Identification of human erythrocyte blood group antigens on decay- accelerating factor (DAF) and an erythrocyte phenotype negative for daf

Abstract

Decay accelerating factor (DAF) is a glycoprotein present on the surfaces of many types ofcells in contact with plasma, including erythrocytes, leukocytes, and platelets (reviewed in reference 1). A small amount ofDAF is also present in serum. Numerous investigators have demonstrated that DAF inhibits the action of C3 convertases on cell surfaces, and its absence has been shown to be at least partially responsible for the abnormal sensitivity to lysis by complement exhibited by erythrocytes of patients with the acquired stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) (2). Hereditary absence of DAF has not been previously described .Tca and Cra are high-frequency human erythrocyte antigens . These antigens are part of a family of blood group antigens, designated Cromer related, which are all absent from the null phenotype cell IFC -, or Inab (3). Recently, Spring and colleagues (4) have identified two monoclonal antibodies which bound to high frequency red cell antigens absent from the Inab phenotype. They also demonstrated that these antibodies, as well as several human antisera to Cromer-related antigens, bound to a 70-kD glycoprotein when used to stain immunoblots of human erythrocyte membrane proteins . Because the wide tissue distribution of mAb reactivity, along with some of the biochemical characterization and immunoblotting data, was similar to that of DAF, we investigated whether the Cromer-related antigens Cra and Tca resided on the DAF molecule . Volume 167 June 1988 1993-1998 Materials and Methods Brief Definitive Report DAF was purified from random donor human erythrocytes by the method of NicholsonWeller (5), as modified by Sugita et al . (6). Resultant material was homogeneous as analyzed by SDS-PAGE and silver staining, and C3 convertase inhibitory activity was intact, as measured by the ability of purified DAF to inhibit lysis of sheep erythrocytes sensitized with antibody and bearing human complement components 1 and 4b (EACI, 4b) (5).

A novel mechanism of complement-independent clearance of red cells deficient in glycosyl phosphatidylinositol–linked proteins

“…33 The cause of hemolysis in this patient is unclear because deficiency of DAF alone does not cause hemolysis. [37][38][39] This suggests that in this C9-deficient PNH patient, as in the mice described here, an increased complement-independent clearance occurs that shortens the half-life of PNH RBCs. The characterization and understanding of this pathway will enable us to delineate its possible clinical importance and possibly determine whether it might also play a role in other diseases with increased RBC clearance.…”

Dr(a-) polymorphism of decay accelerating factor. Biochemical, functional, and molecular characterization and production of allele-specific transfectants.

“…Several polymorphisms have been identified in the noncoding regions ofthe DAF gene by restriction fragment length polymorphisms (RFLP) analysis (3,27). Recently the Cromer blood group antigens (reviewed in 28) have been shown to reside on the DAF molecule (29), so that the serologically identified Cromer blood group alleles mark polymorphisms in the encoded DAF protein. These Cromer blood group phenotypes thus provide a basis for biochemical and functional investigation of alternate forms of DAF.…”

Increased Susceptibility of Decay-Accelerating Factor Deficient Mice to Anti-Glomerular Basement Membrane Glomerulonephritis

“…These individuals differ from PNH patients in that they lack DAF expression in all their tissues, whereas DAF deficiency in PNH patients, resulting from somatic mutations of a gene critical to GPI-anchor biosynthesis (21), is limited to affected blood cells and occurs in conjunction with CD59 dysfunction (12). Furthermore, although DAF gene mutation apparently did not lead to PNH-like disease, two of the five individuals had an intestinal inflammatory disorder (19,20). However, due to the rare nature of DAF gene mutation in the human population, it has not been possible to determine whether such individuals are more susceptible to complement-mediated inflammatory tissue damage.…”

“…Although in vitro studies have demonstrated that DAF expressed on these cells is functional as a C3 convertase inhibitor (17,18), thus far little direct evidence is available to corroborate the expectation that DAF plays a protective role in vivo on nonvascular cells from complement-mediated injury. In humans, rare cases of complete DAF deficiency due to germline mutation of the DAF gene (Inab serological phenotype) have been identified (19,20). These individuals differ from PNH patients in that they lack DAF expression in all their tissues, whereas DAF deficiency in PNH patients, resulting from somatic mutations of a gene critical to GPI-anchor biosynthesis (21), is limited to affected blood cells and occurs in conjunction with CD59 dysfunction (12).…”