Search

The immunogenicity of human insulin (Novo, Monotard, Actrapid) or pork monocomponent (MC) insulin (Monotard, Actrapid) was studied in 102 HLA-DR-typed patients with newly diagnosed insulin-dependent diabetes mellitus (type I diabetes). After 6 mo of treatment, IgG-insulin antibodies were found in only 14% of the patients receiving homologous MC insulins, but in 29% of the patients on heterologous MC insulins. IgG-insulin antibody titers were significantly lower in patients treated with human insulin compared with diabetic patients who received the corresponding pork MC insulin preparations from the onset of their disease. The previously reported strong influence of immunogenetic factors in determining the magnitude of the anti-insulin immune response was supported by the findings obtained in the pork MC insulin-treated diabetic individuals. Incidence of circulating immune complexes was 14% and 5% after 3 and 6 mo, respectively, of treatment with human insulin, which is considerably lower than previously reported in patients using heterologous non-monocomponent insulin preparations.

As in the previous Workshops, the definition of Cw5 and Cw8 was rather difficult because of the cross-reactivity between Cw5 and Cw8 and because of the strong linkage disequilibrium between Cw5 and B44 as well as between Cw5 and B14.

Histocompatibility antigens play a certain role in the development of testicular tumours. 151 patients with testicular cancer (86 non-seminomatous germ cell tumours--NSGCT--and 65 pure seminoma) were typed for the HLA-antigens of the A, B, C and DR locus. 24 patients of the pure seminoma group and 50 patients of the NSGCT group had an elevated serum HCG level preoperatively. The antigen DR-5 was elevated in the seminoma group whereas the incidence of B-13 was increased in the NSGCT group. In terms of antigen distribution HCG-positive seminoma resembles seminomatous tumours rather than NSGCT.

HL-A antigens were determined in 18 unrelated patients with Gilbert's syndrome and 3 families where this condition occurred in 2 generations. The data obtained do not point out an association between HL-A antigens and Gilbert's syndrome.

In order to investigate the influence of pretransplant blood transfusions on renal graft survival, the results in 43 recipients with 10 or more transfusion (group A) were compared with those in 48 recipients with less than 10 or no transfusions (group B). In both groups cadaveric kidneys with mainly 3 or more mismatched histocompatibility antigens were transplanted. The incidence of preformed cytotoxic antibodies was similar in both groups (25.6% and 22.9%, respectively). The cumulative renal graft survival rate was significantly higher in the poly-transfused group: 85.6% +/- 6.1% and 73.4 +/- 7.9% after 1 and 2 years, respectively, in group A in comparison with 73.9 +/- 6.6% and 63.3 +/- 8.1% after 1 and 2 years respectively, in group B (Wilcoxon rank sum test: p less than 0.05). Severe renal rejection with a serum creatinine above 3 mg/100 ml was more frequently observed in group B than in group A. Enhancement due to blocking antibodies must be assumed as a possible explanation for the favourable effect of repeated pretransplant transfusions on graft survival rates.

Using a theoretical model formulas for the calculation of the chance of paternity exclusion for 2 closely linked autosomal loci with multiple allelism between which linkage disequilibrium exists are presented. With some examples their practicability for the HL-A system is shown.

The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8.

Eine reine Lymphocytensuspension wird mit einer moglichst reichhaltigen Auswahl von Antiseren gegen Leukocytenantigene (L—A und 4 Locus) zur Gewebetypisierung in Anwesenheit von Komplement inkubiert. Die AG-AK-Komplexe an der Zellmembran aktivieren Komplement, das an den antikorperbeladenen Lymphocyten cytotoxisch wirkt. So geschadigte Zellen nehmen den Farbstoff (z. B. Trypanblau, Eosin) auf und sind auch phasenoptisch von den nichtbetroffenen Zellen zu unterscheiden.

