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Biomedical subjects

A van Leeuwen

Publications and source records attributed to A van Leeuwen.

At least 19 recordsLinked to original sources

Major histocompatibility complex-restricted antibody reactivity mainly, but not exclusively, directed against cells from male donors.

An IgM antibody, present in the serum of a female patient with aplastic anemia, is described that reacted in a modified complement-dependent cytotoxicity test with a subset of the B cells from HLA-A2-positive, but not HLA-A2-negative males. With the exception of two HLA-A2 positive females, the antibody did not react with other cells from either HLA-A2-positive or HLA-2-negative females. The cells of one of these and from HLA-A2-positive males were able to absorb the antibody from the serum. Cells from other donors were unable to absorb the antibodies. The mononuclear cells of the same patient were cytolytic in cell-mediated lympholysis (CML) for phytohemagglutinin blasts from all HLA-A2-positive males and one of the females reacting with antibody, but not with blasts from HLA-A2-negative males and all other females. Thus, the results obtained with the antibody in the complement-dependent cytotoxicity test showed an almost perfect correlation with cytolysis in CML tests. These results suggest that the IgM antibody may be the first example with major histocompatibility complex restriction. Because the antibody reacted with the cells from two female donors, the restricting determinant is not, in all probability, the H-Y determinant.

Anemia, Aplastic

Influence of matching for HLA-DR antigens on skin graft survival.

HLA-DR typing results of 47 skin transplant donor-recipient pairs were analysed. HLA-A, B, and C typing and mixed lymphocyte culture (MLC) testing was also included in this study. Skin transplants exchanged between HLA-A-, B-, and DR-identical, MLC-negative donor-recipient pairs had the longest graft survival (mean survival time, 17 days), whereas skin grafts exchanged between completely nonidentical donor-recipient combinations had the shortest survival (mean survival time, 10 days). Because of the correlation between identity for the DR antigens and the low or nonreactivity in the MLC test, identity for DR will predict a better skin graft survival than nonidentity. It was concluded that the best match between donor and recipient of a graft, using only serological techniques, is one where there is identity for HLA-A, B, and DR.

B-Lymphocytes

Antibodies directed against antigens on the endothelium of peritubular capillaries in patients with rejecting renal allografts.

This study was undertaken to examine the humoral immune response against endothelial antigens of the donor kidney in human renal allograft recipients. Sera from 61 transplant recipients who received 62 grafts were studied for the presence of circulating endothelial antibodies (CEAb) using an indirect immunofluorescence technique with a pretransplant biopsy of the graft as a substrate. IgG antibodies directed against the endothelium of peritubular capillaries were found in the sera of 6 of the 10 patients with graft rejection within 7 weeks after transplantation, whereas these antibodies were not found in the absence of rejection (P less than 0.001). Immunofluorescence studies of post-transplant biopsies showed IgG along the endothelium of peritubular capillaries only in the grafts of patients with CEAb. Eluates from these grafts contained IgG antibodies that bound to the endothelium of the donor as shown by the indirect immunofluorescence technique. Absorption of endothelial antibody (EAb)-positive sera with human platelets or Wistar strain rat erythrocytes showed that the EAb were not directed against serologically defined HLA antigens or against heterophile antigens on rat erythrocytes. We conclude from this study that the presence of antibodies directed against endothelial antigens is associated with poor graft prognosis and that these antibodies may be responsible for the rejection process.

Animals

Matching for HLA antigens of A, B, and DR loci in renal transplantation by Eurotransplant.

79 patients and their respective cadaveric kidney donors were typed for HLA-A, HLA-B, and HLA-DR antigens using frozen stored spleen lymphocytes and fresh peripheral-blood lymphocytes. The kidney-graft survival-rate at 3 to 18 months was highest when donor and recipient shared one or two DR antigens and three or four A and B antigens. The graft-survival rate was significantly higher (87 +/- 6%) at 18 months in these patients than in less well matched patients (48 +/- 9%).

Epitopes

Platelet transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence tests.

Although the value of HLA matching for the selection of platelet donors for patients refractory to random platelets is beyond doubt, even perfectly matched combinations sometimes fail to give a satisfactory transfusion response. With HLA typing and negative lymphocytotoxicity crossmatches, 35% of the platelet transfusions administered to 15 patients gave disappointing results (29 of 82). Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7% (6 of 82). Five of these failures were observed in one patient. The target of the antibodies detected with this platelet fluorescence test is not yet fully specified. It seems probable that both HLA and platelet-specific non-HLA antibodies were detected. No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found.

Blood Donors

First experiences with HLA-matched corneal grafts in high risk cases.

In highly vascularized corneas the number of graft failures caused by irreversible rejections is higher than in non-or slightly vascularized corneas. The importance of antigen compatibility is demonstrated, especially in these 'high risk' cases. Ten highly vascularized corneas were grafted with HLA-matched donor material; only one reversible rejection was seen in this group. Nine non-or slightly vascularized corneas were grafted with donor material chosen a random. Retrospective HLA matching was performed. Three irreversible rejections were seen in this group. The number of HLA incompatibilities was high.

Corneal Transplantation

Evidence for two series of B-cell antigens in man and their comparison with HLA-D.

Population and family studies of five sera with antibodies against B-cell determinants show an excellent fit of some of them with the HLA-D determinants, suggesting that the HLA-D determinants themselves or closely linked structures can be recognized by serology. One serum, Ag, might be coded for by a locus different from HLA-D, which could be located between HLA-A and -B. A two-color fluorescence test to detect B-cell antigens was used and found to save time and reagents and to give very good results.

B-Lymphocytes

Inhibition of the mixed leukocyte reaction by alloantisera in man. II. Incidence and characteristics of MLC-inhibiting antisera from multiparous women.

The incidence of MLC-inhibiting antibodies was determined in 42 pregnancy sera. MLC's were carried out between the cells from the serum donor and her husband in the presence of nonimmune AB serum and the test serum. Fifty per cent of the sera reduced the MLC response to less than 40% of the control values. Only four sera had lymphocytotoxic activity. The inhibition was strong against the specific immunizor, less strong against random unrelated cells and weak against cells which were SD-identical with the serum donor. Absorptions with lymphocytes and platelets were carried out. Lymphocytes removed activity in three of the four sera tested. Platelets removed activity from one serum. It was concluded that both anti-LD and anti-SD antibodies were able to inhibit the MLR at the stimulator cell level.

Cytotoxicity Tests, Immunologic