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After a short listing of the human blood groups, the genetics of the markers in human blood and the mapping of several blood group loci on the chromosomes are discussed.

After a survey of the genetics of the HLA system, the possibility to type bloodstains for HLA gene products is discussed.

Fifty-four thyrotoxic patients (23 with and 31 without endocrine ophthalmopathy EOP) were HLA typed for A, B, and C locus antigens. The frequency of this third locus antigen CW3 was found to be significantly increased in patients with EOP compared with those thyrotoxic patients without EOP. These findings point to a possible genetic heterogeneity in thyrotoxic patients with or without EOP. HLA B8 was observed in only 10 of the 54 patients studied, which is not in accordance with the previously reported statistically significant increased frequency of this B locus antigen in thyrotoxic patients.

Immunization of a mother negative for the platelet-specific antigen P1A1 against the P1A1 antigen of her child induced neonatal alloimmune thrombocytopenia. This prompt immune response occurred in her first pregnancy and we were therefore interested to study whether there is an association with genes located within the major histocompatibility complex. We deduced haplotypes of HLA-A, B, C and DR as well as of complement C2, C4 and Bf in the maternal family members.

Left side orthotopic homotransplantation of the lung was performed in 8 mongrel dogs pre-sensitized by full-thickness skin transplants. The degree of sensitization was assessed by control of the lymphocytotoxic antibody titre. The behaviour of haemolytic complement activity, as well as the alterations in antibody titre were recorded up to 60 minutes after opening of the anastomoses. Evaluation was performed by analyses of significance. A significant decrease in lymphocytotoxic antibody titre (p less than 0.001), as well as a significant diminution in complement activity (p less than 0.01) was observed in blood samples from the pulmonary vein of the graft during the first five minutes following recirculation. This resulted from an interaction of both systems in the immune reaction. The further complement consumption by the graft in contrast to the constancy of the lymphocytotoxic antibody titre in the subsequent post-transplantation period can be explained by antibody-independent complement activation. Vena cava-- pulmonary vein differences in the lymphocytotoxic antibody titre and complement activity are correlated only five minutes after opening of the anastomoses (r = 0.75), which confirms the independence of both systems during later course of the reaction.

Within a sample of 6107 non related subjects no dependency of the Gm-types from the Rh-phenotypes could be observed. These data as well as the results of linkage studies do not suggest the localisation of the Gm-loci on chromosome 1.

Levels of platelet-associated immunoglobulins (PAIg) IgG, IgM, IgA and complement C3c were related to parameters of 111Indium-labelled platelet kinetics in 17 patients with chronic idiopathic autoimmune thrombocytopenia (cAITP). Elevated levels of PAIg/C3c were found in 14 patients (82%) (PAIgG n = 13, PAIgM n = 11, PAIgA n = 1, PAC3c n = 5). Only PAIgG correlated with platelet counts (RS = -0.71, p less than 0.01). Mean platelet life span (MLS) was shortened in all patients (median 12.0 h, range 0.3-45.6 h) and correlated with the platelet counts (RS = 0.49, p less than 0.05). MLS was correlated with PAIgG (RS = -0.52, p less than 0.05), but not with PAIgM, PAIgA, or PAC3c. The site of sequestration was splenic in 10 patients and splenic-hepatic in 7 patients. Although no significant correlation between either site of platelet sequestration and any of the investigated PAIg/C3c was demonstrable, platelets coated with higher PAIgG levels were more readily sequestrated in the spleen, while elevations of PAC3c were found in 4 out of 7 patients with hepatic involvement.

In 41 patients with open-angle glaucoma and 450 healthy, unrelated controls of identical ethnic origin the frequencies of 36 HLA antigens were determined using the microlymphocytotoxicity test. In contrast to recent publications it was not possible to confirm a significant difference in the incidence of the antigens in both groups. The possible reasons for this difference are discussed.

One hundred fifty patients with toxic and scintigraphically diffuse goiter were HLA typed (A, B, C, DR). One group consisted of 101 patients with concomitant Graves' ophthalmopathy and/or TSH-binding inhibiting antibodies (TBIAb). Forty nine patients had neither ophthalmopathy nor TBIAb. The former group showed a higher prevalence of HLA-B8 and DR3 compared to a normal control group. The latter group showed a higher frequency of HLA-DR5, whereas the HLA-B8 and DR3 antigens were slightly below normal prevalence. These data indicate an immunogenetic heterogeneity in patients with toxic diffuse goiter. A group of 47 hyperthyroid patients with single autonomous thyroid adenoma had no increased prevalence of any HLA-antigens. Patients with long term remission did not show an altered prevalence of any of the HLA antigens compared to controls. In contrast, patients with Graves' ophthalmopathy and/or TBIAb activity who relapsed had a significantly higher prevalence of HLA-B8 DR3, whereas patients without TBIAb and eye signs who relapsed had a significantly higher prevalence of HLA-DR5 than the control group.

