Preferential expression of human FcγRIII(PMN) (CD16) in paroxysmal nocturnal hemoglobinuria. Discordant expression of glycosyl phosphatidylinositol-linked proteins

Academic Article


  • The isoform of FcγRIII (CD16) expressed on PMN has a GPI membrane anchor, and in paroxysmal nocturnal hemoglobinuria (PNH) there is a deficiency in FcγRIII expression on PMN. Contrary to expectation, however, CD16 expression is preserved (albeit at reduced levels) in all affected PNH PMN that completely lack the GPI-anchored proteins DAF (CD55) and CD59. FcγRIII negative PMN are not observed in any of the six PNH patients examined in this study. Analysis of the molecular weight of both glycosylated and deglycosylated FcγRIII from PMN with reduced FcγRIII expression indicates no variations in size relative to normal donor FcγRIII(PMN). Indeed, the FcγRIII expressed at intermediate levels is phosphotidylinositol-specific phospholipase C (PI-PLC)-sensitive. Thus, there is no evidence suggestive of expression of a transmembrane isoform and all data indicate that FcγRIII(PMN) on affected cells in PNH is a GPI-linked isoform. With FcγRIII(PMN) expression preserved at reduced levels on affected cells in PNH, PMN from PNH patients retain the capacity to internalize the FcγRIII(PMN)-specific probe E-ConA (at reduced levels) as well as IgG-opsonized erythrocytes. Reduced expression of GPI-anchored molecules on PNH PMN is not restricted to FcγRIII(PMN) since intermediate levels of CD59 were also observed in the PNH PMN that were decay-accelerating factor (DAF)-negative and FcγRIII(PMN) intermediate. In addition, discordant expression of GPI-linked molecules in individual cells is not restricted to PMN since DAF+/CD14- monocytes were observed in one PNH patient. These data suggest that, when analyzed on an individual cell level, the GPI anchor defect in PNH is not absolute and must involve either a hierarchy of access of different protein molecules to available GPI anchors, distinct anchor biochemistries for the different proteins, or differential regulation of protein-anchor assembly.
  • Published In

    Author List

  • Edberg JC; Salmon JE; Whitlow M; Kimberly RP
  • Start Page

  • 58
  • End Page

  • 67
  • Volume

  • 87