Introduction
The nomenclature based on "weak D types" was first used in the publication Blood 1999 Jan 1;93:385-93 for a host of different RHD alleles that expressed a weak D phenotype.
Once additional examples for similar RHD alleles were found, the same nomenclature was applied and consecutive numbers were given to such alleles. For a current updated list of weak D types please refer to the RhesusBase .
However, the procedure of distributing these numbers and the minimally required criteria for using the "weak D nomenclature" were not publically defined. The issue is of some practical interest and was publically discussed during the Rhesus flow cytometry session at the 4th International Workshop on Monoclonal Antibodies against Human Red Blood Cells and Related Antigens at the INTS in Paris on 19 July 2001 with participation by Drs Marion Scott & Geoff Daniels , BITS Bristol.
This webpage was designed to present a possible solution and to avoid any confusion that is likely to occur if researchers start assigning weak D type numbers essentially at random. The webpage may be a guide for a "standard" procedure and applying the criteria detailed herein would guarantee that publication of any "weak D type" would suffice to a common standard of quality for characterization of new RHD alleles with alleged weak D phenotype.
Suggested requirements
Principles: Full length coding sequence (CDS) established by sequening, non-exofacial location, weak expression of antigen D and documentation in the public record.
1. A new RHD allele as defined by the nucleotide sequencing of the full length RHD coding sequence, either as cDNA or from genomic DNA covering all 10 RHD exons.
2. At least one amino acid substitution located in the membrane or below the membrane of the red blood cell. Usually, no amino acid substitution will be present at or above the membrane as this is likely to cause a partial D phenotype.
3. Proof of a weak D phenotype by a peer approved method. The prefered method is antigen D density determination of less than about 5,000 antigen D per red blood cell using by a flow cytometry method. As an alternative, weak reactivity by standard serology with monoclonal antibodies of IgM or IgG type in tube or gel is also acceptable.
4. Deposition of the RHD allele in one of the nucleotide sequence databases. This deposition should be hidden until after the assignment of the weak D type number. The initial deposition should be made without using any weak D type number, which of course would not be available at the time of deposition. See an example for the weak D type 1 allele .
Procedure for deposition
Principle: Assigned weak D types should be made public shortly after assigment.
1. Once the suggested requirements 1 to 4 are met, a weak D type number can be requested. Evidence for the suggested requirements, like a nucleotide database entry, should be provided by email or fax.
2. Upon assigning a weak D type number the nucleotide sequence entry should be amended accordingly and the entry should be made public by the authors shortly.
3. Any assigned weak D type will be entered into the RhesusBase and made public no later than 3 months after assignment.
Conclusion
Following the suggested procedure would avoid the likely possibility that weak D type numbers are assigned and the pertinent alleles (inadvertantly, lack of interest) would never be published. In addition, the "source" of the allele can be documented.
Of course, researchers may still dub their allele with the usual partial D nomenclature or use any other means of applying a nomenclature that they deem suitable.
Summary of all published weak D types
Example for a nucleotide database entry
OMIM entry for weak D type 1
The RHD Mutation Database
Rhesus Immunization Registry
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