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Biomedical subjects

A Svejgaard

Publications and source records attributed to A Svejgaard.

At least 253 records · Page 14Linked to original sources
PubMed1981

HLA restriction of dinitrophenyl-specific cell-mediated cytotoxicity in vitro.

Lymphocytes from dinitrochlorobenzene-sensitized individuals can be stimulated in vitro by autologous dinitrophenyl (DNP)-conjugated lymphocytes to produce cytotoxic T lymphocytes (CTLs). The activity of these CTLs is specific for DNP-conjugated target cells, and there is no cross-reaction with nitrosodimethylaniline- or trinitrophenyl-conjugated target cell. Evidence is presented which makes it improbable that the cytotoxicity is caused by an antibody-dependent (ADCC-like) mechanism. Most of the DNP-specific cytotoxicity is restricted by the HLA-ABC antigens of th CTL donor, and there is only a low degree of lysis of DNP-conjugated allogeneic target cells not sharing HLA-ABC antigens with the donor. The CTLs did not lyle non-conjugated allogeneic target cells. When CTLs were tested against allogeneic DNP-conjugated targets sharing only one of the HLA-ABC antigens of the CLT donor, it was seen that the phenomenon of preferential restriction was pronounced; that is, only some of the antigens of the donor were restricting. A certain pattern has emerged: some antigens (e.g. A2) are good restricting antigens, some (e.g. B12) do not restrict, and some (e.g. B5) function well in one donor but not in another. The serologically cross-reacting antigens A2 and A28 did not restrict mutually. HLA-C antigens may in some donors function as restricting antigens.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Association of pernicious anemia and intrinsic factor antibody with HLA-D.

One-hundred-and-six patients with pernicious anemia were HLA-A, B, C typed by serological technique and HLA-D typed by mixed lymphocyte culture technique for the specificities HLA-Dw1 - 8 and the locally defined D "H". In 13 cases, the D-typing was unsuccessful due to technical difficulties. HLA-A, B, C antigen frequencies did not show any significant deviation from expected values, while D typing showed increased frequencies of Dw2 and Dw5 and a possibly decreased frequency of Dw3. The typing was compared with clinical data such as the presence of organ specific autoimmune disease in first degree relatives, presence of anemia or myelopathy at time of diagnosis and presence of antibodies towards parietal cells or intrinsic factor. The presence of intrinsic factor antibody was associated with the presence of Dw2 and a decrease of Dw5 and possibly also with a decrease of Dw4. No associations were found for the other investigated parameters. If intrinsic factor antibodies have a pathogenetic role, our findings might reflect a heterogeneity of pernicious anemia. These findings and the recently reported association between HLA-DR5 and Hashimoto's disease link these two thyrogastric diseases together to form a special subgroup within the group of organspecific autoimmune diseases; the other diseases in the group have as a common denominator the frequent presence of D/DR3.

Anemia, Pernicious↗
PubMed1981

Technical aspects of the primed lymphocyte typing (PLT) technique.

The influence of different culture conditions in the primary and secondary cultures of the primed lymphocyte typing (PLT) technique was investigated with special reference to the discriminatory capacity of the PLT-cells generated. In the primary cultures, the maximal yield of PLT-cells was observed early (about day 7) and decreased thereafter, while the maximal specificity was obtained considerably later (about day 14). In the secondary cultures, the optimal culture time was in the interval 42 h - 72 h, and up to this culture length, gamma-irradiation (2,200-8,800 rad) of the secondary stimulators had no effect on the 14C-thymidine uptake of the cultures. In U-form microtiterplates, the number of PLT-cells per well should not be less than 2.5 X 10(4), and higher PLT-cell numbers (e.g. 5.0 X 10(4) per well) may confer further robustness upon the technique. The PLT-cell response and the discrimination was only slightly influenced by the number of secondary stimulator cells in the interval 5 X 10(4) to 2 X 10(5) cells per well. Freezing of the PLT-cells under controlled conditions resulted in a minor loss of viable eosin-excluding cells, while the specificity of the PLT-cells was unaffected. Even when the culture conditions are standardized, it is necessary to perform a normalization of the data in order to obtain reproducible results. The normalization procedure should include a compensation for the variation in (i) the general responding capacity of each PLT-cell and in (ii) the general stimulatory capacity of each secondary stimulator.

Cells, Cultured↗
PubMed1981

Correlation between HLA-D/DR associated primed lymphocyte typing (PLT) defined DP-antigens, HLA-D and HLA-DR antigens.