To evaluate the role of Coxsackie B viruses in the pathogenesis of insulin-dependent (juvenile-onset, type 1) diabetes mellitus (IDDM), attempts were made to correlate virus-specific IgM responses with HLA genes, autoimmune responses, and C-peptide secretion. HLA DR3, DR4, or both were present in 73 of 90 (81%) diabetic patients; 22 of 23 (96%) with Coxsackie-B-virus-specific IgM had at least one of these HLA types, compared with 51 of 67 (76%) without virus-specific IgM. There was no correlation between HLA A, B, or C types or immunoglobulin allotypes and virus-specific IgM responses. 16 of 22 (64%) patients with Coxsackie-B-virus-specific IgM compared with 26 of 72 (36%) without had complement-fixing islet-cell antibodies; no relation was found between virus-specific IgM and antibodies against thyroid or adrenal tissue or parietal cells. C-peptide secretion was significantly lower in patients with Coxsackie-B-virus-specific IgM.

By isoelectric focusing in a pH range of pH 3.5-9.5 or of pH 5-8, and by using a functional or an immunological detection, a genetic polymorphism of plasminogen can be demonstrated. In Caucasoids, 2 common alleles--PLGA (frequency 0.67) and PLGB (frequency 0.30)--as well as several rare variants (sum of their frequencies 0.03) exist. Systematic studies on the functional activity of the various plasminogen gene products should be performed in order to analyse whether or not a difference of plasminogen activity can be observed amongst the possible phenotypes and in order to see whether or not the various plasminogen phenotypes have any clinical significance.

A panel of 120 HLA-A, -B, -C and -DR typed Austrians has been typed for HLA-D by the use of 26 Homozygous Typing Cells (HTC). The new Austrian HTC, partly defined by the 9th International Histocompatibility Workshop (9WS), partly by a checkerboard experiment with internationally well defined reference HTC, type for HLA-Dw1 to -Dw7 and an obviously new, so far unknown HLA-DR2 related HLA-D determinant. Associations of HLA-DR and HLA-D antigens in Austria and their frequencies are determined. Antigen frequencies in Austria are compared to frequencies in other Caucasoid populations.

The role of genetic factors in humoral anti-insulin-response was studied in 87 patients with juvenile onset diabetes. A significant insulin antibody formation was found in 76 (87%) juvenile diabetics. By dividing these patients in four groups according to different heights of insulin antibody levels (non-, low-, moderate- and high-responders) a positive or negative correlation between humoral anti-insulin response and certain HLA antigens could be found. Non-responders showed a close association with HLA-B7 positivity, whereas in the insulin high-responder patients, a considerable decrease of HLA-B8 and increase of HLA-Bw15 and HLA-Cw3 was found. These findings indicate that certain genetic constellations within the HLA complex might have an important part in determining humoral anti-insulin immunity.

A close correlation between juvenile mellitus and HLA-B8, HLA-BW15 and HLA-CW3 was found. Association of these antigens with juvenile diabetes mellitus was closely dependent on the ages of onset of the disease. Frequencies of BW15 and CW3 showed a remarkably low incidence in the childhood diabetics (0-15 years old) and were found increased in the patients with later (16 years or older) onset diabetes. HLA-B8 frequencies were found increased in all the groups of diabetics with different ages of onset. These findings point to the importance of HLA-B8 in childhood and HLA-B8, BW15 and CW3 in the later onset juvenile onset diabetes mellitus (JOD).

We describe a 46-year-old white woman with typical clinical features of posttransfusion purpura (PTP) whose serum held a platelet-specific alloantibody reactive with an antigen antithetical to Baka, i.e. anti-Bakb. The specificity of the antibody was confirmed by family analysis, a population study (expected versus observed gene frequency: 0.3651 versus 0.3984; n = 105) and localization of the antigen on glycoprotein IIb in radioimmunoprecipitation. Typing of family members and blood donors for platelet antigens disclosed that the patient had been preimmunized by two blood transfusions in 1981, while fetomaternal incompatibility for Bakb was ruled out (her three children and their father were Bakb negative). Treatment of PTP with corticosteroids and platelet transfusions was ineffective, but infusion of high-dose intravenous IgG resulted in a rapid increase in the platelet count.

