HLA class II antigens in endogenous psychoses.
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Biomedical subjects
Publications and source records attributed to R Wank.
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The key role of HLA polymorphism in the pathogenesis of many diseases and in determining compatibility in transplantation makes it desirable to employ automated systems for identifying HLA polymorphism. For more than one year we have used the photometer system Patimed commercially available from the Leica company. We compared the results of the conventional cell-mediated lympholysis test and conventional serological HLA typing with the results obtained by the Patimed system. Despite some good preliminary results it would be premature, in our opinion, to recommend the Patimed system for routine assessment of killer cell activity whereas we can definitely recommend the Patimed system to define HLA class I and class II molecules serologically for research or routine purposes.
HLA molecules serve as identity markers for immunocompetent cells which respond to pathogens and transplant tissue antigens to distinguish self from non-self. The continuous discovery of new HLA polymorphisms which are associated with various diseases or are involved in graft rejection continuously increases the number of HLA antigens which need to be identified for each individual. We defined the HLA class I and HLA class II antigens with the NIH standard microcytotoxicity system and compared the results with those obtained using the commercially available automated Patimed system. Our results show that serological identification of HLA antigens with the Patimed system is reliable. It can be recommended for routine as well as for research purposes.
Many immune responses are controlled by genes of the major histocompatibility complex (MHC). In man these include the loci encoding the HLA-A, -B, -C, -DR, -DQ and -DP antigens, and many diseases have been linked with these. But attempts to identify HLA genes in man that might explain why an immune response against malignant tumours should be ineffective have so far been disappointing, apart from the association reported between the HLA-DR1 antigen and a susceptibility to a rare carcinoma of the thyroid gland. Here we describe another strong connection between a common malignant tumour and an HLA antigen, namely between HLA-DQw3 and squamous cell carcinoma of the cervix: from the 1988 United States tumour registry, 1 in every 63 newborn girls will develop this invasive cancer. We found that 88% of 66 patients had the leukocyte antigen HLA-DQw3 when it would normally be expected in only 50% of individuals. In animals the immune system and the MHC act in defence against virally induced tumours, but until now there has been no evidence that they do so in humans: as squamous cell carcinoma is probably virally induced, our discovery of its association with an HLA antigen will be important to the understanding of the immunogenetic basis of a susceptibility to this tumour.
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In a 41-year-old VII-gravida, I-para, the husband's reciprocal translocation of the chromosomes 1 and 18 as well as a partial identity of the marital partner in the HLA-system may have been the underlying causes for five abortions. In the 7th pregnancy, a prenatal chromosome analysis was performed as well as an immunotherapy with paternal lymphocytes, when uterine bleeding occurred. After termination of bleeding, the pregnancy continued without any complication. Our case report demonstrates the importance of an extensive search for causes leading to recurrent abortions not only with regard to diagnosis but also with regard to therapy in pregnancy.
In most centers allogeneic bone marrow transplantation is restricted to patients with HLA-identical siblings as donors. We have transplanted 16 patients with marrow of donors other than HLA-identical siblings. Seven patients were grafted in the years 1978 until 1984. Six died of transplant complications and one of recurrent leukemia. More recently 9 patients were transplanted following an improved immunosuppressive conditioning treatment derived from experimental studies in dogs. Four are alive and in continuous remission between more than 2 months and 2 years. 5 patients died, 3 from fungal infections, one from recurrent leukaemia and one early from endothelial leakage syndrome. Our results indicate that intensified immunosuppressive conditioning may improve the results of marrow transplantation from HLA-haploidentical donors.
