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Results for “Histocompatibility Testing”

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PubMed1977

Autoantibody against B lymphocytes.

The sera of 20 out of 99 (20%) normal males and females were shown to have antibodies that kill their own B lymphocytes. The sera were specifically cytotoxic to B lymphocytes and not T lymphocytes. Allogeneic B lymphocytes were also killed by these autocytotoxins. Maximum killing of B lymphocytes occurred when the incubation temperature in serum was 5 degrees C and complement incubation temperature was 20 degrees C. Under these cold conditions, some sera reacted up to a dilution of 1/16. These results suggest that positive B-lymphocyte crossmatches found in kidney transplantation do not detect alloantibodies. Since the B-cell autoantibodies tend to appear at the time of immunisation, their role as autoregulators of the antibody response is an intriguing possibility.

Autoantibodies↗
PubMed1999

Associations of MHC genes with levels of caries-inducing organisms and caries severity in African-American women.

The aim of this investigation was to evaluate the relationship between MHC alleles at the HLA-DRB1, DQB1 and TNFa microsatellite loci and levels of oral bacteria that play a role in the etiology of dental caries, and the DMFS index in 186 AA primparous women. The average age of the cohort was 20.8+/-3.7 years. The median DMFS index was 9 (range 0-68). High levels of S. mutans were positively associated with DRB1*3 and DRB1*4 presence (p < or = 0.005). DRB1*8 was positively associated with higher levels of S. mutans as a percentage of total Streptococci (p = 0.04). DRB1*1 was positively associated with high levels L. casei (p = 0.04). DQB1 alleles were not observed associated with oral bacterial levels. TNFa allele 103 was negatively associated (p = 0.04), and TNFa 117 was positively associated (p = 0.007), with high levels of L. acidophilus. No significant associations were observed between any DRB1, DQB1 or TNFa allele and the DMFS index. These results support an hypothesis of an association between host HLA class II and TNFa genetic profile and colonization of S. mutans, L. casei, and L. acidophilus thought to be pathogens involved in the etiology of dental caries.

Adolescent↗
PubMed1983

The MHC in human bone marrow allotransplantation.

In this chapter, we have considered the theoretical and practical background of bone marrow transplantation. The immune response and its regulation by genes within the major histocompatibility complex, particularly of the I region of the mouse and of the HLA-D/DR region in man, is of central importance in both graft acceptance (rejection) and graft-versus-host disease. Methods which are available for typing alleles at the HLA-A, -C, -B, -DR and complotype (BF, C2, C4A, C4B) loci, have been considered in detail. The extent to which recombination affects specific alleles on haplotypes within families is discussed, as is the occurrence of linkage disequilibrium and extended haplotypes in populations of unrelated individuals. Because the HLA-DR and complotype region in man is thought to be critical for the success of bone marrow transplantation, methods for typing of HLA-D by both the HTC and PLT approaches have been examined. Although HLA-D/DR assignments are easily made in normal subjects, they are ambiguous in about 50 per cent of candidates for bone marrow transplantation, including, particularly, patients with aplastic anaemia, leukaemia, and severe combined immunodeficiency. In this setting, it is particularly important to obtain additional information by modification of HLA-D typing procedures and through complotype and GLO allele determinations in all family members. Finally, we can hope that there will be an increased possibility of using non-family donors through methods for removing cytotoxic T cells from donor marrow and through the identification, in the general population, of individuals who are genotypically similar or identical to the recipient. In this regard, the recognition that some 30 per cent of chromosome 6 in caucasians (50 per cent of individuals) bear extended haplotypes, which include a relatively fixed set of alleles particularly in the HLA-B, -DR, complotype and GLO regions, offers considerable promise.

Animals↗
PubMed2004

Ethics of PGD: thoughts on the consequences of typing HLA in embryos.

As with so many fields of study associated with assisted human reproduction, many ethical issues are raised by the practice of preimplantation diagnosis of inherited disease (PGD). Some are part and parcel of assisted conception, e.g.the rights of human embryos in vitro and of embryologists to establish them, carry out research and discard them. Others unique to clinical PGD were discussed at an earlier meeting on PGD (Edwards et al., 2003). Recent developments in PGD are discussed briefly in this Commentary, especially the ethics of designer babies.

Bioethics↗
PubMed2000

Genomic typing of minor histocompatibility antigen HA-1 by reference strand mediated conformation analysis (RSCA).

Disparities in minor histocompatibility antigen (mHAg) HA-1 are involved in the development of acute graft-versus-host disease (GvHD) in adult recipient after HLA-identical sibling donor hematopoietic stem cell transplantation. The mHAg HA-1 is an HLA-A*0201-restricted nonapeptide, which derives from the cleavage of a protein encoded at chromosome 19. The sequence analysis of HA-1 cDNA identified two alleles, termed HA-1H and HA-1R, which differ in only two nucleotides at 3' end of exon A, at positions 500 and 504. DNA-based methods for HA-1 typing were developed in 1998, using polymerase chain reaction with sequence-specific primers (PCR-SSP) and restriction fragment length polymorphism (PCR-RFLP). Here, we report the usefulness of reference strand mediated conformation analysis (RSCA), which was developed for mutation detection and typing of polymorphic loci, to discriminate between the two HA-1 alleles. We performed genomic typing of HA-1 locus in 203 HLA-A*0201-positive samples using RSCA and we confirmed these results by PCR-SSP. The results demonstrate the high reproducibility of this method and their strong correlation with the results obtained by PCR-SSP (99%). Only two samples showed disparity between the RSCA typing and the PCR-SSP. Direct sequencing of these samples confirmed that the correct allele assignment was that obtained by the RSCA typing. Furthermore, HA-1- RSCA-based typing provides additional information about the intronic structure of both alleles. With this approach, we describe the almost constant presence (99.2%) of a 5-bp deletion at intronic position 214-218 associated to the HA-1H allele, previously unidentified. We conclude that HA-1 genomic typing by RSCA is easy to perform and that could be used as a routine typing method.

Alleles↗
PubMed2001

Polymorphisms in the coding region of mtDNA and effects on clinical outcome of unrelated bone marrow transplantation.

The entire protein-coding region was divided into 45 fragments, separately amplified and analyzed for polymorphism by the PCR-SSCP (single-strand conformation polymorphism) method. The effect of polymorphism mismatching on the clinical outcome of unrelated bone marrow transplantation was studied to clarify whether products from mtDNA become minor antigens. Variability in PCR-SSCP pattern combinations of the 45 fragments suggests that each individual has a different polymorphism combination in the protein-coding region if all the coding regions were compared at the nucleotide sequence level. Nonsynonymous polymorphisms were found at relatively high frequency in MTATP8 and MTND3. Both the polymorphisms with and without substitution matched the peptide-binding motifs of HLA-A*0201. The effects of the polymorphism matching were retrospectively analyzed in 340 recipients transplanted with HLA-A, -B, -DRB1 allele-matched bone marrow from unrelated donors. There were no effects of polymorphism matching on the incidence of acute GVHD and cumulative disease-free survival. These results suggest that polymorphisms which generate peptides, with and without substitutions, that bind the same HLA molecule hardly influence GVHD because the difference between the HLA-peptide complexes is minute.

Bone Marrow Transplantation↗