DEL in China: the D antigen among serologic RhD-negative individuals

Abstract

Background Providing RhD-negative red cell transfusions is a challenge in East Asia, represented by China, Korea, and Japan, where the frequency of RhD-negative is the lowest in the world. Findings Among 56 ethnic groups in China, the RhD-negative frequency in Han, the prevalent ethnicity, is 0.5% or less, similar to most other ethnic groups. The Uyghur ethnic group has the highest reported RhD-negative frequency of up to 4.7%, as compared to 13.9% in the US. However, an estimated 7.15 million RhD-negative people live in China. The RhD-negative phenotype typically results from a loss of the entire RHD gene, causing the lack of the RhD protein and D antigen. The DEL phenotype carries a low amount of the D antigen and types as RhD-negative in routine serology. The DEL prevalence in RhD-negative individuals averages 23.3% in the Han, 17% in the Hui and 2.4% in the Uyghur ethnicities. The Asian type DEL, also known as RHD*DEL1 and RHD:c.1227G > A allele, is by far the most prevalent among the 13 DEL alleles observed in China. Conclusion The purpose of this review is to summarize the data on DEL and to provide a basis for practical strategy decisions in managing patients and donors with DEL alleles in East Asia using molecular assays.

RhD alloimmunization by DEL variant missed in donor testing

“…With the advent of molecular diagnostics, another challenge emerged with the increasing existence of D variants ‐numbers of reports of immunized patients by weak or undetectable D 10,23,24 . Multiple case reports on RhD alloimmunization from Austria, Japan, Korea, China, and Taiwan proved the potential risk of D negative RBC in causing primary or secondary RhD alloimmunization 9,23,24 . Wagner FF et al described an anti‐D immunization in two recipients caused by a chimeric donor missed in routine serology and found by RHD PCR 25 .…”

“…More than 40 DEL alleles have been described so far. 8,9 Generally, the frequency of DEL among Europeans is 1:350 to 1:2000 which is much lower than in Asian countries. 10,11 It has been well known that Rh antigens are highly immunogenic, with D antigen being most potent, followed by c, E, C,e.…”

“…Routine serologic testing cannot detect these variants and are therefore mistyped as D negative. More than 40 DEL alleles have been described so far 8,9 . Generally, the frequency of DEL among Europeans is 1:350 to 1:2000 which is much lower than in Asian countries 10,11 .…”

When should RhD‐negative recipients be spared the transfusion of DEL red cells to avoid anti‐D alloimmunization?

“…The incidence of DEL varies from 0.2% among phenotypically RhD‐negative Europeans to 5.9%–33% among those of East Asian ethnicity (mostly Asian‐ type DEL, also known as RHD*DEL1 or RHD:c1227G > A allele) 5,6,7,8 . These vast differences in prevalence among world populations ought to be reflected in DEL management.…”

“…East Asia. 4,8 Among 17 East Asian recipients who developed anti-D or rebounded after transfusing exclusively phenotypic D-negative red cells, two (12%) experienced a delayed hemolytic transfusion reaction, while the remaining 15 (88%) showed no clinical signs of hemolysis. 6 Further, five (29%) patients seemed to be sensitized as a primary response and 12 (71%) as secondary response.…”