Blood, Vol. 95 No. 8 (April 15), 2000:
pp. 2699-2708
Weak D alleles express distinct phenotypes
Franz F. Wagner,
Alexander Frohmajer,
Birgit Ladewig,
Nicole I. Eicher,
Cornelie B. Lonicer,
Thomas H. Müller,
Manfred H. Siegel, and
Willy A. Flegel
From Abteilung Transfusionsmedizin, Universitätsklinikum Ulm
and DRK-Blutspendedienst Baden-Württemberg, Institut Ulm, Ulm;
Biotest AG, Dreieich, Germany; ZLB Zentrallaboratorium,
Blutspendedienst SRK, Bern, Switzerland; Blutspendedienst des BRK,
München; DRK-Blutspendedienst Niedersachsen-Oldenburg, Institut
Oldenburg, Oldenburg, Germany; and DRK-Blutspendedienst
Sachsen, Institut Dresden, Dresden, Germany.
The weak D phenotype is caused by many different RHD alleles
encoding aberrant RhD proteins, raising the possibility of distinct serologic phenotypes and of anti-D immunizations in weak D. We reported
6 new RHD alleles, D category III type IV, DIM, and the weak D
types 4.1, 4.2.1, 4.2.2, and 17. The immunohematologic features of 18 weak D types were examined by agglutination and flow cytometry with
more than 50 monoclonal anti-D. The agglutination patterns of the
partial D phenotypes DIM, DIII type IV, and DIV
type III correlated well with the D epitope models, those of the weak D
types showed no correlation. In flow cytometry, the weak D types
displayed type-specific antigen densities between 70 and 4000 RhD
antigens per cell and qualitatively distinct D antigens. A Rhesus D
similarity index was devised to characterize the extent of qualitative
changes in aberrant D antigens and discriminated normal D from all
tested partial D, including D category III. In some rare weak D types,
the extent of the alterations was comparable to that found in partial
Ds that were prone to anti-D immunization. Four of 6 case reports with
anti-D in weak D represented auto-anti-D. We concluded that, in
contrast to previous assumptions, most weak D types, including
prevalent ones, carry altered D antigens. These observations are
suggestive of a clinically relevant potential for anti-D immunizations
in some, but not in the prevalent weak D types, and were used to derive
an improved transfusion strategy in weak D patients.