Weak D alleles express distinct phenotypes

Author:

Wagner Franz F.1,Frohmajer Alexander1,Ladewig Birgit1,Eicher Nicole I.1,Lonicer Cornelie B.1,Müller Thomas H.1,Siegel Manfred H.1,Flegel Willy A.1

Affiliation:

1. 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.

Abstract

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 DIVtype 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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