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A Svejgaard

Publications and source records attributed to A Svejgaard.

At least 271 records · Page 15Linked to original sources

Typing for HLA-D/DR associated DP-antigens with the primed lymphocyte typing (PLT) technique.

A total of 74 healthy unrelated random individuals and 36 patients with juvenile rheumatoid arthritis (JRA) were typed for HLA-D antigens with the homozygous typing cell technique and typed for HLA-D/DR associated DP-antigens with the primed lymphocyte typing (PLT) technique. All patients and some of the controls were also HLA-DR typed with a limited battery of anti-DR sera. Selected PLT-cells, specific for the HLA-D/DR antigens D/DRw1-8 and the local specificity D"H" were used. The results of the PLT-experiments were evaluated with the Normalized Median Response (NMR) method and the further procedure of DP-antigen assignment was analyzed. The DP-antigen assignments could be done solely according the NMR-values in approximately two thirds of the individuals. In the remaining individuals, further interpretation of the experimental data had to be done for the assignment of DP-antigens. The correlation coefficients were estimated between the HLA-D assignments and (i) the individual PLT-cell NMR-values with a fixed cut-off for positive reactions and (ii) the DP-antigen assignments. These coefficients were 0.79 and 0.92, respectively. The correlations between HLA-D, -DR and DP-antigen assignments of the specificities HLA-D, -DR and DP1, 2, 3, 4, 7 and 8 were analyzed in 42 controls and 36 JRA patients. The total correlation coefficients were: (i) HLA-D/DR: r = 0.78; HLA-DR/DP: 0.77; and HLA-D/DP: 0.96. The DP-antigen assignments correlated significantly better with HLA-D than with the HLA-DR antigen assignments, which does not agree with other studies. The DP-antigen frequencies among the controls were calculated and the estimated sum of gene frequency corresponding to definable DP-antigens was 0.94 indicating that about 12% of random individuals possess as yet undefined DP-antigens.

Antibody Specificity↗

A "new" primed lymphocyte typing (PLT) defined DP-antigen associated with a private HLA--DR antigen.

We have recently described a "new" private HLA-DR antigen, DR"LTM", which has a frequency of approximately 0.6% in Danes. Primed Lymphocyte Typing (PLT) cells directed towards DR"LTM"-associated determinants were generated in vitro by haplotype primings in two unrelated families with DR"LTM" positive individuals. Both PLT-cells reacted in parallel and gave positive reactions with (i) two unrelated and (ii) eight related individuals, all of whom were DR"LTM"-positive. Both PLT-cells gave negative reactions with (i) 38 unrelated and (ii) 15 related DR"LTM"-negative individuals. Thus, there was total agreement between the results obtained by HLA-DR typing with the antiserum "LTM" and by PLT-typing with these two haplotype primed PLT-cells. None of the DP"LTM"-positive individuals carried more than one of the antigens HLA-Dw/-DRw/DP1-8 and the local specificity D/DP"H". Accordingly, this "new" PLT-defined antigen, DP"LTM", most probably belongs to the series of HLA-D/DR-associated DP-antigens previously described.

Arthritis, Juvenile↗

Data reduction in HLA-D typing with the primed lymphocyte typing (PLT) technique. the normalized median response (NMR).

We describe here a simple non-parametric method for the evaluation of data obtained from primed lymphocyte typing (PLT) experiments. The method is designed to compensate for both differences in the PLT responsiveness and stimulatory capacity by a double normalization procedure based on a representative negative reaction (the median) for each PLT-cell and for each secondary stimulator. The index of response is called the Normalized Median Response (NMR). The NMR-method was developed from data from one of a series of PLT experiments aimed at HLA-D typing. The NMR-method was applied to eight other PLT experiments and was compared to two other calculation methods based on the maximal response of each PLT-cell: (i) a method without compensation for stimulator variation, and (ii) a method including non-parametric compensation for stimulator variation. The eight experiments involved 37 different PLT cells tested against 74 different stimulating cells yielding a total of 1,334 secondary combinations. The NMR-method descriminated significantly better than the other methods when the results were compared to the HLA-D types obtained with homozygous typing cell technique. In particular, the number of extra positive reactions was diminished by the NMR-method. The reproducibility and the sources of variation were studied in the eight experiments and in five additional experiments. The NMR-method reduced the combined priming-to-priming variation and day-to-day variation to a level comparable to the variation between duplicate testings of the same PLT cell tested towards the same set of secondary stimulators in the same secondary PLT experiment.

Cells, Cultured↗

Generation of HLA-D specific primed lymphocyte typing (PLT) cells and cross-reactions of PLT-cells primed with homozygous typing cells.

An approach for the selection of HLA-D specific primed lymphocyte typing (PLT) cells is described. The responder cells were primed with homozygous typing cells. Reproducible extra reactions were found and were analyzed in relation to HLA-D antigens defined by homozygous in cells (HTC's). The secondary response of 105 different PLT-cell combinations generated by 29 different primary responders against 19 different homozygous typing cells of the specificifies Dw1 to Dw8 and the local specificity "H" were tested in secondary PLT toward 17 different homozygous typing cells and 10 heterozygous cells. Cross-reactions were defined as reactions equal to or higher than the lowest HLA-D specific reaction observed. The entire experimental design and data analysis gave rise to a conservative definition of cross-reactivity. Two main groups of cross-reacting HLA-D determinants seem to exist: (i) Dwl, 3, 4, 7, and the local specificity "H", and (ii) Dw2, 5, 6, 8, and "H". The primary pairwise cross reactions were in group (i): Dw1-3, Dw1-"H", Dw3-4, Dw3-7, Dw7-"H", and in group (ii): Dw2-6, Dw2-8, Dw5-8, and Dw5-"H". The existence of such cross-reactions is likely to interfere with the results of PLT-typing and should be taken into account when attempts are made to develop HLA-D specific PLT-cells.

