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Biomedical subjects

N Morling

Publications and source records attributed to N Morling.

At least 109 records · Page 6Linked to original sources
PubMed1985

HLA antigen frequencies in juvenile chronic arthritis.

HLA-A, B, C, D, and DR typing was performed in 104 patients with Juvenile Chronic Arthritis (JCA). The majority of these (88 patients) participated in a follow-up study of a series of consecutive patients including patients in remission. The study confirmed that JCA is positively associated with B27, Dw8, and possibly Dw5, and negatively associated with Dw2 and Dw7. In JCA patients in remission, the frequency of Dw4 was significantly decreased to 5.0%, compared with 25.0% in healthy Danes and 23.7% in JCA patients with active disease. In pauciarticular onset JCA, the frequency of Dw4 was significantly decreased to 8.1% compared with 25.0% both in controls and in polyarticular onset JCA. These data indicate that Dw4 may be a risk factor of chronicity and multiple joint involvement in JCA. Chronic iritis was present in 18.2% of Dw8-positive patients, compared with 7.0% in Dw8-negative patients, and the frequency of Dw8 was 50.0% in JCA patients with chronic iritis. Thus, Dw8 may be a risk factor of chronic iritis in JCA. Genetically, three distinct subgroups seem to exist: (i) a B27-associated group; (ii) a D/DR5- and D/DRw8-associated group, and (iii) a D/DR4-associated group.

Adolescent↗
PubMed1985

HLA-B27 in juvenile chronic arthritis.

The prevalence of HLA-B27 in 88 patients with juvenile chronic arthritis was 22/88 (25%) with little variation among the 3 commonly recognized onset types. This was significantly more frequent than the prevalence of 9.4% in a Danish reference population. A strong association was found between the HLA-B27 antigen and 3 subgroups of patients: (1) boys with pauciarticular and late onset disease; (2) girls with apophyseal joint fusion; (3) a group of patients in whom the clinical picture was compatible with reactive arthritis or incomplete Reiter's syndrome. When these 3 subgroups were excluded from the total patient population, only 8 of the remaining 63 patients carried the B27 antigen, i.e., 13%, which was not significantly different from the prevalence in the reference population. Thus, the 3 subgroups account completely for the increase of B27 in the entire group of patients.

Adolescent↗
PubMed1983

Stimulation in primary MLR caused by a PLT defined non-HLA-D/DR determinant, EP1.

The influence in primary mixed lymphocyte culture reaction (MLR) of a primed lymphocyte typing (PLT) defined non-HLA-D/DR determinant, EP1, was investigated. In primary MLR between HLA-D/DR compatible lymphocytes, the response of the lymphocytes from 14 EP1-negative HLA-D/DR heterozygous individuals towards two EP1-positive homozygous typing cells (HTCs) was on an average approximately 35% higher than the response towards two EP1-negative HTCs (P less than 0.01). The strength of the MLR between lymphocytes from 25 EP1-negative and 10 EP1-positive individuals matched for two HLA-D/DR antigens was investigated. The average responses of EP1-negative lymphocytes against EP1-positive lymphocytes were approximately 40% higher than the average responses against EP1-negative lymphocytes (P less than 0.01). These data indicate that the PLT defined determinant EP1 causes stimulation in primary MLR.

Epitopes↗
PubMed1983

Intra HLA-D/DR region recombinant detected by primed lymphocyte typing (PLT).

The chromosome 6 markers, HLA-ABC, D, DR, MT, properdin factor Bf, and complement factors 2 (C2) and 5 (C4), were studied in three families, each of which included two HLA identical siblings, one or both of whom were known to be HLA-B: GLO recombinants. The families were also typed with primed lymphocyte typing (PLT) for HLA-D/DR region associated DP antigens. None of these studies gave evidence that the recombinations had occurred within the HLA region. Mixed leucocyte culture (MLC) tests within the families showed no detectable stimulation between the HLA identical siblings in two of the families, but a very weak stimulation between the HLA identical siblings (H and G) in the third family (GG). No reactive PLT reagents were generated when cells from the HLA identical siblings of the first two families were primed against each other. In contrast, priming between cells of H and G gave rise to reactive reagents. One of these (GHx), reacted with a determinant which segregated within the GG family as if child G was a paternal recombinant between the HLA-D, DR, DP, and C4 loci, on the one hand, and on the other hand one or more loci governing other HLA-D/DR region controlled lymphocyte activating determinants. This reagent was only restimulated by cells from two of 47 unrelated individuals. The other PLT reagent (HGx) did not give a clearcut pattern within the family because it was weakly positive with all family members (most of whom were D/DR2-positive) except the specific responder; in the panel it reacted with a determinant significantly associated with D/DR/DP2. Other PLT reagents could be generated within the family against lymphocyte activating determinants controlled by genes in the two paternal haplotypes telomeric to the assumed recombinational site. These reagents gave stronger reactions than the HGx and GHx reagents and reacted with two determinants in the unrelated panel strongly associated with D/DR/DP2 and D/DR/DP6, respectively. It seems likely that the GG family represents a third example of a recombination between the HLA-DR and SB loci. Our findings further support the assumption that the DR determinants may be immunodominant in lymphocyte activation.

Chromosomes, Human, 6-12 and X↗
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↗
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

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-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

In vitro nickel binding to mononuclear cells in peripheral blood.

Mononuclear cells from the peripheral blood of four nickel-sensitive persons and 4 controls bound equal amounts of 63 nickel in vitro. 90--99% (mean 96%) of the 63 nickel was removed from the cells by washing three times every 30 minutes for 120 minutes. For 4 other patients and 4 controls, lymphocyte transformation with autologous nickel-incubated, irradiated cells as the stimulant showed that nickel was bound to the cells in sufficient quantities and was present in a form which could induce lymphocyte transformation in vitro in nickel-sensitive patients.

Dermatitis, Contact↗
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↗