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At least 883 records · Page 49Linked to original sources
PubMed1996

Determinants of a normal (versus impaired) oral glucose tolerance after combined pancreas-kidney transplantation in IDDM patients.

After successful pancreas transplantation, insulin-dependent diabetic patients are characterized by a normal or at worst impaired oral glucose tolerance (World Health Organisation criteria). It is not known which pathophysiological mechanisms cause the difference between normal and impaired oral glucose tolerance. Therefore, we studied 41 patients after successful combined pancreas-kidney transplantation using stimulation in the fasting state with oral glucose (75 g), intravenous glucose (0.33 g/kg) and glucagon bolus injection (1 mg i.v.). Glucose (glucose oxidase), insulin and C-peptide (immunoassay) were measured. Repeated-measures analysis of variance and multiple regression analysis were used to analyse the results which showed: 28 patients had a normal, and 13 patients had an impaired oral glucose tolerance. Impaired oral glucose tolerance was associated with a greatly reduced early phase insulin secretory response (insulin p < 0.0001; C-peptide p = 0.037). Age (p = 0.65), body mass index (p = 0.94), immunosuppressive therapy (cyclosporin A p = 0.84; predniso(lo)ne p = 0.91; azathioprine p = 0.60) and additional clinical parameters were not different. Reduced insulin secretory responses in patients with impaired oral glucose tolerance were also found with intravenous glucose or glucagon stimulations. Exocrine secretion (alpha-amylase in 24-h urine collections) also demonstrated reduced pancreatic function in these patients (-46%; p = 0.04). Multiple regression analysis showed a significant correlation of 120-min glucose with ischaemia time (p = 0.003) and the number of HLA-DR mismatches (p = 0.026), but not with HLA-AB-mismatches (p = 0.084). In conclusion, the pathophysiological basis of impaired oral glucose tolerance after pancreas transplantation is a reduced insulin secretory capacity. Transplant damage is most likely caused by perioperative influences (ischaemia) and by the extent of rejection damage related, for example, to DR-mis-matches.

Adult↗
PubMed1986

Islet cell antibodies and the development of diabetes mellitus in relation to mumps infection and mumps vaccination.

Islet cell antibodies were investigated in 127 non-diabetic children after mumps infection and in four out of seven children who developed diabetes mellitus shortly after active mumps vaccination. Twenty-one of the children who had mumps and all four vaccinated children who were tested had islet cell cytoplasmic antibodies. In contrast, islet cell surface antibodies were detected in 43 out of 68 patients with mumps infection and in 32 out of 44 patients with other viral diseases. All but one mumps-infected child and all the other viral infected patients investigated did not develop diabetes mellitus. The mumps-infected ICA positive children did not show those HLA-frequencies associated with Type 1 diabetes.

Antibodies↗
PubMed1989

The DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci.

The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population, in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a DQw4 allelic product. This study characterizes the DR subregion of that haplotype. cDNA sequence analysis has revealed a DR beta gene which differs at several positions from previously described DR3 beta 1 genes. It is postulated that a gene-conversion-like event with a DRw52 beta gene as donor has generated some of these differences. The haplotype carries a DRw52a allele as defined by oligonucleotide hybridization studies. DNA restriction fragment analysis using a family and several unrelated individuals has allowed us to identify DR alpha and beta fragments associated with the DR3(w18),DQw4 haplotype. The most striking observation is that the DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci. Several genetic mechanisms including reciprocal recombination, gene conversion, and point mutation were involved in generating the differences between these haplotypes. Once established, the DR3(w18),DQw4 haplotype appears to be relatively stable in the population.

Amino Acid Sequence↗
PubMed1992

Cytotoxic flow-cytometric crossmatches (flow-tox): a comparison with conventional cytotoxicity crossmatch techniques.

Detection and avoidance of donor-reactive antibodies in the sera of potential organ transplant recipients is key to a successful transplant outcome. Techniques of antibody detection that use flow cytometry are more sensitive than those that rely upon a visual determination of cytotoxicity. However, as conventionally performed, flow-cytometric crossmatches do not distinguish between cytotoxic (complement fixing) and noncytotoxic antibodies because both types of antibodies can bind to a cell and be detected by laser-activated fluorochrome photon emission. In 1989 we described two techniques for detecting cytotoxic antibodies using flow-cytometric techniques [1]. In 1990, we expanded the application of these new techniques that we called flow cytotoxicity assays or "Flow-Tox" [2]. Flow-Tox crossmatches demonstrate an increase in both sensitivity and specificity over conventional cytotoxicity crossmatches.

Cell Separation↗
PubMed1994

Effect of panel reactive antibody on live related donor kidney transplantation: Indian experience.

