invited lecture: "partial D", ISBT

by Christoph Gassner

At the 2005 International Society for Blood Transfusion (ISBT) Conference in Athens an invited lecture was given: “Partial D and its clinical significance”. For a pdf-file of the presented lecture, please contact: christoph.gassner@c-gassner.com. The respective abstract has been published in Vox Sang 2005, Volume 89, Supplement I July 2005:

Partial D and its clinical significance.

Christoph Gassner

Central Institute for Blood Transfusion and Immunological Dept., Innsbruck, Austria

Partial D feature D antigen alteration, often identified as distinct “partial” D epitope loss. The clinical impact of partial Ds is due to the ability of their carriers to form anti-D antibodies upon confrontation with regular D after transfusion, or pregnancy. This leads to the – naively spoken – contradictory finding of an allo anti-D antibody in a D positive individual in connection with a negative autocontrol. The antibodies themselves include the same fatal clinical potential as anti-D antibodies of D negative individuals, but may be even more hazardous since unexpected in D positive individuals a priori. D categories (II to VII) represent a nomenclatorily defined subgroup of partial Ds.

The molecular cause of partial D lies within single (caused by point mutation in the respective RHD gene sequence), or multiple amino acid exchanges (caused by gene conversion events leading to RHD-RHCE-RHD hybrid genes) which determines a qualitative D antigen alteration, rendering them distinguishable from regular D by a partial D carriers immune system.

Nowadays, transfusion specialists and gynaecologists are more or less aware of these facts and are taking them into consideration in the clinical setting. Most partial D exhibit decreased D antigen density, enabling principal recognition of them. However, routine serological methods may not properly recognise all partial Ds and will identify their carriers after immunisation only, which represents a reactive diagnostic/therapeutic attitude second best to an actively prognostic one. This actively prognostic proceeding with respect to early detection of partial Ds became widely feasible by RHD DNA typing techniques.

Currently, routine RHD DNA typing techniques offer an affordable, accurate and fast approach to an unambiguous identification of partial Ds and their reliable discrimination from weak D types, not at risk for allo anti-D immunisation. A reasonable proactive proceeding could e.g. demand for (once in a lifetime) routine RHD DNA typing of all weakly expressed Ds as defined by serology, since most partial Ds also meet this phenotype. RHD allele frequencies and their geographical and regional prevalence will certainly have an important impact on DNA typing strategies and their (mandatory) specificities.

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