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Decay-accelerating factor (CD55) deficiency phenotypes in Japanese
G L Daniels1, C A Green, G Mallinson
1Bristol Institute for Transfusion Sciences, UK. geoff.daniels@msmail.nbs.nhs.uk
Insights
Rare inherited deficiencies in Decay-accelerating factor (DAF, CD55) were identified in Japanese individuals, revealing novel mutations impacting complement regulation and blood group antigen expression.
Area of Science:
- Immunology
- Genetics
- Hematology
Background:
- Decay-accelerating factor (DAF, CD55) is a crucial complement regulatory protein.
- DAF expresses Cromer-system blood group antigens on erythrocytes.
- Inherited DAF deficiencies are exceptionally rare, with limited documented cases.
Observation:
- Two distinct DAF-deficiency phenotypes, Inab and Dr(a-), were identified in Japanese subjects.
- The Inab phenotype exhibited a complete absence of Cromer antigens and DAF binding.
- The Dr(a-) phenotype showed significantly reduced Cromer antigens and DAF levels.
Findings:
- The Inab propositus was homozygous for a previously identified DAF nonsense mutation (Trp53 stop codon).
- The Dr(a-) individual possessed a mutation causing a Ser165Leu substitution in DAF.
- Antibodies in Inab serum recognized all four DAF short consensus repeat domains.
Implications:
- These findings elucidate the genetic basis of rare DAF-deficiency phenotypes.
- Understanding these mutations enhances knowledge of complement regulation and blood group antigen complexities.
- Further research can explore the clinical significance and potential therapeutic targets related to DAF function.
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.