Serum samples from 95 recipients, transplanted with kidneys from live related donors, were tested for the presence of panel reactive antibodies (PRA) in pre- and post-transplant serum samples by the extended microdroplet lymphocytotoxicity test. The immunoglobulin class of antibodies was tested by treatment of serum with dithiothreitol. A significant correlation was found between the high PRA found in the 75 pretransplant sera tested and the subsequent rejection episodes. In addition, the level of pretransplant PRA activity was associated with graft survival in that patients with low PRA had significantly superior graft survival than those with high PRA. Furthermore, the present data show that patients with historical high PRA, but current low PRA, had graft survival similar to that in recipients who had moderate PRA in their current sera. High PRA patients had more often a positive crossmatch than patients with low PRA. The PRA level was also associated with prolonged waiting period. Immunoglobulin class of antibodies was related to graft acceptance in that the presence of IgM antibodies was not detrimental to transplantation. The results in the present study suggest that PRA of < 10% is negligible, while more attention should be paid to patients with PRA > 10%.

Adolescent↗
PubMed2004

Minors come of age: Minor histocompatibility antigens and graft-versus-host disease.

Minor histocompatibility antigens (miHA) are responsible for the occurrence of graft-versus-host disease in the setting of a major histocompatibility complex matched sibling allogeneic stem cell transplantation. These miHA are peptide fragments that are associated with major histocompatibility complex class I or class II antigens. Elegant experiments have led to the molecular characterization of these antigens. Efforts to prevent graft-versus-host disease could be targeted through this pathway by matching for these miHA or by preventing antigen recognition. Alternatively, these miHA could be exploited as targets for a more potent graft-versus-malignancy effect. This area of miHA promises to continue to be an exciting area of continued research.

Antigen Presentation↗
PubMed2026

The combined impact of HLA and non-HLA mismatch between donors and recipients on kidney transplant survival: a genomic analysis in a prospective cohort.

BACKGROUND: Kidney transplantation outcomes are strongly influenced by immunological compatibility between donor and recipient. While genetic mismatches in the human leukocyte antigen (HLA) region have long been recognised as key determinants of graft survival, increasing evidence, including our own previous work, suggests that non-HLA alloimmunity also plays a critical role. METHODS: We sequenced exomes of deceased kidney donor and recipient pairs in the prospective kidney transplant cohort at the Vienna General Hospital, recruited between January 1, 2012, and June 15, 2023. Out of 1209 pairs, 1187 passed quality control for analysis. Non-HLA mismatch was computed by considering non-synonymous single nucleotide polymorphisms specifically encoding trans-cell membrane or secreted proteins in the kidney (nsSNP-tcmsk). Using adjusted Cox proportional hazards models, we replicated results from our earlier work in recipients with primary graft function after 90 days, and extended the analysis to the combination of nsSNP-tcmsk with eplet mismatch to assess their associations with graft loss in the full cohort. FINDINGS: Of 20,421 human proteins, 2371 were considered for the nsSNP-tcmsk score. In our replication analysis we estimated for nsSNP-tcmsk a hazard ratio (HR) of 1.33 (95% CI 1.02-1.74) for graft loss per increase of one interquartile range. The nsSNP-tcmsk and eplet mismatch were uncorrelated (Spearman correlation coefficient 0.02, p = 0.47). A composite score of nsSNP-tcmsk and eplet mismatch was associated with graft loss with a HR of 1.76 (95% CI 1.20-2.57) corresponding to an absolute difference in 7-year restricted mean survival time between the first and fourth quartiles of 0.52 years (95% CI 0.16-0.87 years). INTERPRETATION: The impact of non-HLA donor-recipient mismatch on transplant loss is of the same magnitude as established mismatch scores in the HLA region. Together, these scores may be further validated as guiding markers for the required strength of maintenance immunosuppression. FUNDING: Vienna Science and Technology Fund, NIH/NIAID.

Humans↗
PubMed1975

Acute myelocytic leukaemia and leukaemia-associated antigens in sisters.

In a sibship of 5 brothers and 7 sisters, 3 sisters died from acute myelocytic leukaemia while a 4th probably had the same disease. Laboratory studies on the close relatives revealed that a 5th sister had persistently high erythrocyte sedimentation-rates and serum-IgM levels and serological evidence of acute leukaemia-associated antigens. These findings suggest a possible preleukaemic state in this patient.

Acute Disease↗
PubMed1975

Lymphocyte-dependent antibody and renal graft rejection.

A patient with preformed cytotoxic lymphocyte-dependent antibody (L.D.A.) against the specific renal transplant donor rapidly rejected the grafted kidney. The characteristics of rejection were not those of hyperacute rejection due to cytotoxic complement-dependent antibody or of acute rejection is attributed to the cytotoxic activity of L.D.A. The avoidance of transplants based on positive crossmatches by the L.D.A. test or at least the carrying out of the L.D.A. crossmatch is advised.

Adult↗