W.R. Mayr

COXSACKIE-B-VIRUS-SPECIFIC IgM RESPONSES, COMPLEMENT-FIXING ISLET-CELL ANTIBODIES, HLA DR ANTIGENS, AND C-PEPTIDE SECRETION IN INSULIN-DEPENDENT DIABETES MELLITUS

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.

The Relation of Parental Sex and Age to Recombination in the HL-A System

Data on the effect of parental sex and age on recombination between the LA and FOUR loci are pre sented for 62 families. Maternal recombination is 50% more frequent than paternal. No effect of parental age on recombination was demonstrated.

HAEMOLYTIC TRANSFUSION REACTIONS DUE TO HLA ANTIBODIES: A Prospective Study Combining Red-cell Serology with Investigations of Chromium-51-labelled Red-cell Kinetics

In a prospective study to see whether HLA sensitisation is associated with increased red-blood-cell (RBC) destruction after HLA-incompatible transfusion, chromium-51-labelled RBC survival and site of sequestration were monitored in nine patients in whom HLA antibodies had developed after RBC transfusions. The donors selected were compatible in ABO and RBC-specific antigen systems but mismatched for the HLA antigen in question. Haemolytic transfusion reactions occurred in all four patients who received HLA-B7-incompatible RBC. A direct radioimmune anti-IgG test became positive, Cr51-RBC survival was very short (22.3, 36.9, 41.4, and 44.0 days), and excess sequestration in the spleen was measured. There was a rise in serum lactic dehydrogenase and a fall in haptoglobin. HLA-B7 antibody was detected in the eluate prepared from RBC collected after transfusion. A similar reaction was found in only one further patient, caused by an HLA-A2 incompatibility. No indications of immune-mediated RBC sequestration were discernible after transfusion of HLA-B7-compatible RBC in one of the patients who had shown a reaction with HLA-B7-incompatible blood, nor in any of the other patients who received HLA-B7-compatible RBC. The haemolytic transfusion reactions could not be anticipated by conventional crossmatch procedures, nor by the measurement of the Cr51-RBC survival 1 h after transfusion.

FAMILIAL ISLET-CELL ADENOMATOSIS

Familial multiple adenoma of pancreatic beta-cells is described for the first time. The occurrence of diabetes mellitus in different members of the family raises the possibility of a common genetic origin for the multiple islet-cell adenomas and the diabetic trait. The evidence suggests that this gene is autosomal and dominant, that it is not linked with the HLA antigens, and that is causes an abnormal sensitivity of the beta-cells, which become hyperplastic or hypofunctional.

Antibody-dependent killer-cell function in insulin-dependent diabetes mellitus

Antibody-dependent killer-cell activity (ADCC) was determined in 36 insulin-dependent diabetics (IDD) and 32 controls. The medians of cytotoxic indices obtained by using either antibody coated chicken red blood or Helacells as targets were statistically significantly reduced in the diabetics (p< 0.05 for both systems). However, due to the wide range and considerable overlap of the cytotoxic indices observed in patients and controls, the biological significance of these mathematical differences remains to be determined. The duration of the disease did not have any influence on killer (K) cell function and only a slight tendency for decreased ADCC during episodes of poor metabolic control was noted/Further analysis of the influence of diabetes-associated factors did not reveal any definite correlation between the functional K cell deficit, the insulin dosage administered, the insulin antibody titers, the blood glucose at the time of sampling, the 24 hour glucosuria and IDD-associated immunogenetic factors.

Patients with Aplastic Anemia Frequently are Histocompatible (HLA-DR, MLC) with Their Mothers

The real cause of Aplastic Anemia (AA) still is unknown. Some imbalances in the distribution of the HLA-antigens, however, have been reported in families of AA patients (1) (2), but none of them definitely could be confirmed.

Genotypisierung von HPA-1 bis HPA-5 mit der allelspezifischen Ligasekettenreaktion nach Amplifikation von genomischer DNA in einer Multiplex-PCR

Platelet-specific antibodies are involved in refractoriness to platelet transfusions, neonatal alloimmune thrombocytopenia, and posttransfusion purpura. Binding to different epitopes on platelet glycoproteins, human platelet antigens (HPA), they can cause severe thrombocytopenia. The polymorphic DNA regions of the best known HPA systems HPA-1 to HPA-5 were amplified from genomic DNA in a multiplex polymerase chain reaction (PCR). An automatable ligation-based assay (LCR) using allele-specific oligonucleotide probes was developed for rapid genotyping. The results were correlated with the well established allele-specific restriction enzyme assay (ASRA), and the phenotype was determined by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA). We found a 100% concordance of genotypes between the HPA-LCR in 54 cases of NAIT, PTP and normal controls with the established methods. The gene frequencies calculated from 216 German and 55 Japanese random blood donors were similar to those determined by other time-consuming typing methods in a Caucasian and Japanese population, respectively. Multiplex PCR and the allele-specific HPA ligation assay provide a reliable tool for typing both small series and all platelet donors of a transfusion center in order to identify rare genotypes necessary for the treatment of patients suffering from NAIT, PTP or refractoriness to platelet transfusions.

Thrombozytentransfusion: Plättchenanstieg in Abhängigkeit von klinischen und immunologischen Voraussetzungen

Bei 35 Patienten mit schwerer transfusionsbedurftiger Thrombozytopenie (AML n = 10; ALL n = 4; CML n = 1; idiopathische Myelofibrose n = 1; aplastische Anamie n = 1; aplastische Phase nach Knochenmark

RISK FACTORS IN TESTICULAR CANCER

Risk Factors for Testicular Cancer A risk factor is anything that changes your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking and diet, can be changed. Others, like a person’s age or family history, can’t be changed. But having a risk factor, or even many, does not mean that you will get the disease. Just as not having risk factors doesn’t mean you won’t get the disease. And some people who get the disease may not have had any known risk factors. Even if a person with