Christoph Gassner1, Irene Utz, Harald Schennach, Angela Ramoni, Hannes Steiner, Sabine Scholz, Ursula Kreklau, Günther F Körmöczi. 1. Blood Transfusion Service Zurich, Swiss Red Cross, Zurich, Switzerland; Central Institute for Blood Transfusion and Immunological Department, General Hospital and University Clinics Innsbruck, Innsbruck, Austria; Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria; Urology, Medical University Innsbruck, Innsbruck, Austria; inno-Train Diagnostik GmbH, Kronberg i.T., Germany; Labor Wisplinghoff, Cologne, Germany; Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
Abstract
BACKGROUND: Molecular variant RHD allele analysis is best complemented by detailed characterization of the associated D phenotype. STUDY DESIGN AND METHODS: Variant D types were characterized using molecular typing, RHD sequencing, extended serologic D antigen investigations, and flow cytometric D antigen quantification. RESULTS: We discovered three novel weak D types termed weak D Types 45.1, 75, and 76 with RHD nucleotide substitutions coding for amino acid exchanges in predicted intracellular RhD polypeptide stretches; antigen densities of approximately 1.990, 900, and 240 D sites per red blood cell were found, respectively. Adsorption-elution technique-supported D epitope mapping of these three weak D types demonstrated the expression of all tested D epitopes. Initial molecular typing of the three investigated samples by RHD gene exon scanning polymerase chain reaction using sequence-specific priming yielded a negative reaction for A1193 located in RHD Exon 9 and could be explained by specific mutations for weak D Types 45.1 (C818T, G1195A), 75 (G1194C), and 76 (A1215C). CONCLUSION: All novel weak D types expressed all tested D epitopes. It is of interest that for weak D Types 45.1, 75, and 76, similar alleles with a maximal divergence of one amino acid only, that is, weak D Types 45, 41, and 68, respectively, have been reported so far.
BACKGROUND: Molecular variant RHD allele analysis is best complemented by detailed characterization of the associated D phenotype. STUDY DESIGN AND METHODS: Variant D types were characterized using molecular typing, RHD sequencing, extended serologic D antigen investigations, and flow cytometric D antigen quantification. RESULTS: We discovered three novel weak D types termed weak D Types 45.1, 75, and 76 with RHD nucleotide substitutions coding for amino acid exchanges in predicted intracellular RhD polypeptide stretches; antigen densities of approximately 1.990, 900, and 240 D sites per red blood cell were found, respectively. Adsorption-elution technique-supported D epitope mapping of these three weak D types demonstrated the expression of all tested D epitopes. Initial molecular typing of the three investigated samples by RHD gene exon scanning polymerase chain reaction using sequence-specific priming yielded a negative reaction for A1193 located in RHD Exon 9 and could be explained by specific mutations for weak D Types 45.1 (C818T, G1195A), 75 (G1194C), and 76 (A1215C). CONCLUSION: All novel weak D types expressed all tested D epitopes. It is of interest that for weak D Types 45.1, 75, and 76, similar alleles with a maximal divergence of one amino acid only, that is, weak D Types 45, 41, and 68, respectively, have been reported so far.
Authors: Eva Maria Matzhold; Helene Polin; Günther F Körmöczi; Susanne Macher; Marlies Schönbacher; Thomas Wagner Journal: Transfusion Date: 2019-07-23 Impact factor: 3.157
Authors: Eva Maria Matzhold; Thomas Wagner; Camilla Drexler; Marlies Schönbacher; Günther F Körmöczi Journal: Transfus Med Hemother Date: 2019-04-29 Impact factor: 3.747