Biomedical subjects

Eduard K Petershofen

Publications and source records attributed to Eduard K Petershofen.

4 recordsLinked to original sources

PubMed2006

In-frame triplet deletions in RHD alter the D antigen phenotype.

BACKGROUND: The deletion of three adjacent nucleotides in an exon may cause the lack of a single amino acid, while the protein sequence remains otherwise unchanged. Only one such in-frame deletion is known in the two RH genes, represented by the RHCE allele ceBP expressing a "very weak e antigen." STUDY DESIGN AND METHODS: Blood donor samples were recognized because of discrepant results of D phenotyping. Six samples came from Switzerland and one from Northern Germany. The molecular structures were determined by genomic DNA nucleotide sequencing of RHD. RESULTS: Two different variant D antigens were explained by RHD alleles harboring one in-frame triplet deletion each. Both single-amino-acid deletions led to partial D phenotypes with weak D antigen expression. Because of their D category V-like phenotypes, the RHD(Arg229del) allele was dubbed DVL-1 and the RHD(Lys235del) allele DVL-2. These in-frame triplet deletions are located in GAGAA or GAAGA repeats of the RHD exon 5. CONCLUSION: Partial D may be caused by a single-amino-acid deletion in RhD. The altered RhD protein segments in DVL types are adjacent to the extracellular loop 4, which constitutes one of the most immunogenic parts of the D antigen. These RhD protein segments are also altered in all DV, which may explain the similarity in phenotype. At the nucleotide level, the triplet deletions may have resulted from replication slippage. A total of nine amino acid positions in an Rhesus protein may be affected by this mechanism.

Alleles↗

PubMed2005

Presence of RHD in serologically D-, C/E+ individuals: a European multicenter study.

BACKGROUND: RHD blood group alleles with reduced or absent antigen expression are a clinically significant and heterogeneous group. STUDY DESIGN AND METHODS: To detail population genetics data on apparently D- individuals in central Europe, a six-center study was performed with participants from Austria, Germany, Slovenia, Switzerland, and Russia. A total of 1700 serologically D- samples, positive for C and/or E, were investigated. RESULTS: Observed unexpressed RHD alleles were 59 RHD-CE-D+ hybrid alleles, 9 apparently regular RHD, 1 new RHD(Y401X); DELs were 8 RHD(M295I), 6 RHD(IVS3+1G>A), and 1 new RHD(X418L); and weakly expressed RHDs were 2 weak D type 5, 1 weak D type 1, 1 RHD category VI type 1, and 1 novel weak D type 26. Although weak D type 26 was shown to have one of the lowest D antigen densities ever observed, it gave rise to anti-D immunization in a transfused D- individual. CONCLUSION: The relative occurrence of RHD among serologically D- samples, positive for C and/or E, differed significantly in the investigated central European regions. Considering the growing use of molecular typing techniques, correct identification of blood group alleles with scarce or missing antigen expression is of utmost clinical importance and requires reliable population-based frequency data.

Alleles↗

PubMed2005

Weak D type 1.1 exemplifies another complexity in weak D genotyping.

BACKGROUND: Weak D expression is caused by a large number of RHD alleles. Increasingly recommendations for D+ or D- transfusions are based on polymerase chain reaction (PCR) identification of certain RHD alleles. Possible sources of error are rare D variants that are inadvertently carrying known polymorphisms of frequent weak D types. STUDY DESIGN AND METHODS: Weak D donors were checked by direct column agglutination. In donors with unusually weak expression of D, the molecular weak D type was determined by weak D PCR and nucleotide sequencing. The serologic profile of a weak D type 1 variant was determined by agglutination serology and flow cytometry. RESULTS: Several donors in whom direct agglutination barely revealed any D expression were shown to carry the new RHD(L18V,V270G) allele dubbed weak D type 1.1. Initially, such donors had been mistyped as weak D type 1 by PCR. In a systematic study, weak D type 1.1 was shown to be present in 7 of 23 donors with very weak D expression who all lived in a restricted area of Northern Germany. Although weak D type 1.1 was typed D- or barely D+ by direct agglutination, it was easily detected by antiglobulin technique and was shown to carry about 600 antigens D per red blood cell. CONCLUSION: The observation of weak D type 1.1 with its distinct phenotype pinpointed to two general problems of current RHD genotyping strategies: Mistyping of alleles with additional mutations and striking geographic variation of the allele distributions.

ABO Blood-Group System↗

PubMed2002

Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571).

The Abl kinase inhibitor imatinib mesylate (STI571) has significant and rapid antileukemic activity in Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia (Ph(+) ALL) but such activity is usually of short duration except for a small proportion of patients. To determine the prognostic significance of early Bcr-Abl levels and changes in peripheral blood (PB) and bone marrow (BM), serial samples of 56 patients with relapsed or refractory Ph(+) ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction (PCR). Imatinib induced a complete hematologic response (CHR) or complete marrow response (marrow-CR) in 40 patients (good responders) and a partial (n = 2) or no (n = 14) remission in the remaining patients (poor responders). Compared with baseline, the median Bcr-Abl/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios decreased significantly in PB by 2.65, 2.64, and 3.11 log steps after 2 weeks, 4 weeks, and at the time of best response, respectively. In BM, the decline of median Bcr-Abl/GAPDH was 0.75, 1.37, and 2.78 logs, respectively. Thus, Bcr-Abl levels decreased more rapidly in PB than in BM (median time to best level 31 vs 39 days). Low Bcr-Abl/GAPDH ratios below 10(-4) in PB and below 10(-2) in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, Bcr-Abl levels (< 10(-2)) in BM of good responders after 4 weeks discriminated between 2 groups of patients with significantly different median time to progression (139 vs 22 days). The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies.

Antineoplastic Agents↗