Molekulare Blutgruppenbestimmung

Zusammenfassung

Die erste molekulare Analyse einer menschlichen Blutgruppe erfolgte 1983 mittels eines Restriktions-Fragment-Längen-Polymorphismus (RFLP) am System Xg. Seither wurden in unzähligen Studien die molekularen Ursachen für Blutgruppen und deren Antigene erforscht,und das resultierende Wissen für eine ständige Verbesserung der entsprechenden Analysemethoden verwendet. Die Untersuchung kausaler Punktmutationen (Single Nucleotide Polymorphism, SNP) aller 36 von der International Society for Blood Transfusion (ISBT) anerkannten Blutgruppensysteme erlaubt heute eine der Serologie ebenbürtige, exakte Vorhersage der Blutgruppenantigene. In Patienten wird die molekulare Blutgruppenbestimmung bevorzugt in Form von Einzelprobenanalytik für die Diagnose von RhD-Varianten eingesetzt, um damit transfusionsrelevante Entscheidungen bezüglich RhD zu treffen und um die Rh-Prophylaxe noch zielsicherer zu steuern. An Spenderproben und im Hochdurchsatz ermöglicht die Blutgruppen-Genotypisierung die Schaffung einer ausreichenden Anzahl von Spender-Datensätzen, um immunisierte Patienten bestverträglich zu transfundieren oder deren Immunisierung bereits im Ansatz zu vermeiden. Gleichzeitig werden heutzutage an den gleichen Proben zusätzlich eine Vielzahl weiterer SNPs zur Identifikation von Spendern mit seltener Negativität für hochfrequente Antigene getestet. Derartig umfassende Spender-Datensätze werden bereits ideal genutzt für „In-silico-Kreuzproben“ eingesetzt. Next Generation Sequencing (NGS) ist auch in der Transfusionsmedizin der „neue Stern am Horizont“ und wird vermutlich innert weniger Jahre eine wichtige Rolle in der Analyse kompletter Blutgruppengenome (chronischer) Empfänger spielen. Blutgruppenbestimmung als frühestes Beispiel echter personalisierter Medizin wird in ihrer molekularen Version mit dazu beitragen, den gebührenden Platz der Transfusionsmedizin in der modernen Medizin zu behaupten.

Abstract

The first molecular analysis of a human blood group was performed using a Restriction Fragment Length Polymorphism (RFLP) on Xg in 1983. Since then, a panoply of studies addressing the genetic background of human blood groups has enormously broadened knowledge, with steady improvement of blood group genotyping procedures. Targeting Single Nucleotide Polymorphisms (SNPs) of all 36 human blood group systems, as currently recognized by the International Society for Blood Transfusion ISBT, allows for exact blood group antigen predictions, with accuracies comparable to those of serology. Blood group genotyping in patients is mainly done for the discrimination of RhD-variants due to their relevance for blood transfusion and in order to improve guided Rh prophylaxis. Among donors, high-throughput genotyping is used to assure supply of well-matched blood to recipients with existent allo-antibodies, or to avoid allo-immunizations up front. Capability of modern techniques for the simultaneous analysis of dozens of SNPs, allows for parallel identification of donors with rare negativity for high-frequency-antigens. Comprehensive donor-data sets have already been used in an ideal way for “in silico-matching” approaches. Next Generation Sequencing is a new star on the horizon and is envisioned for improved (chronic) recipient blood group analysis. Using molecular techniques, transfusion medicine the earliest example of truly personalized medicine, will keep its place in modern medicine.

Schlüsselwörter

Blutgruppe - Gen - Genotyp - molekulare Blutgruppenbestimmung - Blutgruppen-Genotypisierung

Key words

blood group - gene - genotype - molecular blood group typing - blood group genotyping

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