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Biomedical subjects

A Hajek-Rosenmayr

Publications and source records attributed to A Hajek-Rosenmayr.

At least 19 recordsLinked to original sources

Activated human T lymphocytes express MHC class I heavy chains not associated with beta 2-microglobulin.

We present here the molecular characterization of a new activation-induced surface structure on human T lymphocytes, termed LA45, with high homology (93% at protein level) to MHC class I molecules. Antigen modulation and sequential immunoprecipitation experiments revealed that LA45 and HLA class I proteins do not crossreact with the corresponding antibodies. Furthermore, LA45 is not associated with beta 2-m. On the other hand, we could show that the separation of HLA-A,B,C and beta 2m molecules, induced by SDS-denaturation, leads to a conformational change in the heavy chain in such a way that it becomes reactive with LA45. The 90/45 kD LA45 proteins thus appear to be non-beta 2m-associated MHC class I alpha chains that are selectively expressed by activated but not by resting human T lymphocytes.

Amino Acid Sequence↗

Influence of HLA phenotypes on the inhibition of in vitro alloreactivity by cyclosporine.

Interindividual variations in the immunosuppressive effect of Cyclosporine have been observed in clinical organ transplantation. Searching for an in vitro correlate we investigated a possible relation between inhibition of alloresponsiveness by CsA and the HLA phenotypes of the responder or stimulator in mixed lymphocyte reactions. Peripheral blood mononuclear cells from 28 healthy volunteers were used as responder or stimulator cells (gamma-irradiated) and the inhibitory effect of graded amounts of CsA was determined in 130 criss-cross combinations. Sensitivity of alloresponsiveness to the drug was expressed as the dose causing 50% inhibition (ED50) and was read from the inhibition curves generated after four-parameter logistic curve fitting. ED50 ranged from 0.35 ng/ml to 33.4 ng/ml and correlated only weakly with the magnitude of the response (r = 0.12). In MLC with HLA DR4-positive responder cells, ED50 was significantly lower (Pc = 0.0035, Kruskal Wallis) when compared with MLC with responder cells of other DR haplotypes. For HLA DR5-positive responder cells ED50 was significantly higher (Pc = 0.042) when compared with DR5-negative responder cells. No significant correlation between ED50 and any particular haplotype of the stimulator cells could be observed. Sensitivity to CSA did not differ in MLC with 1 or 2 mismatches in the HLA-DR locus. In summary, we found that sensitivity of in vitro alloreactivity was different for particular HLA DR phenotypes, which may have important implications for the immunosuppressive therapy of transplanted patients with cyclosporine.

Cyclosporins↗

[The HLA system and habitual abortion].

HLA-antigens are extremely polymorphic. A calculation of the polymorphism shows a number of 398.476.343 possible HLA-phenotypes, if HLA-A, -B, -C and -DR antigens are taken into account. The compatibility of HLA-antigens of recipient and donor plays a crucial role in transplantation: HLA-antigens are the traits, which are recognized by the immune system of the recipient in the frame of a rejection of the transplant or by the donor in the frame of a graft-versus-host reaction. Large international statistics show that HLA-incompatibility between recipient and donor leads to short transplant function periods, while compatibility brings about good transplant function. Therefore, matching of HLA-antigens plays an important role in transplantation of solid organs, mainly kidneys (3, 4, 5), and is completely necessary in bone marrow transplantation. Also in pregnancy, HLA-antigens are important: If HLA compatibility between mother and child is high, the risk for habitual abortion is higher than in normal pregnancies (6, 7).

Abortion, Habitual↗

[Serologic diagnosis and therapeutic possibilities in habitual abortion].

Immunological laboratory investigations and success in the therapy of habitual abortion have led to a new view of the disease. Though we are currently unable to fully understand the underlying mechanisms, it seems to be generally accepted that insufficient production of HLA antibodies at an early stage of gestation is pathogenetically involved. Employing sensitive methods (IPI = immune phagocytosis inhibition assay) antibodies directed against fetal (paternal) histocompatibility antigens can be detected in the sera of healthy women already in the fifth week of gestation. The lack of such antibodies in the sera of aborting women is therefore an important diagnostic criterion. Strikingly good histocompatibility between the partners in couples with habitual abortion is occasionally encountered, providing an explanation for the lack of immune response in these cases. Patients with a classical clinical picture can be treated by immunization with the partner's leucocytes. The rate of success for subsequent pregnancies is about 80%. A positive effect was also observed in patients with primary infertility (about 20%).

