Search PubMed⌕ Search

Biomedical subjects

A Svejgaard

Publications and source records attributed to A Svejgaard.

At least 235 records · Page 13Linked to original sources
PubMed1983

Heterozygous expression of insulin-dependent diabetes mellitus (IDDM) determinants in the HLA system.

HLA phenotypes of cases with insulin-dependent diabetes mellitus (IDDM) and identity by descent of HLA haplotypes in affected sib-pairs support an intermediate model in which morbid risk is increased by one HLA-linked IDDM determinant, and greatly increased by two determinants, which may be qualitatively different in DR3 and DR4 haplotypes. Linkage analysis allowing for gametic disequilibrium reveals no recombination in pedigrees with a DR3/DR4 propositus, but spurious recombination in the remaining pedigrees. This evidence favors interaction of unlinked IDDM determinants to produce affection in a small proportion of heterozygotes for an HLA-linked determinant. Partition of data by HLA type of the propositus (ideally by DR and the complement types jointly) is a powerful method to resolve etiological heterogeneity for HLA-associated diseases.

Adult↗
PubMed1982

Followup study on patients with Reiter's disease and reactive arthritis, with special reference to HLA-B27.

An analysis of 160 patients with Reiter's disease, 144 with yersinia arthritis, and 9 with salmonella arthritis was performed, Complete or incomplete Reiter's syndrome was observed in one-third of the patients with yersinia arthritis and in most of those with salmonella arthritis. During the followup period, chronic back pain and joint symptoms were frequent in all the patient groups. Patients who were HLA-B27 positive had a more severe acute disease (more frequent back pain, urologic symptoms, mucocutaneous manifestations, and a longer duration of the disease) and more frequent chronic back pain and sacroiliitis.

Adolescent↗
PubMed1982

Concanavalin-A-activated suppressor cells in patients with juvenile rheumatoid arthritis.

Concanavalin-A-induced suppressor cell activity was investigated in 63 patients with a definite diagnosis of juvenile rheumatoid arthritis. Peripheral blood lymphoid cells from these patients did not have the same ability as cells from normal individuals to suppress the proliferative response of autologous cells, responding to phytohaemaglutinin, Candida albicans antigen, or allogeneic cells. No correlation was found between suppressor activity, disease activity, or number of joints involved. Nor was there any significant association between decreased suppressor cell activity and HLA-A, -B, -C, -D antigens, although there was a tendency towards association between decreased suppressor cell activity and HLA-B27.

Adolescent↗
PubMed1982

Frequency of nine HLA-D antigens in the Danish population.

The frequency of HLA-Dw1-8 and DH was determined in 389 unrelated healthy Danes and in 257 kidney patients. All individuals were HLA-A, B, C typed, 168 of the normal individuals and all kidney patients were typed for HLA-DR. The frequency of Dw1-8 in the normal material and kidney patient material was quite similar except for Dw6, which showed an increased frequency among the kidney patients, but as the patients are not prospectively ascertained, the significance of this finding is unclear. The frequency of the blank allele is 0.19 which is comparable to other Scandinavian materials but much lower than that seen in the joint report of the 8th International Histocompatibility Workshop. The D frequencies correlate quite well with the HLA-DR frequencies, the biggest discrepancy between D and DR exists for D/DR4, where DR4 is much "broader". The DR4 positives can be divided into the Dw4 positives, strongly associated with B15 and the Dw4 negatives, not associated with B15 but with B40. Primed lymphocyte typing in some cases followed HLA-DR, in other cases HLA-D assignment. For HLA-D/DR2 the DR assignment also seemed to be broader, the DR2 positive, Dw2 negative group not being associated with B7, but possibly with B5. In the assignment of HLA-D determinants, "false negatives" have caused problems in many materials, but the inclusion of a number of known control responders in our experiments has made it possible to increase the accuracy of assignment by adjusting the cut-off level for typing responses according to the typings of the controls.