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We studied the genetic markers in human leukocyte antigen (HLA) region HLA-A, -B, -C, -DR, -DQ, C2, Bf, C4A, and C4B of 31 patients with erythema multiforme (EM) and their families. In contrast to the complement allotypes, which showed no deviation from the distribution in the normal population, two HLA class II antigens occurred in much higher frequency in patients with EM. The frequency of HLA-DQw3 (77.4%) increased with high significance compared with normal Caucasian control individuals (41.2%). An even stronger DQw3 association was found in the patient group with postherpetic EM (88.8%; relative risk, 9.41). Interestingly, all patients suffering from frequently recurrent EM were found to have the DQw3 allele (relative risk 44.2). The previously reported association to HLA-B15 was also seen and may be due to a linkage disequilibrium with the HLA-DR4 allele (66.6% in recurrent EM). Our data provide further evidence that classic recurrent EM is related to herpes simplex virus infection and should be regarded as a distinct entity within the enigmatic EM syndrome. DQw3 may serve as a helpful marker for distinguishing this entity from other diseases with EM-like lesions.
Twenty-two murine monoclonal antibodies directed to distinct polymorphic epitopes on HLA class I or class II antigens have been isolated and characterized using a simple protocol for fusion and hybridoma selection. Thirteen MAbs directed to class I antigens are reported here for the first time. The majority of these MAbs reacted with multiple specificities, often revealing a surprising sharing of epitopes. MAbs directed against single classically defined alloantigenic specificities were also obtained.
Monoclonal antibodies (Mabs) defining 14 distinct polymorphic epitopes have been produced against the class II antigens of HLA-DR3Dw3DQw2 cells. Population analysis indicates that Mab C1 is directed against the DQw2 specificity and Mab M6 against the DRw52 specificity. The remaining Mabs define epitopes shared by the class II molecules of DR3 and various other specificities. Seven DR3Dw3DQw2 haplotypes were examined and could be divided into two types based on the presence of the epitope defined by Mab M3. Analysis of DR2 and DR4 homozygous cells with these Mabs revealed several distinct patterns of epitope expression. These subdivisions were found to correlate with the cellularly defined Dw specificities.
Three monoclonal antibodies (MoAbs) directed against polymorphic epitopes of Ia antigens were used as tools for a serological and biochemical dissection of the class II products encoded by the HLA-DRw6 haplotype. MoAb 16.23 defines an epitope common to DRw13 and DR3 haplotypes, MoAb S5 defines an epitope common to DRw13 and DR2 haplotypes, and MoAb S2 defines an epitope apparently restricted to DRw13. Not all DRw13 cells express these epitopes. Analysis of 16 DRw6 homozygous typing cells showed that expression of all three epitopes was restricted to those DRw13 cells that carried the Dw18 antigen, the DRw13 Dw19 cells being negative. The relationships among the molecules bearing these epitopes were investigated using sequential immunoprecipitation in lymphoblastoid cell lines derived from genetically characterized individuals. In both DRw13 and DR2 bearing cells, the DR2 + w13 epitope was localized to a population of DQ molecules which also carried the DQw1 specificity defined by MoAb Genox 3.53. The S5 epitope is therefore a private specificity that distinguishes the DQw1 antigens encoded by the DR2 and DRw13 haplotypes from the DQw1 antigens encoded by other haplotypes. The DRw13 and the DR3 + w13 epitopes were both shown to be expressed on DR molecules that also carried a DRw52-like specificity. In a DRw13 haplotype encoding both the S2 and 16.23 epitopes, the epitopes appeared to be located on separate molecules. The antibodies described here can distinguish between DRw13 cells which carry different Dw antigens, identify a private specificity on the DQw1 antigen, and define two distinct DR molecules encoded by some DRw13 haplotypes.
The class III gene markers, C4A, C4B, C2 and BF were determined in 26 HLA genotyped families. In 6 of these families the inheritance of the C4A electrophoretic phenotype, C4A 3, A 2 could not be explained assuming the genetic model that the C4A component is controlled by only one locus (C4A) and suggests that both C4A 3 and C4A 2 are encoded by the same chromosome. This apparently duplicated C4A locus haplotype is common in Northern Europeans occurring at a frequency of at least 6%. In 4 families the C4A 3, A 2 'variant' occurred together with HLA-Bw35 and in 2 together with HLA-Bw55. Furthermore, it was striking that in each family the C4A 3, A 2 'variant' was found exclusively with the complotype FC3/20 which encodes no phenotypically expressed C4B locus product.