Abortion, Habitual↗

HLA-C "blank" alleles express class I gene products. Biochemical analysis of four different HLA-C "blank" polypeptides.

Monoclonal antibodies (mAbs) W6/32, HC10, and 4E were used to precipitate class I antigens from 21 selected individuals with at least one HLA-C "blank" allele. In 19 of these individuals, characteristic HLA-C banding patterns which could be precipitated by all three HLA class I mAbs were observed on one-dimensional isoelectric focusing gels--obviously the gene products of HLA-C "blank". At least four allelic HLA-C "blank" gene products with different isoelectric points could be discerned. All of them segregated with HLA-C "blank" haplotypes in informative families; two of them were associated with HLA-B51, one with HLA-B38, and one with HLA-B18. Reactivity of the HLA-C "blank" heavy chains with mAb W6/32 indicates that they are able to associate with beta-2 microglobulin, and hence are most probably expressed at the cell surface.

Alleles↗

HLA-C locus antigens seen by one-dimensional isoelectric focusing: definition of the so far known HLA-C specificities and of two subtypes.

A panel of homozygous typing cells was employed for biochemical definition of all known HLA-C locus antigens from Cw1 through Cw11. Each HLA-C antigen yielded, after precipitation with one of the monoclonal antibodies W6/32, 4E, or HC10, a specific banding pattern on one-dimensional isoelectric focusing gels. In addition, two biochemical subtypes of Cw1 and Cw7 could be identified. These biochemical HLA-C "splits" were characterized not only by different isoelectric points but also by strong linkage disequilibriums with certain HLA-B antigens.

Antibodies, Monoclonal↗

Biochemical HLA typing: a population study in 112 Caucasians.

In order to define frequencies and associations of biochemically defined HLA-A and -B specificities and their variants and subtypes in a Caucasian population, biochemical HLA typing was performed in a panel of 112 Austrians. Already known rare variants of HLA-A2, A3, A30, Aw33 and B39 and the more frequent subtypes of HLA-B27, B35, B44 and, in addition, a so far unknown variant of HLA-B18 were present in the panel. Family segregation analyses of the biochemically defined HLA class I variants revealed that they could be found only in certain rare haplotypes, most of them in high linkage disequilibrium. The basic variant of HLA-A30, for example, obviously occurred only in the HLA-A30, B49, Cw7 haplotype, similar to the Aw33 acidic variant, which was exclusively found in the Aw33, Bw58, Cw3 haplotype. None of the biochemical variants was found in frequent common haplotypes.

Biochemistry↗

A new HLA-B antigen, BHT: definition by serological and biochemical means.

In 3 unrelated individuals, a new, so far unknown HLA-B-locus antigen was found. This HLA-B antigen, provisionally termed 'BHT', is recognized by extra reactions with alloantisera against the B5 cross-reactive group. BHT can be clearly discerned from all cross-reactive antigens by one-dimensional isoelectro focusing (1D IEF), as it reveals, on IEF gels, a characteristic, rather neutral double-banding pattern different from all known HLA class I bands. The BHT banding pattern, which is identical in all 3 BHT-positive individuals, segregates with the haplotype A28, BHT, Cw7, DRw6.

Genotype↗

[Differential effect of incompatibilities of the HLA-A and HLA-B locus on the success of corneal transplants].

