Brief summary of Ninth International Histocompatibility Workshop.
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Biomedical subjects
Publications and source records attributed to E Albert.
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Twelve families with a sibling pair affected by seronegative juvenile chronic arthritis (JCA) were studied. The ratio of HLA haplotype sharing was significantly different from that expected. No common haplotype was found. All 10 sibling pairs concordant for pauciarticular disease shared 2 haplotypes and the other 2 pairs shared one haplotype. These findings are evidence of a genetic predisposition to develop pauciarticular onset JCA in the families studied and suggest the presence of a disease susceptibility gene or genes within the major histocompatability complex.
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Tissue typing (HLA-A, -B and -DR) was carried out on 92 patients with coeliac disease (CD) and on a further 71 first degree relatives of 13 of these patients. Results of antigen frequencies in unrelated patients and segregation analysis in families shows that HLA-DR3 but not HLA-DR7 is positively associated with CD. Haplotype and sib-pair data from these coeliac families suggest that with all of them, genetic susceptibility to CD lies in the HLA region of the sixth chromosome. In families where the coeliac proband has HLA-DR3, the relative risk to siblings who also have this antigen is increased 35 times.
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The clinical course of children with IgM rheumatoid-factor-positive chronic arthritis closely resembles that of seropositive rheumatoid disease in adults. The frequency of HLA DR4 is known to be increased in adults with seropositive rheumatoid arthritis, but the first major report on childhood arthritis did not suggest a correlation, though only 8 seropositive cases were included. Fifty-two children with polyarthritis beginning before the age of 16 who persistently carried IgM rheumatoid factor were studied. HLA DR4 was present in 60% of these children but was found in only 29% of 93 patients with seronegative juvenile arthritis and 27% of a normal adult population. These results suggest immunogenetic similarities in patients with seropositive arthritis irrespective of age of onset.
Thorough reexamination of 70 patients in a long-term psychiatric ward led to partial revision of the diagnoses. Classified on the basis of Leohards's differential diagnostics, the large proportion of schizophrenics has dropped by over a third from 78% to 47%. Half of the 22 psychosis originally considered to be schizophrenia proved to be curable phasic and cycloid psychoses which had previously been overlooked and the other half were mental disturbances caused by brain-organic damage. A third of the chronic mental illnesses were found to be rooted in somatic brain lesions.
A grinding machine for preparing thin nondecalcified bone sections after methacrylate embedding is described. A second micrometer screw with diamond is mounted in a specimen holder to adjust exactly the final thickness of the sections. The bone specimens are ground by a turnably mounted rough glass plate. The desired thickness of the sections is reached as soon as the diamond tip of the micrometer screw touches the glass surface. The sections can are used for microradiography, fluorescence microscopy, and histochemical investigations.
The influence of antigens of the major histocompatibility complex (MHC) on the production of interferon (IFN) alpha or IFN gamma by human peripheral blood leucocytes (PBL) in vitro has been studied. Synthesis of IFN gamma by PBL stimulated with purified phytohaemagglutinin (PHA-P) or protein A of Staphylococcus aureus (SpA) appeared not to be controlled by MHC antigens. The production of IFN alpha, however, was influenced by the HLA type of the donor. Low responsiveness of PBL to inducers of IFN alpha (influenza virus, Molt 4 cells) was associated with HLA-DR 2. Implications of these observations for studies of IFN production and natural killer (NK) cell activity are discussed.
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Three patients from two families with complete hereditary deficiency of the fourth component of complement (C4) and systemic lupus erythematosus are described. The syndrome presented by these patients is characterized by early onset in life; exquisite sensitivity to sunlight and to cold exposure, the latter resulting Raynaud's phenomenon; and skin lesions involving not only exposed areas of the body but also palms and soles and presenting as butterfly rashes, maculopapular eruptions, and lesions similar to those of chronic discoid lupus erythematosus, with marked scaling, atrophy, and scarring. Lupus erythematosus (LE) cell tests were negative and antinuclear antibody (ANA) titers low or negative. The male patient of our series died at the age of 31/2 years from septicemia, whereas the two girls, aged 18 and 11 years, respectively, were alive at the time of writing. The C4-deficient gene is associated with HLA-Aw32, Bw38, and Bf S in one family and with HLA-A30, B18, DR7, and Bf S1 in the other family; the latter is the second family in which this HLA haplotype has been found to be associated with hereditary C4 deficiency.
