1994 - present

The allele polymorphism of the RHD gene

Our main research focus is the molecular characterization of RHD alleles in whites.

We described more than 20 novel RHD alleles. Some of them were shown to be clinically relevant.

We established the molecular cause of the weak D phenotype, which was a 50-year old enigma in RH blood group serology. We refuted the long-standing dogma of a normal antigen D in probands with weak D antigen expression. Our methods and data allowed the correlation of anti-D immunization with distinct molecularly defined RHD alleles.

We showed that the reconsideration of previous serologic and clinical data for partial D in view of their underlying molecular structures is worthwhile and may reveal unexpected immunohematologic features.

Our basic research results had several spin-offs for the clinical practice. We try to rapidly introduce them in the routine as exemplified by our current and completed development activities.

Sample reference: 1999 1998 1997 1996 1995

Current development activities

 
1998 - present

Rhesus Immunization Surveillance - National Registry

In the German Guidelines for Blood Grouping and Blood Transfusion (Hemotherapy) ("Guidelines") a new method for RhD-typing in transfusion recipients has been recommended since December 1996. Many patients with weak D expression who were previously transfused with Rh-negative blood, has since been  transfused RhD-positive. The surveillance of all anti D-immunizations in carriers of the antigen D, of the RHD gene or of any segments thereof shall provide that no adverse effect of the new RhD-typing may remain undetected in the area of coverage of the "Guidelines". To retrieve data for comparison, probands shall be tested and registered, too, whose anti D-immunization is proven to have occurred before 1997.

We maintain the German national registry for anti-D immunizations in RhD positive patients.

We characterize the molecular structures of the RHD gene involved in these immunizations. The results will be evaluated to control inadvertant adverse effects of the recommended RhD-typing strategy.

Reference: WWW link
 

1996 - present

Development of strategies and methods for blood group genotyping

In collaboration with the Central Institute for Blood Transfusion, General Hospital, Innsbruck, Austria and the German Red Cross Blood Center, Oldenburg, Germany an easy-to-perform DNA-based method for the detection of the two RH genes and their alleles, including variant RHD alleles, was developed. The established exon-scanning RHD/CE polymerase chain reaction using sequence-specific primers complements current RH DNA typing strategies and was shown to be superior in the detection of variant RHD alleles.

Future work will focus on improving the versatility of the test system and its extension to other blood group genes and other blood group genotyping applications.

Sample references: 1998 1997
 

1995 - present

Monitoring of transfusion associated risk factors

The current literature is monitored on a continuous basis for known and new risk factors. We publish occasionally reviews for physicians and technician in clinical practice.

Current experimental work in collaboration with the Military Hospital Ulm is addressing potential contaminations in red blood cell components.

Current experimental work in collaboration with the German Red Cross Blood Center at Mannheim is focussing on the surveillance of non-hemolytic transfusion reactions and their association with anti-leukocytic and anti-thrombocytic antibodies.

Sample references: 1998 reviews 1996 1996 review

Completed R&D activities
 

1996 - 1997

The population frequency of sporadic nonfunctional alleles in human genes

The population frequency of sporadic nonfunctional alleles was not known for any gene under low selection pressure. We utilized the H blood group system, which is lacking prevalent nonfunctional alleles, for the derivation of that population frequency. The frequency of nonfunctional alleles at the H gene locus was calculated as 1 in 347 in a large white population (95% CI: 1:185-1:824). We showed that the Bombay blood group phenotype in whites is due to diverse, sporadic, nonfunctional alleles without any prevalent allele. Assuming similar rates of nonfunctional alleles in glycosyltransferase genes like ABO, current genotyping strategies may fail as often as once in about 300 individuals of blood group O. This conclusion has broad implications for any genotyping strategy because sporadic neutral alleles of such frequencies pose a serious obstacle for population-wide screening of many disease-associated genes.

Sample references: 1997    Habilitationsschrift
 

1995 - 1996

Application of solid-phase tests with pooled red cells to antibody screening in blood donors

Solid-phase test are very sensitive for detection of erythrocyte alloantibodies and suitable for large scale screening. We evaluated the utility of three solid-phase test for blood donor screening. All three solid-phase tests detected the alloantibodies, which were of higher titers and considered clinically relevant in blood components. A significant difference in antibody titers between the tests was not matched by a similar variance in the detection of donors with antibodies.

Sample reference: 1996
 

1994 - 1995

Routine procedure for RhD-typing

We developed and recommended a serologic procedure for routine RhD-typing, which later became mandatory in Germany.

Sample references: 1995
 

1994 - 1995

Evaluation of cytokine contamination in platelet blood components

Cytokines, like IL-1, IL-6, and TNF, are known to cause febrile nonhemolytic transfusion reactions. We tested platelet concentrates produced from buffy coats by a standard large-scale production process. These platelet blood components were shown to be virtually free of cytokines during 5 days of storage. We concluded that filtration is not required to reduce the recipient's cytokine exposure via such platelet concentrates.

Sample reference: 1995
 

1994

Risk estimates for transfusion-associated graft-versus-host disease due to homozygous HLA haplotypes

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur in transfusions of blood from HLA-homozygous persons to HLA-heterozygous persons who share a haplotype. We developed mathematical models to the associated risks using a combination of serology- and DNA sequence-based HLA haplotype frequencies. Our estimates were lower than those of previously published models, were in better agreement with the clinical experience, and explained in part the
observed discrepancy between TA-GVHD incidence in the United States and that in Japan.

Sample reference: 1995
 

last updated 26 Aug 1998