Denmark↗
PubMed1982

Genetic studies of insulin-dependent diabetes mellitus: segregation and linkage analyses.

The inclusion of HLA data in genetic studies of insulin-dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. As a new approach, we first applied complex segregation analysis, independently of HLA data, to two combined Danish family materials. Then the best fitting segregation model was entered into linkage analysis of a third material, including family as well as HLA data. The best solution obtained in the segregation analysis was a mixed model, including an intermediate gene, which on the penetrance scale acts as a recessive, together with a polygenic component. The linkage analysis showed an overall recombination fraction of 0.0417 with high coupling frequencies for the HLA-DR3 and HLA-DR4 alleles and the putative disease susceptibility gene. However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA-phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA-DR3/DR4 pedigrees and the remaining pedigrees, respectively. In total, we found convincing evidence that two familial factors contribute to IDDM: a locus within HLA, which very well may be DR; and an unlinked mechanism which is unimportant for HLA-DR3/DR4 but simulates recombination. If confirmed, this conclusion has important implications for further genetic studies of IDDM and complex segregation analyses of family materials sampled according to criteria which include HLA data of the probands are highly needed.

Adolescent↗
PubMed1982

Congenital primary hypothyroidism and HLA.

Previous studies have suggested an association between congenital hypothyroidism and HLA-Aw24 or B18 antigens. The frequencies of HLA-A, B and C antigens were studied in 33 unrelated Danish patients with congenital hypothyroidism (5 with aplasia of the thyroid gland, 16 with ectopic thyroids and 8 with thyroid dyshormonogenesis). HLA-Aw24 only appeared in patients with ectopic thyroids and HLA-B18 was only seen in patients with dyshormonogenesis. However, the frequencies of HLA antigens in patients and in a large number of controls did not differ statistically significantly. We conclude that HLA typing is without any predictive value in determining the risk of developing or giving birth to a child with congenital hypothyroidism.

Child, Preschool↗
PubMed1982

Heterozygotes and cryptic patients in families of patients with congenital adrenal hyperplasia (21-hydroxylase deficiency). HLA and glyoxalase I typing and hormonal studies.

In a group of 18 unrelated Danish children with 21-hydroxylase deficiency (21-OH def.), human leukocyte antigen (HLA) typing revealed a significant increase of Bw47 and a significant decrease of B8. HLA studies of the families of 14 probands predicted among the siblings 11 heterozygote carriers and 3 genetically unaffected. Glyoxalase studies showed a recombination fraction of 8%. ACTH-stimulated 17-OH progesterone is the only hormone value useful in the discrimination between heterozygotes and normals. Two families are described in detail. In one family, one of two HLA-identical brothers had classical virilizing congenital adrenal hyperplasia (CAH), while the other was a normal boy without 21-OH def. In another family with 3 girls, one had classical, salt-wasting CAH, one had "late onset' CAH, and the third sister and the father shared the HLA-B14 antigen and were shown to have "cryptic' 21-OH def.

Adolescent↗
PubMed1982

T cell clones restricted to "hybrid" HLA-D antigens?

The genetics of T lymphocyte/accessory cell interactions were studied by using antigen-specific monoclonal T cell lines from human peripheral blood and X-irradiated non-T cells (E rosette-depleted) as accessory cells. The T cell lines were obtained by expanding single colonies from soft agar-cloned E rosette-positive lymphocytes, previously incubated for 3 days in liquid culture with 30% autologous X-irradiated non-T cells and antigen (PPD). When investigated with both autologous and allogeneic accessory cells of various HLA-D genotype, different sets of PPD-specific T cell lines were obtained from HLA-D heterozygous individuals; two sets restricted to each one of the two HLA-D antigens, and a third set responding to PPD only when presented by accessory cells carrying both HLA-D antigens possessed by the T cell donor. A few cell lines responded to PPD only in the presence of autologous accessory cells.