A 13-year-old boy suffering from celiac disease (CD) developed shortness of breath at exercise and episodes of malaise, fever and acute dyspnea following contact with pigeons. Lung function testing and chest X-ray suggested interstitial lung disease. Serum precipitins and a combined systemic and pulmonary reaction 4 h after challenge with an extract of pigeon droppings confirmed bird-fancier's lung. This case exhibits two points of interest. Extrinsic allergic alveolitis was found in childhood in combination with CD and it may be considered that both these diseases are based on one common immunologic disorder; HLA-typing of the boy's family showed that he carried HLA-DR 3 in a double dose and was therefore homozygous for HLA-DR 3. This is of some interest because extrinsic allergic alveolitis and CD are both associated with HLA-DR 3.
In March, 1981, a 37-year old patient underwent cardiac transplantation, the first to be performed in Germany since 1969. Subsequent to the successful procedure, the patient has now been followed for more than 19 months. The indication for the intervention was established on the basis of endstage coronary artery disease. The operation was performed according to the technique of Lower and Shumway. Immunosuppression, in the early postoperative phase, was carried out with antithymocyte globulin, azathioprine and corticosteroids with administration oriented on the T-lymphocyte and total leukocyte counts as well as analysis of myocardial biopsies. In the late postoperative course, dosage of immunosuppressive agents was based almost exclusively on biopsy findings. Within the course of immunosuppressive therapy for cardiac transplantation, in particular, initial experience was gained with the use of antithymocyte globulin which was given in dosages of up to 12 mg/kg daily. The antithymocyte globulin proved effective for more than six weeks postoperatively. The alterations in immunosuppressive treatment necessitated by two gastrointestinal complications (perforated gastric ulcer, perforation of the small intestine) enabled a comparative analysis of the results of therapy with cyclosporin A given orally, intravascularly and intravenously. The Patient continues to be maintained on a regimen of cyclosporin A and corticosteroids and his general condition is good. For future cardiac transplantations, in the early postoperative course, alternating treatment with antithymocyte globulin, azathioprine and corticosteroids, on the one hand, with cyclosporin A and corticosteroids, on the other hand, would seem meaningful both to minimize adverse reactions as well as to provide effective immunosuppression. The experience rendered would promise to facilitate management of patients after cardiac transplantation.
The association between HLA and coeliac disease (CD) was studied in the Jewish population of Israel. A total of 112 patients were typed for HLA-A,B,C antigens, including 67 patients whose families were typed in order to deduce the genotypes. Forty-seven patients were typed for HLA-DR antigens. The HLA-A,B,C data show a pattern of association, which is similar to that found in European CD patients: HLA-B8 is increased, although to a lower degree; a suggestive, insignificant increase for Aw30, B13 and Cw6 and a decrease of Bw35 were noted. The DR antigens DR3 and DR7 are associated with CD in the Jewish population. An excess of DR3/DR7 heterozygotes was noted. The data from family and population studies support a model in which two different HLA-DR associated genes are interacting.
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In the last four years 125 renal transplantations were performed at the Transplantation Center in Munich. The mortality rate after transplantation could be lowered to below 10% in the first year; on the other hand the rate of loss of transplants observed in the Center was 40% in the same period. After mentioning the individual surgical complications following renal transplantation with reference to our own patients. The effect of blood transfusions on the survival time of the transplant is dealt with. It was found that transplant survival rate increased with the rise in the number of blood transfusions before the transplantation.
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