A panel of 79 individuals were typed for HLA-D/DR associated Primed Lymphocyte Typing (PLT) defined "DP"-antigens, HLA-D and HLA-DR antigens. Typing for DP-antigens was carried out with local PLT-cells. HLA-D and -DR typing was performed with all homozygous typing cells and all DR-antisera included in the 8th International Histocompatibility Workshop. Assignments of DP-, HLA-D- and HLA-DR-antigens were done independently and the correlations between DP/D/DR1-8 were analyzed. The panel included random unrelated individuals, and individuals previously found to have one or no identifiable HLA-D antigen (B). In the random group, 80% of the individuals were assigned to possess the same antigen with the 3 techniques, while this was only the case in 46% of B-group individuals. The overall correlation coefficients, r, for the antigens HLA-Dw/-DR/DP1-8 were 0.95 (DP/D), 0.94 (DP/DR), and 0.89 (D/DR). There is a remarkably strong correlation between HLA-D and -DR typing results concerning D/DR1-8, in particular in random individuals. It is possible to select PLT-cells that give typing results which are almost identical to those of HLA-D and -DR typing. When discrepant results were seen, HLA-DR was in general "broader" than DP which in turn was broader than HLA-D, indicating that it may be possible to split HLA-DR/DP1-8 into more "narrow" specificities.

Blood Grouping and Crossmatching↗
PubMed1981

HLA-A, B, C, D, DR antigens and primed lymphocyte typing (PLT) defined DP-antigens in juvenile chronic arthritis.

A total of 48 patients with juvenile chronic arthritis (JCA) were typed for HLA-A, -B, -C, -D and -DR antigens and 36 patients were also typed for HLA-D/DR associated "DR"-antigens with the primed lymphocyte typing technique. In the total group of patients, we found increased frequencies of HLA-B27, HLA-Dw/DP5 and HLA-Dw/DP8, and decreased frequencies of HLA-Dw/-DR/DP2. The increased frequencies of HLA-Dw/DP8 and the decreased frequencies of HLA-Dw/-DR/DP2 were primarily found among patients with persistent pauciarticular arthritis. The frequencies of HLA-Dw/-DR/DP4 were increased in patients with polyarticular arthritis. The frequencies of HLA-B27 and -Dw/DP5 were increased in both pauciarticular and polyarticular arthritis. The results indicate (i) that genetic factors controlled by HLA confer susceptibility and/or resistance to JCA, and (ii) that the clinical subdivision of JCA into pauciarticular and polyarticular JCA can be supported by the presence of different genetic markers (HLA-antigens) in the two groups of JCA-patients. If these data can be confirmed HLA-D, -DR or DP typing may be of value in the prognostic evaluation of patients with pauciarticular onset JCA.

Antigens, Surface↗
PubMed1981

HLA-DR phenotype and HLA-B,DR haplotype frequencies in 704 unrelated Danes.

HLA-ABC and DR antigens were studied in 704 unrelated Danes (84 cadaver kidney donors, 307 healthy individuals, and 313 uremic patients), HLA-DR1, 2, 3, 4, 7, w8, and w10 were investigated in all individuals, whereas DR5, "DRw6", and w9 were only studied in parts of the material. The frequencies of DR1, 2, 3, 4, 5, and w10 were similar in the three groups, while those of "DRw6", DR7 and w8 differed significantly. The deviation of the DR7 frequency was small and probably due to change; "DRw6" is considered difficult to define, and DRw8 may have been difficult to define in the early part of the material. DR-phenotype distributions showed perfect fits to Hardy-Weinberg expectations for the three groups separately and for the combined group. When our combined DR antigen frequencies were compared with those from another Danish sample (Madsen et al, 1981), significant differences were found for "DRw6", w8 and w10. However, in general, the same HLA-B,DR phenotype combinations showed significant positive associations in the two samples, and most of the corresponding haplotype frequencies and delta values were quite similar.

Denmark↗
PubMed1981

HLA genotype distribution and genetic models of insulin-dependent diabetes mellitus.

When comparing the odds ratios (OR's) obtained by contrasting various HLA-DR phenotypic classes in patients (e.g. diabetics) and controls, it is desirable to use the same reference phenotypes for all OR's. If this is done, it can be shown that the OR for, say, DR3/4, heterozygotes cannot exceed the OR's for both of the two homozygotes (DR3/3 and DR4/4), if there is one disease susceptibility locus with one normal allele and one susceptibility allele in linkage disequilibrium with two HLA-DR alleles (HLA-DR3 and 4) and if the action of the susceptibility gene is dominant, recessive or intermediate between dominant and recessive. In each of these cases, the OR for the heterozygotes will be intermediate between the OR's of the two homozygotes. If the two alleles at the susceptibility locus act in an overdominant way, the OR for the heterozygotes may in some cases exceed the OR's of both homozygotes. Comparison of the magnitude of two OR-values can be reduced to investigating whether the OR value generated by comparing one phenotypic class against the other (as reference group) differs from unity. There is suggestive but not conclusive evidence that the OR of developing insulin-dependent diabetes for the DR3/4 genotype is higher than the corresponding OR-values for both of the two homozygotes (DR3/3 and DR4/4), indicating that the susceptibility to this disease may not be explained by a dominant, recessive or intermediate model.

Diabetes Mellitus↗
PubMed1981

General paralysis of the insane associated with HLA-Aw32.

HLA-A, -B, and -C locus antigens were determined in 35 unrelated patients with general paralysis of the insane (GPI), and in 13 neurosyphilis patients without dementia. HLA-Aw32 was found more frequently (corrected p = 4.9 x 10(-2) in the GPI patients than in 1009 controls. None of the patients having neurosyphilis without dementia had HLA-Aw32. These findings indicate that genetically determined mechanisms may play a role in development of GPI. Further studies of such rare patients should be initiated to investigate whether these observations reflects a true association or whether they are due to chance. If possible other well defined groups of tertiary syphilis should also be studied.