The positive influence of HLA-compatible donor material on successful transplantation was proven especially for prognostically unfavourable cases. Nevertheless it is not clear whether varying importance should be attached to the antigen incompatibilities at the HLA-A and HLA-B locus. 62 keratoplasty patients, 37 of whom had primarily poor prognoses and 25 patients with low risk of transplant rejection were prospectively given transplants in which more than two certain incompatibilities at the HLA-A and HLA-B locus had been ruled out. The number of Ag incompatibilities (separately according to locus) was related retrospectively to postoperative progress. An irreversible transplant failure had occurred in 6 patients (16%) four months after surgery in the high-risk group, whereas 31 transplants (84%) remained clear. The course of healing was without complications within the first four months in all patients with favourable starting position. The influence of the HLA disparities on transplantation success was examined by means of the chi-square test. Taking the Ag incompatibilities of both loci in combination into account showed an only marginally significant (p = 0.1) influence on the survival rate of the transplant. Here HLA-A incompatibilities appear to have only secondary significance, whereas incompatibilities at the HLA-B locus correlated inversely (p = 0.02) with the success of transplantation.

Chromosome Mapping↗

A new HTC, a PLT and a PLT clone define a split of HLA-DR2 in the Austrian population.

An LD defined split of HLA-DR2, different from HLA-Dw2, Dw12 and DB9, is observed in the Austrian population. The narrow HLA-D specificity, defined by a new Austrian Homozygous Typing Cell (HTC), a primed lymphocyte (PLT) cell line and a PLT clone, is tentatively termed HLA-D"WH". Investigation of three informative families shows that HLA-D"WH" segregated together with HLA-DR2. In one family, even an individual heterozygous for HLA-DR2/Dw2 and HLA-DR2/D"WH" can be identified. A panel study including 90 non-related Austrians shows that HLA-D"WH" occurring in 6.7% of the whole panel, that is in 20% of the HLA-DR2 positive panel members, is completely included in HLA-DR2. HLA-D"WH" might be comparable to other LD specificities related to HLA-DR2, "MN2", "FJO", "AZH" or "GEN".

Austria↗

Lack of association between HLA antigens and anorexia nervosa.

Studies of the human leukocyte antigen (HLA) system were performed in 37 patients with anorexia nervosa to confirm an alleged association with HLA-B16 and haplotype HLA-A26,B38. No correlation between anorexia nervosa and HLA, including HLA-DR, could be found.

Adult↗

[Computer-assisted histocompatibility assessment in mixed lymphocyte culture (MLC)].

Analysis of the results of mixed lymphocyte culture (MLC) for compatibility testing preceding transplantation of bone marrow and other organs has so far required a vast input, both in terms of laboratory staff and work hours. We have developed a computer programme which performs this work rapidly. Graphics of the reaction patterns can be obtained, moreover, and these can prove a helpful tool in interpretation of the results.

Bone Marrow Transplantation↗

Survival and quality of life in 23 patients with severe aplastic anemia treated with bone marrow transplantation (BMT).

Survival and quality of life are reported in 23 pretransfused patients with severe aplastic anemia (SAA) who underwent bone marrow transplantation (BMT). The projected survival is 76% with 18 of 23 patients being alive 332 to 1677 days post graft (median: 842). 5 patients died between day 4 and 416. 12 of 17 patients at risk developed chronic graft versus host disease (GVH-D). 4 of these patients have a diminished quality of life due GVH-D related disabling manifestations. Autologous haemopoietic recovery was excluded in all patients by the demonstration of haemopoietic chimerism. We recommand age-adapted rejection prophylaxis; such strategy may help to diminish disabling graft versus host disease in otherwise haematologically reconstituted survivors.

Adolescent↗

HLA-D typing in Austria. A panel study using 26 newly defined homozygous typing cells.

A panel of 120 HLA-A, -B, -C and -DR typed Austrians has been typed for HLA-D by the use of 26 Homozygous Typing Cells (HTC). The new Austrian HTC, partly defined by the 9th International Histocompatibility Workshop (9WS), partly by a checkerboard experiment with internationally well defined reference HTC, type for HLA-Dw1 to -Dw7 and an obviously new, so far unknown HLA-DR2 related HLA-D determinant. Associations of HLA-DR and HLA-D antigens in Austria and their frequencies are determined. Antigen frequencies in Austria are compared to frequencies in other Caucasoid populations.

Austria↗

Another HLA-B/C recombination.

Another case of an HLA-B/HLA-C recombination is presented which shows that the locus HLA-C is situated between HLA-A and HLA-B.

Crossing Over, Genetic↗