-affected monocytes showed impaired TNF-alpha production in response to LPS. The deficiency of CD14 indicates the abnormality in PNH-affected monocytes, however, its significance in the clinical features of PNH is to be clarified.