Cells, Cultured↗

Human leucocyte antigens in patients with alcoholic liver cirrhosis.

No significant differences in the frequencies of HLA-B8, -B40, and other HLA-A, -B, and -C phenotypes were found among patients with histologically verified alcoholic cirrhosis compared with normal controls when the p values were multiplied by the number of comparisons. This was found both in the present study of 45 patients and in the combined data of this and three other similar studies. However, these findings do not rule out that alcoholic cirrhosis might be associated with HLA factors (for example. HLA-D/DR antigens) controlling immune responses.

Adult↗

MLC compatibility, HLA-D and DR typing in cadaver kidney transplantations.

During a period of one year, spleen lymphocytes from cadaver kidney donors were cryopreserved for later investigations. The HLA-D types of 33 donors and the corresponding 39 recipients were determined in six experiments and the reactivities of the lymphocytes of the individual recipients towards those of the donors were assayed in MLC. The MLC experiments included a sufficient number of unrelated responders and stimulators to allow an estimate of the specific MLC reactivity by the stabilized relative response. A strong and significant correlation was found between specifically low reactivity of recipient lymphocytes against donor lymphocytes and graft survival. A correlation was also found between HLA-D compatibility and graft survival. DR typing was performed on the same donor-recipient pairs. In sixteen cases the DR typing of the recipients was initially a technical failure but successful when repeated on cryopreserved lymphocytes. There was a significant correlation between HLA-DR compatibility and graft survival. HLA-A, B matching and pretransplant blood transfusion did not significantly affect graft survival in this material.

Graft Survival↗

HLA studies in diabetics.

The studies of HLA in diabetes mellitus have strongly supported the subdivision into (at least) two genetically distinct groups: The juvenile onset (or perhaps better the insulin dependent) type DM, which shows a marked association to the HLA system, and the maturity onset type with a weak or no association to HLA. The HLA system has provided tools to test specific genetic models for the insulin dependent DM. A model involving one disease susceptibility locus closely linked to the HLA-loci and with a recessive susceptibility allele in linkage disequilibrium with some of the HLA factors has been proposed by others. This model cannot be totally rejected on the basis of the available data, but it is made less likely, especially because it leads to very low estimates of the penetrance which is discrepant from independent estimates, based both on studies on monozygotic twins and other families. In addition suggestive but not yet conclusive evidence of an excessive risk for HLA-Dw3/Dw4 heterozygotes is in conflict with this model.

Diabetes Mellitus↗

Basement membrane thickness, insulin antibodies and HLA-antigens in long standing insulin dependent diabetics with and without severe retinopathy.

The study was designed to show whether there was any relation between muscle capillary basement membrane thickness, HLA-antigens, anti-insulin antibodies and proliferative retinopathy. Electron microscopic measurements of muscle capillary basement membrane thickness were performed on muscle biopsies from 15 insulin-dependent diabetics and severe proliferative retinopathy, 24 insulin-dependent diabetics with minimal retinopathy and 18 age- and sex matched non-diabetics. All the patients had had diabetes for 20 years or more. None had biochemical or clinical evidence of diabetic nephropathy. Basement membrane thickness was measured according to the methods of Siperstein and Williamson. Muscle capillary basement membrane thickening occurred in 32 of 39 diabetics, using the Siperstein method, but patients with proliferative retinopathy did not exhibit thicker basement membranes than patients with no or minimal changes in the retina. There were apparent differences in HLA-antigens between diabetics with and without proliferative retinopathy, but they did not reach statistical significance. There was no correlation between muscle capillary basement membrane thickness and the quantity of insulin antibodies. The results indicate that factors other than basement membrane thickening and genetic factors in the HLA-region, are responsible for the development of proliferative retinopathy.

Adult↗

HLA types and ABO blood groups in patients with infectious mononucleosis.

Investigations of HLA and blood-groups were carried out in 68 patients with infectious mononucleosis comprising all known cases diagnosed within one year in a restricted geographical area of Denmark. The HLA distribution of these patients did not differ significantly from that of controls. Combining the results of the present investigation with two previous studies did not show any significantly different distribution from that of combined control groups. The ABO and Rhesus typing was in accordance with that found in a major Danish control group. However, available studies do not exclude the possibility that HLA-D/DR or still unknown HLA factors may be involved in the susceptibility to mononucleosis.

ABO Blood-Group System↗

The comparison between normal and Epstein-Barr virus-transformed homozygous typing cells and their use for MLC, PLT and serological detection of human Ia-type alloantigens.

Normal human lymphocytes isolated from freshly drawn blood were repeatedly stimulated (up to five times) in mixed lymphocyte cultures (MLC) with five different Epstein-Barr virus (EBV)-transformed homozygous typing cells (HTC-LCL). Each time, the same WDW-specificity was used for the restimulation. The first and the second stimulations resulted in an 2.4- to 3.1-fold increase of the original responder cell number. But after the third, fourth and fifth stimulation decreasing amounts of specifically primed lymphocytes were recovered. Primed lymphocyte typing (PLT) showed significant differences in the intensity of the stimulation depending on whether homozygous typing cells (HTC) or HTC-LCL were used as stimulators. Except for one cell type, the PLT-response was significantly stronger with HTC-LCL than with HTC. The time needed to reach the maximal PLT-response got shorter and shorter the more often the cells were reprimed by the same stimulator cell. Further differences between HTC and HTC-LCL were observed in the complement-dependent cytotoxicity assay: HTC-LCL were more sensitive towards rabbit complement and they showed an enhanced binding of anti-Ia-alloantibodies but HTC reacted more specifically with the antibodies.

B-Lymphocytes↗