On the mapping of PGM3 in relation to HLA.
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Biomedical subjects
Publications and source records attributed to F Kissmeyer-Nielsen.
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Some CTLs recognize HLA-structures in a different way than antibodies, i.e. they may identify other epitopes than antibodies or may define genetically distinct structures. From population studies, in vitro educated CTLs were selected giving rise to significant lysis on PHA-lymphoblasts in the absence of the sharing of HLA-A, B, (C) determinants between stimulator and target lymphocytes. Based on pair-wise correlations these CTLs form 3 clusters, identifying structures associated to HLA-markers. Subsequent testing in 14 complete families of greater than or equal to 4 children allowed the observations: (1) CML-traits assigned on the basis of single CTLs often segregated in a non-mendelian way or independent of HLA. (2) Assignment made on the basis of CTL-clusters segregated with HLA. (3) in 2 informative HLA-B/D, DR recombinant families, CML-traits segregated with HLA-B. (4) No haplotype could be assigned more than one CML-trait.
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Five hundred unrelated Danes, including 202 healthy individuals, 35 cadaveric kidney donors, and 263 patients in terminal uraemia were typed for the HLA-DR antigens DR1-w8. The HLA-DR gene frequencies of healthy Danes are in good agreement with frequencies estimated during The Eighth International Histocompatibility Workshop of the Scandinavian population, but differ to some extent from other groups of European Caucasians. This indicates geographical variation in the distribution of DR genes within Europe. Very close associations were found between the HLA-DR antigens and their corresponding HLA-D specificities, except for Dw4 and Dw6, which were included in DR4 and DRw6, respectively. Linkage disequilibrium was calculated between alleles of two loci (HLA-A, -DR; -B, -DR and -C, -DR alleles was assessed for multiple loci by using haplotype data from 32 HLA-A, -B, -C, -D, -DR, and Bf typed Danish families. The haplotype data showed that HLA-DR4 is strongly associated with HLA-B15 only in haplotypes together with HLA-Dw4. This indicates genetic heterogeneity of HLA-DR4 which, however, does not appear serologically in this study.
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HLA tissue-type antigen determination for A-, B- and C-antigens in 88 patients suffering from giant cell arteritis of the temporal artery showed no significant deviations as compared to a control material of 3164 blood donors. A weak indication of association with antigen HLA-B8 appeared to be of interest due to a corresponding indication in previous investigation. The patients were a mixed hospital material, consisting of cases of clinical temporal arteritis and patients with polymyalgia rheumatica. There was an overrepresentation of women (77%). Familial occurrence was demonstrated sporadically (3 pairs of siblings).
HLA typing was carried out in 20 psoriatics with methotrexate-induced liver cirrhosis and 44 methotrexate-treated psoriatics who at the time of investigation had not developed cirrhosis. The data were compared with results from tissue typing of 1291 healthy individuals. The antigen combination A1, B8 was found to be increased among patients with cirrhosis vis-à-vis methotrexate-treated psoriatics who did not develop liver cirrhosis. This finding is similar to data on chronic active hepatitis type A and drug-associated chronic active hepatitis. Findings of the antigen combination A1, B8 should--just as with other predisposing factors--lead to caution in liver control in psoriatics on methotrexate therapy.
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In the complement dependent lymphocytotoxic microtechnique it was found that antibody-killed frozen B lymphocytes are sufficiently stained for reliable reading after 30 min of incubation with trypan blue, while the background of staining is only about 10%. During the next 30 min of incubation, however, the background of staining increases to about 30%, whereafter it remains constant for at least 24 h. Formaldehyde is able to stop the trypan blue uptake by killed or damaged lymphocytes completely. Consequently, if formaldehyde is added to the reactions 30 min after the trypan blue addition, the otherwise rapidly increasing background of staining is kept at an acceptable level of 10%, thus making HLA-DR typing of frozen stored B lymphocytes possible. The trypan blue staining seems rather independent of incubation conditions before the addition of the dye. Similar results were obtained with T lymphocytes.
Studies of 521 sera from the Icelandic cousin marriage project were made to assess the incidence of various anti-tissue antibodies and the levels of immunoglobulins, as these were considered to be useful markers of the humoral immune response. Comparisons were made between these parameters and the HLA-A and B antigens, the blood groups, the immunoglobulin allotypes (Gm, Km and Am), the properdin factor (Bf), and other markers. These investigations offered another approach to the study of the sites of action of immune response genes in man. Because the immune response may be expected to differ for each individual and depend at least in part, on the degree of exposure to different antigens, no absolute correlation was expected. There was, however, a marked association between certain IgG anti-tissue antibodies and HLA antigens. This was most marked for HLA-A10, B18 and b27, but not for HLA-A1 or B8. The comparison of immunoglobulin levels with HLA antigens, was less striking, although HLA-A2 appeared to be associated with low levels of IgE. There were also some associations between immunoglobulin levels and ABO blood groups.
Evaluation of the results of HLA typing of 187 patients grouped into herpetic keratitis (37), non-herpetic keratitis (43), keratoconus (42), endothelial dystrophy (23), stromal dystrophy (13), lues (5), and injuries (24), failed to show convincing deviations in any of the groups from a normal control series (2900 persons). Yet, as for the herpes group, a rise in B5 must strongly be suspected. The data are presented and possible implications are discussed.
A series of 222 cases of 7 mm penetrating corneal grafts were analysed with respect to the influence of HLA compatibility. The degree of compatibility was random as no matching was done (HLA types unknown at time of operation). Consequently, most of the cases showed 3 or 4 incompatibilities. The series was divided into seven diagnostic groups (keratoconus, herpetic keratitis, non-herpetic keratitis, stromal dystrophy, endothelial dystrophy, mechanical lesion and corrosion). In all groups there was a tendency towards better results among the compatible transplantation, but only when considering the entire series could statistical significance be demonstrated. The groups of 0--2 incompatibilities showed fewer rejection episodes or opaque grafts than the groups of 3 or 4 incompatibilities (chi 2 = 9.20, P less than 0.005). Comparing only the frequency of opaque grafts among the two groups the correlation was less significant (chi 2 = 3.66, P similar to 0.05).
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