One hundred twenty-seven white European patients with differentiated thyroid cancer were typed for human lymphocyte antigen (HLA) DR specificities. There was no significant deviation from the HLA-DR distribution observed in 160 normal patient controls, neither in the entire group nor in the patient groups with nonmedullary types of thyroid cancer (61 with papillary and 44 with follicular, all nonradiation associated). Also, subdivision of patients with nonmedullary thyroid cancer according to age at diagnosis, presence of metastases, and presence of thyroglobulin antibodies in serum showed no significant deviation from the HLA-DR distribution. For the patients with medullary thyroid cancer (only sporadic [n = 20] or inherited isolated [n = 2] forms, no multiple endocrine neoplasias), there was a significant increase of HLA-DR2 (11 of 22 cases [50%]) in comparison with control patients (22%; P corrected to 0.02; relative risk, 3.6). These data suggest, in contrast to previous reports, that there is no genetic influence on the development of nonmedullary types of differentiated thyroid cancer. Medullary thyroid cancer without multiple endocrine neoplasia, however, may be associated with HLA-DR2.

The algorithm computes gene- and haplotype frequencies from phenotype data of the HLA system. It is an iterative procedure which finds these frequencies by employing statistical and combinatorial considerations. The probabilities for homozygosity of single genes are used as essential parameters. They are simultaneously computed by the algorithm. These parameters are mainly needed for the evaluation of alleles, whose gene product cannot be determined serologically.

The importance of the HL-A system for blood transfusions (febrile reactions, substitution of leukocytes and platelets, prevention of anti-HL-A immunisation) is described. Furthermore, the problem of finding an HL-A identical donor for a given recipient which arises from the polymorphism of the HL-A system is discussed.

Phenotype and gene frequencies of the GLO I polymorphism in Vienna are given. No exception to the postulated rule of inheritance could be found in 23 families with 51 children and 132 mother-child pairs. Linkage with the HLA system is confirmed, but no linkage disequilibrium between GLO alleles and HLA-A, B, C genes was detected. The use of the GLO I polymorphism in paternity cases is discussed.

Concanavalin A-induced suppressor cell activity was found moderately but significantly (P less than 0.05) decreased in RA patients treated with nonsteroidal antiinflammatory drugs (31 +/- 7% suppression) as compared to patients on remission-inducing drugs, such as gold, penicillamine, or chloroquine (51 +/- 6%) or to healthy individuals (50 +/- 6%). Also, lymphocytes from patients with antibodies to collagen mediated lower suppression (33 +/- 7%) than lymphocytes from patients without evidence for these autoantibodies (61 +/- 11%). No significant difference between patients and controls or between individual groups of patients were observed in regard to IgM and IgG secretion induced by pokeweed mitogen. Thus, although no indication for a severe derangement of regulatory cells in peripheral blood of RA patients could be observed in this study, a slight deficiency of ConA-inducible suppressor cells that may be reverted by remission-inducing drugs seems to be present in RA.

In patients with Graves' hyperthyroidism, the relapse rate after antithyroid drug treatment is in the range of about 30-70%. Different attempts have been made to obtain criteria for the prediction of the clinical outcome after drug therapy, especially HLA-DR typing and measurement of TSH receptor antibodies. So far, very conflicting results have been reported. This is not surprising in view of the many genetically controlled and environmental factors that play a role in the pathogenesis of this disease. Moreover, most reports are based on retrospective studies with a relatively small number of patients. Our own data, obtained in a prospective multicenter study, yield strong evidence against the relevance of HLA-DR3 typing (n = 187, sensitivity = 0.38, specificity = 0.67) or measurement of TSH receptor antibodies at the end of therapy (n = 269, sensitivity = 0.49, specificity = 0.72) for the prediction of the clinical course after drug treatment.

The intensive supportive haemotherapy which has to be used in bone marrow transplantation is discussed, taking mainly into account platelet transfusions. Ways to avoid alloimmunizations against platelet antigens, especially HLA-ABC antigens, are shown (use of HLA-AB homozygous donors or of cross-reacting groups).

In the search for markers either closely linked to or identical with the hypothetical "diabetogenic major histocompatibility gene," immune region-associated alloantigens were defined in 80 patients with insulin-dependent diabetes and in 107 controls. A close association between the Ia-type alloantigen DRw3 and DRw4 and insulin-dependent diabetes was obtained. DRw3 was found in 36% and DRw4 in 32% of the patients compared to 11% and 16%, respectively, of the controls. In addition, a significant influence of DRw3 and humoral anti-islet-cell autoimmunity could be observed, which was found to be due to a high incidence of DRw3 in those patients with islet cell antibody persistence. Islet-cell antibodies (ICA) were observed in 60% of the DRw3-positive patients compared to only 9% of the DRw3-negatives with longstanding disease (greater than 5 yr). These data show a significant association between insulin-dependent diabetes and the Ia-type alloantigens DRw3 (p uncorr. less than 0.0005) and DRw4 (p uncorr. less than 0.025). Furthermore, they provide direct evidence of an association between an Ia-type alloantigen and persisting humoral autoimmune responsiveness in man.