Adult↗
PubMed1981

HLA-D antigen frequencies in Sjögren's syndrome. Differences between the primary and secondary form.

HLA-A, B, C and D typing was performed in 19 patients with primary Sjögren's syndrome (primary SS) and in 15 patients with rheumatoid arthritis (RA) and secondary Sjögren's syndrome (RA-SS). In the primary SS group, the frequency of HLA-Dw2 was increased (p less than 0.01; "corrected" p greater than 0.05) while the frequency of Dw3 was non-significantly increased. In the RA-SS patients, the frequency of HLA-Dw4 was increased to 84.6% (relative risk = 22.8; p less than 0.001) and the frequency of Dw2 was non-significantly decreased. An increased frequency of Dw2 in primary SS has not been reported before. To investigate if this observation was due to chance, a new series of 16 patients with primary SS were HLA typed. In this new group, the frequencies of both Dw2 and Dw3 were significantly increased, while the frequency of Dw4 was significantly decreased. In the whole group of primary SS patients, the frequencies of Dw2 were 56.3% (relative risk = 3.7; p less than 0.001). Dw3:50.0% (relative risk = 2.8; p less than 0.01) and Dw4: 6.3% (relative risk = 0.28; p less than 0.05). We conclude that genetic factors associated with the HLA-system are involved in the development of Sjögren's syndrome and that these genetic factors are different in primary and secondary Sjögren's syndrome. In primary Sjögren's syndrome, the association with both Dw2 and Dw3 might suggest a further heterogeneity of the syndrome.

Arthritis, Rheumatoid↗
PubMed1981

HLA-DR typing in cadaver kidney donors and recipients in Copenhagen.

Among 224 cadaver kidney transplantations performed since Spring 1977, successful DR typing of both donor and recipient could be done in 149 cases. Assessment of DR match grade and clinical data was done independently. The minimum observation time was 3 months and the time of follow up was 1 December, 1980. There was an effect of DR matching which became significant when only 1. transplants were considered and high risk recipients (i.e. diabetics) excluded. Transfusions were of minor importance on graft survival and the difference was only obvious in the first year after transplantation. Matching for HLA-A, B antigen had no obvious effect on graft survival in this material.

Blood Transfusion↗
PubMed1981

Autoantibodies, histocompatibility antigens and testosterone in males with alcoholic liver cirrhosis.

Titres and immunoglobulin classes of autoantibodies were examined in 69 male patients with alcoholic liver cirrhosis and the findings were related to particular human leucocyte antigens and serum concentration of testosterone. Both anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA) were significantly more prevalent in patients with cirrhosis than in sex- and age-matched controls. Antimitochondrial antibodies and liver cell membrane antibody were found in 4% of the patients, and in none of the controls, but this difference was not significant. Patients with HLA-B8 and/or HLA-B12 had higher titres of ANA (n.s.) and SMA (P less than 0.05) than patients without these HLA antigens. Serum concentrations of testosterone were significantly lower in ANA-positive patients than in those negative (P less than 0.05), and a similar tendency was found in SMA-positive patients. With increasing titres of ANA the concentration of testosterone fell. Serum concentration of testosterone correlated inversely (P less than 0.05) with plasma immunoglobulin G and A. It is concluded that both genetic and hormonal factors may influence the humoral immune response in these patients.

Adult↗
PubMed1981

A review of HLA antigens in longstanding IDDM with and without severe retinopathy.

The hitherto published studies of HLA antigens in diabetic retinopathy are reviewed. The existence of HLA associated genes conferring susceptibility (or resistance) to the development of diabetic retinopathy has neither been proved nor ruled out. Possible explanations of the lack of unanimous conclusions are discussed. Further studies in caucasians and other ethnic groups are warranted: future studies should be internationally accepted, well-defined diagnostic criteria and classifications of diabetes and diabetic retinopathy, and study and control groups should be carefully matched for other genetic and nongenetic risk factors. Future studies should include HLA D/DR typing.

Diabetes Mellitus↗
PubMed1980

HLA-D restriction of the proliferative response to hapten dinitrophenyl-conjugated cells. I. No indication of cross-reaction between dinitrophenyl-conjugated autologous and nonconjugated allogeneic cells.

Evidence is presented in humans that the dinitrophenylated (DNP) antigen, previously shown to be restricted in cell-mediated cytotoxic assays by the HLA-A and -B antigens, is restricted in the proliferative response by HLA-D antigens. A gene dose effect was observed. Some influence of DNP conjugation on the mixed lymphocyte culture stimulatory capacity is shown, but the restriction phenomenon is obvious with the degree of conjugation chosen. The functional part of HLA-D is more likely to follow DR than D antigens. Unspecific conditioning of alloreactivity in secondary cultures is shown by negative as well as by positive selection procedures to be different from the major part of the DNP-specific clones.

Cross Reactions↗