Page 226 - 2019_03-Haematologica-web

Ferrata Storti Foundation
Haematologica 2019 Volume 104(3):632-638
Blood Transfusion
Somatic mosaicisms of chromosome 1 at two different stages of ontogenetic development detected by Rh blood group discrepancies
Eva-Maria Dauber,1 Wolfgang R. Mayr,1 Hein Hustinx,2 Marlies Schönbacher,1 Holger Budde,3 Tobias J. Legler,3 Margit König,4 Oskar A. Haas,4
Gerhard Fritsch4 and Günther F. Körmöczi1
1
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Austria; 2Blood Transfusion Service, Swiss Red Cross (SRK), Bern, Switzerland; 3Department of Transfusion Medicine, University of Göttingen, Germany and 4Children’s Cancer Research Institute, St. Anna Hospital, Vienna, Austria
ABSTRACT
Spontaneous Rh blood group changes are a striking sign, reported to occur mainly in patients with hematologic disorders. Upon routine blood grouping, 2 unrelated individuals showed unexplained mixed red cell phenotype regarding the highly immunogenic c antigen (RH4), clinically relevant for blood transfusion and fetomaternal incompatibility. About half of their red cells were c-positive, whereas the other half were c-negative. These apparently hematologically healthy females had no history of transfusion or transplantation, and they tested negative for chimerism. Genotyping of flanking chromosome 1 microsatellites in blood, finger nails, hair, leukocyte subpopulations, and erythroid progen- itor cells showed partial loss of heterozygosity encompassing the RHD/RHCE loci, spanning a 1p region of 26.7 or 42.4 Mb, respectively. Remarkably, in one case this was detected in all investigated tissues, whereas in the other, exclusively myeloid cells showed loss of heterozy- gosity. Both carried the RhD-positive haplotypes CDe and the RhD-neg- ative haplotype cde. RHD/RHCE genotypes of single erythroid colonies and dual-color fluorescent in situ hybridization analyses indicated loss of the cde haplotype and duplication of the CDe haplotype in the altered cell line. Accordingly, red cell C antigen (RH2) levels of both propositae were higher than those of heterozygous controls. Taken together, the Rhc phenotype splitting appeared to be caused by deletion of a part of 1p fol- lowed by duplication of homologous stretches of the sister chromosome. In one case, this phenomenon was confined to myeloid stem cells, while in the other, a pluripotent stem cell line was affected, demonstrating somatic mosaicism at different stages of ontogenesis.
Introduction
Antigens of the Rh blood group system are very immunogenic and routinely typed in pretransfusion testing and prenatal investigations, as antibodies against these structures may elicit hemolytic transfusion reactions or hemolytic disease of the fetus and newborn. D (RH1) and c (RH4) are clinically the most important Rh antigens, as the frequently encountered anti-D and anti-c alloantibodies have pro- nounced hemolytic potential. All Rh antigens reside on RhD and RhCcEe polypep- tides encoded by the RHD and RHCE genes, respectively, mapped to the short arm of chromosome 1 (p34-36).1,2
Unambiguous Rh typing is mandatory to account for the clinical relevance of these antigens. However, Rh-mismatched transfusion or hematopoietic stem cell transplantation (iatrogenic chimerism) may lead to concurrent presence of Rh anti- gen-positive and -negative red blood cells (RBCs) in the circulation. Importantly, mixed-field agglutination in serological Rh typing was noted also in non-iatrogenic
Correspondence:
GÜNTHER F. KÖRMÖCZI
guenther.koermoeczi@meduniwien.ac.at
Received: July 5, 2018.
Accepted: September 20, 2018. Pre-published: September 20, 2018.
doi:10.3324/haematol.2018.201293
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/3/632
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
632
haematologica | 2019; 104(3)
ARTICLE