Die fundamentalen Arbeiten Medawars (1944, 1945) uber Hauttransplantationen bei Kaninchen bewiesen, das der Abstosung von Transplantaten ein immunologisches Geschehen, eine Antigen-Antikorper-Reaktion, zugrunde liegt. Die eminente praktische Bedeutung dieser Erkenntnis fuhrte zur intensiven Erforschung der daran beteiligten Antigene, die als Histokompatibilitats- oder Transplantationsantigene bezeichnet werden, und zur Entwicklung zahlreicher Methoden, um einem Organempfanger den am besten passenden Spender zuzuordnen. Durch einige dieser Techniken (Lit. bei Mayr, 1970a), wie z.B. den „Dritten Mann“-Test, den Lymphocyten-Transfertest, den Hamstertest und die gemischte Lymphocytenkultur, werden nicht die Antigene bei Empfanger und Spender, sondern nur deren Kompatibilitat bestimmt. Der direkte serologische Nachweis der Transplantationsantigene (Gewebstypisierung) kann aber auf relativ einfache Art durch den lymphocytotoxischen Test, die Komplementbindung an Thrombocyten oder die Leukoagglutination erfolgen.

Publisher Summary This chapter investigates the transient nature of anti-Gm. The intrauterine transfer of maternal Gm(+) gammaglobulin into a genetically determined Gm(−) foetus is the cause of the anti-Gm production of the child later on. The frequency of mother-child pairs (MCP) typical for this mechanism (TMCP) depends on the Gm distribution in the population. This chapter shows formulae and figures of Vienna. The hypothesis Gma + Gmax + Gmb = 1 is the basis of calculations presented in the chapter. As anti-Gm(b) and anti-Gm(f) were found to react practically identical, Gm(b) is not differentiated from Gm(f) in this study. All Gm(a,x) positive mothers with Gm(a,x) negative children are marked and the chance of anti-Gm production in these TMCP is calculated. The children can produce anti-Gm(a), anti-Gm(x), or anti-Gm(a) and anti-Gm(x). The chapter discusses all the experiments done in this study. Results obtained suggest possibility of immunization against Gm by blood transfusions and application of gammaglobulin. It is also indicated that an anti-Inv mechanism similar to the anti-Gm mechanism does not exist.

Another case of an HLA-B/HLA-C recombination is presented which shows that the locus HLA-C is situated between HLA-A and HLA-B.

A CHIMAERA can be defined as an organism whose cells derive from two or more zygotes1. In man, two categories of spontaneous and permanent chimaeras are recognised: blood chimaeras which arise from the exchange of blood-forming cells between dizygotic twins, and dispermic chimaeras which are the result of the fusion of two zygotes and of their growth into one body (for review see ref. 2). Blood chimaeras are usually identified because of blood-grouping problems caused by the mixture of different erythrocyte populations, while dispermic chimaeras who often present sex abnormalities are mainly detected by cytogenetic studies, although they also carry a mixture of different blood cell populations. In contrast to these typical cases, we now report a unique human chimaera who shows no mixture of blood cells as far as the genetic markers investigated are concerned, and who is only detectable by the investigation of the blood of her progeny (family Eiw., Fig. 1).

Diabetic children seem to be at risk to develop thyroid autoimmune disease. 110 diabetic children (48 fem, 62 males, mean age 12,3±3,8yrs.) were HLA-DRtyped and their sera were tested for the occurence of thyroid autoantibodies (TAB:antithyroglobulinantibodies and microsomal antibodies). Thyroid function was determined by measurement of thyroxine (T4) and thyrotropin (TSH) levels. The control group (n=50) was age- and sex matched. TAB were found in 18% of the diabetic children and in 6% of control (p 0,05). There was a predominance of females in the TAB positive group (m:f = 1:1,8). 60% of the TAB-positive diabetic children were positive for HLA-DR3 compared to 54% of the TAB-negative diabetic children. Only one diabetic child had mild hypothyroidism. We conclude that HLA-DR3 does not represent an additional risk factor for the development of thyroid autoimmune disease and thyroid dysfunction is a rare phenomenon in diabetic children.