Clone Cells↗
PubMed1982

HLA and diabetes.

HLA studies have conclusively demonstrated that IDDM and non-IDDM are separate disease entities. A considerable part of the genetic susceptibility to IDDM is due to one or more HLA genes. The HLA-DR3 and -DR4 factors showing the strongest association with IDDM belong to the so-called DR antigens, which are believed to be the immune response determinants of man. A dominant model for the HLA-controlled susceptibility to IDDM has been ruled out and a recessive model seems unlikely. A gene-dose model intermediate between dominance and recessivity is still possible, but there is also some evidence against this model, because DR3/4 heterozygotes seem to have a considerably higher risk of developing IDDM than has DR3/3 and DR4/4 homozygotes. It has been suggested that DR3 (or a DR3-associated factor) and DR4 (or a DR4-associated factor) confer susceptibility to IDDM each by a separate mechanism, and more recently that DR3/4 heterozygotes may carry combinatorial antigens which could contribute to the susceptibility to IDDM. Studies of HLA-associated clinical heterogeneity within IDDM are indicated to gain further insight in the genetics of IDDM.

Diabetes Mellitus↗
PubMed1981

HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus.

Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n = 164), and a subset (n = 93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR+ was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.

Diabetes Mellitus↗
PubMed1981

Typing for human alloantigens with the primed lymphocyte typing (PLT) technique with notes on the interpretation of PLT data.

A typing system for HLA-D/DR-associated PLT-defined determinants, which have been called "DP" antigens, is reported. Some of the results concerning a data interpretation system, the reproducibility of PLT results, and the correlations between the results of HLA-D, -DR, and DP typing are presented. Also, a "new" human alloantigen, EP1, not belonging to the series of DP antigens, is defined with PLT.

Epitopes↗
PubMed1981

In vitro susceptibilities of normal human skin fibroblasts to oncoviruses, and the decreased susceptibility to HSV of fibroblasts from untreated Hodgkin's patients.

Fibroblast cultures established from the skin of 56 healthy controls and 15 untreated Stages I and II Hodgkin's patients (HD) were studied in their 3rd, 4th and 5th in vitro passage with respect to transformation with Simian sarcoma virus (SSV) and SV40 and with respect to replication of herpes simplex virus (HSV) Types 1 and 2, pox virus and interferon release. Susceptibility to the 5 viruses varied independently, except for an inverse correlation between susceptibility to SSV and HSV. HD cultures showed a depressed replication of both types of HSV. There was a borderline (P = 0.02) correlation between magnitude of HSV replication and presence of HL-A type B-w44, but this does not explain the HD control difference. Furthermore, the level of serum antibodies to HSV common antigen was not related to magnitude of in vitro replication. The results thus speak against generally enhanced cellular susceptibility to HSV as a reason for the high titres of serum antibodies to HSV in HD patients.

Adolescent↗
PubMed1981

Concanavalin-A-induced suppressor lymphocytes in normal individuals.

Suppressor lymphocytes are now known to play an important role in the control of immune responses. It has been demonstrated that lymphocytes stimulated by the mitogen concanavalin A (Con A) have the ability to suppress the normal lymphocyte response to antigens. It has further been shown that this suppressive action is reduced when the suppressing lymphocytes are derived from patients with disorders (e.g. systemic lupus erythematosus) in which it has been suggested that suppressor cell function is abnormal. In this study we have examined several aspects of the Con A-induced suppression. The induction of suppression required viable cells, and both the induction and the action of the suppressor cells were radio-resistant. The induction of suppressor cells by Con A was independent of DNA synthesis but not of protein synthesis. The action of these suppressor cells was enhanced by the addition of prednisolone to the cultures. This latter observation is of interest in view of the action of steroids in diseases in which a defect of suppressor cells is suggested to be present and lends support to the importance of suppressor cells in the aetiology of these disorders.

Cell Survival↗