Decay‐accelerating factor (CD55) deficiency phenotypes in Japanese

Abstract

Decay‐accelerating factor (DAF, CD55) is a complement regulatory glycoprotein that expresses the Cromer‐system blood group antigens. Two, very rare, inherited DAF‐deficiency phenotypes, Inab and Dr(a–), were identified in Japanese propositi. Red cells of the Inab phenotype propositus had no Cromer‐system antigens and did not bind monoclonal anti‐DAF. The Inab propositus was homozygous for a DAF non‐sense mutation, converting the Trp53 codon to a stop codon; her parents were heterozygous for this mutation. This is the same mutation as that previously found in the original Inab phenotype propositus. Haemagglutination‐inhibition titrations of the serum of the Inab propositus with soluble‐recombinant DAF demonstrated that anti‐IFC represents a mixture of antibodies to all four DAF short consensus repeat domains. The Dr(a–) individual had very low levels of Cromer‐system antigens and DAF on her red cells. Loss of a TaqI restriction site from DAF exon 5 suggested that she has a previously detected mutation, encoding a Ser165Leu substitution. Red cells of the two propositi did not show abnormal levels of lysis in an acid lysis test, but after blocking of CD59 with monoclonal antibody, Inab phenotype red cells showed more lysis than Dr(a–) red cells, and Dr(a–) cells showed substantially more lysis than control cells.

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

“…Interestingly, however, it has been reported that DAF (CD55) deletion, also known as the Inab phenotype, hardly alters the sensitivity of cells to lysis by complement and only with inhibition of CD59 does hemolysis occur in vitro [31–34]. Deficient expression of the complement regulatory proteins CD55 and CD59 has been found in a variety of human diseases (Table 1) [35–61], however, most prevalently in autoimmune hemocytopenia, autoimmune vasculitis, and other diseases involving dysregulated immune responses [41, 44, 62–68].…”

Molecular basis of Cromer blood group antigens

“…Furthermore, the remaining antigen, IFC (antibodies to which are produced by individuals of the Inab phenotype), is composed of sites in multiple SCR domains of DAF, as demonstrated by the inhibition of hemagglutination with soluble recombinant domain-deletion mutants of DAF. 18,23 This molecular composition is expected for the antibody response of individu- als who lack expression of DAF. Two separate mutations have been described in the Inab phenotype, and these are also listed in Table 1.…”

“…These results describe the molecular basis of 9 of the 10 assigned antigens of the Cromer blood group system. Furthermore, the remaining antigen, IFC (antibodies to which are produced by individuals of the Inab phenotype), is composed of sites in multiple SCR domains of DAF, as demonstrated by the inhibition of hemagglutination with soluble recombinant domain‐deletion mutants of DAF 18,23 . This molecular composition is expected for the antibody response of individuals who lack expression of DAF.…”

“…IFC is composed of multiple epitopes along the DAF glycoprotein. 18 The original Inab proposita 17 and a second, unrelated Inab individual, 18 both Japanese, have a nonsense mutation resulting in the amino acid substitution W53Stop in SCR1, whereas a third Japanese Inab proband had a point mutation in exon 2 of DAF (encoding SCR1) that produced a cryptic splice site, a 26-bp deletion, and a resultant frameshift leading to a stop codon immediately downstream. 20 Thus, in all Inab individuals analyzed to date, there is a stop codon that terminates DAF near the end of SCR1, so no full-length DAF glycoprotein is produced.…”

“…17,18,20 This is consistent with the finding that anti-IFC that is produced by Inab individuals recognizes multiple epitopes on the DAF glycoprotein. 18 In this report, we extend and essentially complete this molecular analysis of the Cromer system antigens, by elucidating the amino acid changes that underlie the five remaining antigens: Tc c , Es a , WES a , WES b , and UMC.…”