HLA and disease associations with special reference to mechanisms.
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Complement C2↗
Biomedical subjects
N Morling
Publications and source records attributed to N Morling.
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↗
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↗
[Severe combined immunodeficiency. Successful bone marrow transplantation from father to child].
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Adult↗
HLA--Dw4 and rheumatoid arthritis.
Forty-seven patients with a "definite" or "classical" rheumatoid arthritis according to the ARA criteria were typed for the serologically detectable HLA--A, --B, and --C antigens and 36 of these patients were typed for the HLA--D antigens, Dw1, 2, 3, 4, 6, 7, and 8 by the MLC technique. The frequency of Dw4 was increased to 44.4% in the patients compared to 17.2% in normal controls (P = 8 X 10(-4)). The frequency of Dw1 and Dw7 was also increased although this was only of borderline significance. The frequency of Dw2 was remarkably low, especially in females, which is of interest, as the same antigen has a low frequency in some other autoimmune diseases. No significant deviations of the frequencies of HLA--A, --B, and --C antigens were found in rheumatoid arthritis patients.
Adult↗
HLA and disease.
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Adrenal Hyperplasia, Congenital↗
Successful nonsibling bone marrow transplantation in severe combined immunodeficiency.
Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA-A antigen but was HLA-Dw2 homozygous like the patient; his lymphocytes showed a slight response to the patient's cells in mixed lymphocyte culture (MLC). At the age of 2 1/2 months and again at 5 months, she was given a bone marrow transplant from the father. During the entire course the patient had no infections, and apart from a transient eosinophilia she had no signs of graft-versus-host reaction. Immunological reconstitution was nearly complete at 9 months of age, when she was recontaminated. One year later plasma immunoglobulin concentrations are in the low normal range (IgG and IgM) or decreased (IgA); tests of cell-mediated immunity are normal. Apart from slight upper respiratory infections, the patient has been healthy. Physical and psychological development have been normal.
Bone Marrow Transplantation↗
Post-transfusion purpura treated with plasma exchange by haemonetics cell separator. A case report.
A case of post-transfusion purpura in a 61-year-old, multiparous female with a platelet alloantibody (anti-Zwa) in her serum is reported. The patient was successfully treated with plasma exchange by means of a Haemonetics 30 cell separator and corticosteroids. Compared with other therapeutic measures, plasma exchange seems to shorten the duration of thrombocytopenia. Major surgery was possible in our patient within ten days of development of the syndrome.
Appendectomy↗
Iron stores in blood donors evaluated by serum ferritin.
Male and female blood donors were grouped according to their blood donations, and the iron stores were estimated by a two-site immunoradiometric assay for ferritin. Hb serum iron, serum transferrin and transferrin saturation were also measured. A remarkable low serum ferritin concentration was found in male donors, who had donated blood one or two times. This might indicate that the serum ferritin concentration in male blood donors is not linearly correlated to the iron stores. Among 30 female donors 14 had ferritin values below 10 ng/ml, which have been shown to be indicative of iron deficiency. The serum ferritin concentration could not be used to predict the donors who developed low Hb values by the blood donation which followed. Serum ferritin was correlated to serum iron in men and to serum transferrin and transferrin saturation in both men and women.
Adolescent↗
C3 polymorphism in a Danish cystic fibrosis population and its possible association with antibody response.
The C3 types of human serum are reported for a material of 113 Danish cystic fibrosis patients, age 0-30 years. The frequency of the C3F gene was 0.2832 which was significantly higher (p less than 0.0005) than the frequency found in a control group of 224 healthy babies (C3F = 0.1585). It also differed significantly (p less than 0.01) from the C3F gene frequency of 0.1780 found in 177 blood donors, age 20-24 years. A significant association between any of the C3 phenotypes and the most serious infection in cystic fibrosis, chronic mucoid P. aeruginosa infection, or the antibody response against these bacteria was not found.
Adolescent↗
Lymphocyte unresponsiveness to mitogens in vitro is not equivalent with severe immunodeficiency.
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Adolescent↗
Lymphocyte transformation induced by nickel sulphate: an in vitro study of subjects with and without a positive nickel patch test.
Lymphocytes from 8 patients with contact dermatitis and a positive nickel patch test, 7 patients with contact dermatitis due to other factors and with a negative nickel patch test, and 9 other subjects, 7 of whom suffered from other dermatological disorders, were tested with the lymphocyte transformation test (LTT), using nickel sulphate in various concentrations. All execpt one of the nickel allergics showed a significant response to nickel, whereas the controls showed borderline (3 patients) or no response (12 patients). These observations confirm previous findings indicating that nickel hypersensitivity can be diagnosed in vitro. This may be of importance in cases of acute contact dermatitis where patch testing is undesirable. Some individuals with a negative nickel patch test responded significantly though weakly to nickel in the LTT, indicating that apart from acting as a specific antigen (hapten?) nickel sulphate may also have weak non-specific mitogenic properties.
Allergens↗
Immunological in vitro parameters in patients with multiple sclerosis and in normal individuals.
The general immunological capacity of 40 patients with multiple sclerosis has been evaluated with lymphocyte transformation test including both mitogens (PHA and PWM) and antigens (PPD, Candida albicans, Staph. aureus and E. coli). Determination of T and B cells was performed by E-, EAC-rosetting and immunofluorescence for surface immunoglobulins. Compared with the results obtained in 42 normal individuals only minor differences were found.
Adult↗
Lymphocyte transformation in vitro in dermatophytosis.
Peripheral blood lymphocytes from 59 patients with dermatophytosis and from nine young healthy women were studied by the lymphocyte transformation test (LT) using mitogens and bacterial as well as fungal antigens. The latter included Candida albicans (CA) and four dermatophyte species, viz. Trichophyton rubrum (TR), Trichophyton mentagrophytes (TM), Epidermophyton floccosum (EF) and Microsporum canis (MF). Most of the patients showed normal transformation in response to mitogens and non-dermatophyte antigens, indicating that they have no functional T-cell deficiency. Dermatophyte antigens act as stimulators in LT. In general, patient lymphocytes responded more strongly to these antigens than lymphocytes from controls. In most patients suffering from TM infections, response to the TM antigen was significantly stronger (p less than 0.05) than that in the other patients, indicating that this antigen preparation shows species specificity. In patients with Trichophyton (TR + TM) infections, response to the corresponding antigens was significantly stronger than that in the other patients, which suggests the existence of genus specificity. Any differences between patients suffering from chronic TR infections and those with acute TR infections were not observed, a finding which is in contrast to those obtained in other studies. However, a few patients with chronic TM infections responded weakly to mitogens and non-dermatophyte antigens. LT in four patients with id-reaction to TM infection was not found to differ from that in the remaining TM patients.
Antigens, Bacterial↗
Specific lack of responsiveness to certain HLA-D (MLC) determinants with notes on primed lymphocyte typing (PLT).
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Adult↗