The frequency of 36 HLA-SD antigens were investigated in 42 patients with cervix cancer, 36 female patients with recurrent Herpes genitalis and 450 healthy controls. The only significant difference between the 3 groups was an increase in the frequency of BW 15 in the cervix cancer patients. The patients with recurrent Herpes genitalis--who were sero-epidemiologically determined to have a higher risk of developing a cervix carcinoma-showed no significant difference in their HLA-SD antigen frequencies in comparison with the controls and the cervix carcinoma patients.

A method appropriate for identification and quantification of circulating antibodies reacting with donorlungantigens is presented in allogenous lungtransplantation. Following incubation of native tissue-slides taken from the second removed but not grafted donor lung with the recipient's serum, the specific humoral antibodies are detected by indirect immunfluorescence. Quantifying evaluation is performed by serum-dilutions. The preexisting specific antibody-titer found in DLA-sensitized animals shows a significant correlation with the duration of graft function when compared with lymphocytotoxic antibody-titer. In unsensitized dogs a regular appearance of circulating specific antibodies can be seen beginning from the fourth or fifth postoperative day. The increasing antibody-titer during further course is a feature of a humoral graft rejection represented in the periphereal blood-circulation.

Humoral immunity to bacterial antigens was tested in 49 tissue typed patients with juvenile onset diabetes mellitus (JOD) and in 50 healthy controls. The number of patients with agglutinins to E. coli and staphylococci was significantly lower compared to controls (p less than 0.001, p less than 0.01 respectively). Missing antibody formation to pertussis and diphtheria toxoid could also be detected in a higher percentage of JOD patients than of controls (p less than 0.05; p congruent to 0.05, respectively). By contrast heteroagglutinins to sheep and rabbit erythrocytes were found in similar proportion in both groups and the values of immunoglobulin serum concentrations showed no difference between patients and controls. In addition no correlation between antibody formation and genes of the HLA complex was found. It is suggested that the severely reduced agglutinin formation to bacteria antigens might be partly responsible for susceptibility to bacterial infections in juvenile diabetics.

The interrelationship between Coxsackie B4 (CB4) virus antibodies, islet-cell antibodies and HLA B8 was studied in 67 patients with juvenile-onset diabetes mellitus (JOD). In 41 JOD patients (61%) CB4 antibodies (greater than 1:4) were found. A high prevalence (69%) of significant CB4 antibody titers (greater than 1:64) was observed in patients with age at onset between 11 and 20 years compared with those with age at onset below or over that age-range (27% and 33%, respectively). Islet-cell antibodies (ICA) could be detected only in 11 JOD patients, which is probably due to the relatively long mean duration of disease. However, 8 of them presented with significant CB4 antibody production. Although no correlation between CB4 antibodies and the JOD-associated HLA-antigens (B8, Bw15, Cw3 and B7) could be detected in the entire group of JOD patients, a close association between ICA persistence and HLA B8 was found. Furthermore, in the ICA-positive, moderate or high CB4 antibody titers were prevalent. Thus, the present data point to a possible interrelationship between CB4 virus antibodies, persistent ICA production and HLA B8 in a minor proportion of JOD patients. However, it seems premature to assume direct implication of these factors in the pathogenesis of JOD.

Classification of the hereditary motor and sensory neuropathies is discussed and findings reported in the recent literature are compared to our own findings in a kinship with autosomal dominant CMT. Previous studies in CMT-families with comparable slow nerve conduction velocities had shown positive linkage of this hereditary neuropathy to the Duffy blood group locus; however, blood group typing in the recently studied kinship excluded close linkage, which may indicate the existence of another sub-group in this entity. Testing of visually evoked potentials in this kindred demonstrated significant differences in P 100 latencies of the families of twin brothers. This intrafamilial difference may also be an expression of heterogeneity.

26 pig kidneys were perfused in a "Gambro" kidney perfusion machine. The perfusates used were unmodified canine plasma and serum, as well as complement-free plasma, gamma-globulin solutions obtained from dogs immunized against pig leucocytes (ALG) and 2-mercapto-ethanol treated ALG (2 ME-ALG). The typical pig-to-dog xenograft rejection was reproduced by ex vivo perfusion with native dog plasma and serum. Using complement-free dog plasma, ALG and 2 ME-ALG pig kidneys could be perfused for several hours without significant increase in perfusion resistance. 22 pig kidneys, pretreated by perfusion for 2 hours with complement-free dog plasma, ALG and 2 ME-ALG, were transplanted on to the vessels of the neck of recipient dogs. Grafts pretreated with decomplemented dog plasma and 2 ME-ALG were rejected in the usual fashion within 5 to 20 min. Pretreatment with ALG resulted in a prolongation of graft function for 80 to 100 min. It is suggested that ALG exerted a transient blocking effect on the cytotoxic action of recipient IgM resembling passive enhancement; this phenomenon may be limited to sites with low antigen density, corresponding to in vitro findings of passive enhancement on cells with low surface antigen density.