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Biomedical subjects

J J van Rood

Publications and source records attributed to J J van Rood.

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

Human skin grafts from mixed lymphocyte culture-positive donors provide help for the rapid rejection of simultaneously transplanted skin grafts from mixed lymphocyte culture-negative donors.

The influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood.

Graft Rejection

Influence of previous immunization on skin graft survival.

The results of skin grafts transplanted in immunized and nonimmunized recipients was analysed. Specific sensitization for HLA-A or B determinants shortens graft survival if the recipients were immunized by s.c. injections of leukocytes. When the recipients had been pregnant, no such influence of specific HLA-A or B sensitization could be demonstrated. The variance in mean survival times of grafts exchanged between mixed lymphocyte culture (MLC)-positive donor-recipient combinations was significantly smaller than the variance in mean survival time (MST) of grafts exchanged between MLC-negative combinations. This difference could be the result of the influence of allograft immune-activating determinants of different strength in the MLC-negative donor-recipient combinations. Also the variance in MST of grafts in immunized recipients was significantly larger than the variance in MST of grafts in nonimmunized recipients. Apart from the obvious effect of HLA-A and B sensitization, other less well documented factors must have influenced graft survival. We did not find evidence for a graft enhancing effect of B cell-specific antibodies.

Antibodies

NE1: a new neutrophil specific antigen.

The sera of three children with chronic benign neutropenia, due to anti-neutrophil antibodies, were studied with respect to their antibody specificity. This was done by screening the sera against a panel of leukocyte donors in the EDTA micro-agglutination test and in the indirect fluorescence test. Two of the sera contained antibodies against the known neutrophil-specific antigen NA2. The third serum was directed against a new neutrophil-specific antigen. Genetic analysis showed no correlation between this antigen and the already known neutrophil-specific antigens: 9A, NA1, NA2, NB1, and NC1. In the Dutch population the frequency of the new antigen, tentatively called NE1, is 23%, which gives a gene frequency of 0.12.

Agglutination Tests

Genetic control of survival in epidemics.

Descendants of Dutch colonists, who emigrated to Surinam in the last century and survived epidemics of typhoid and yellow fever with a total mortality of about 60%, were tested for twenty-six polymorphisms. The gene frequencies were compared with those of a large Dutch control sample. An analysis of drift indicated that the variations in gene frequencies observed for C3, Gm, HLA-B, and GLO were unlikely to be due to drift. Therefore these data might indicate selection through genetic control of survival in these epidemics.

Blood Group Antigens

Cadaveric graft survival, clinical course, blood transfusion, HLA (A and B) match, and DR match in adult patients transplanted in one centre.

The influence of blood transfusions, HLA, A and B, DR matching was studied in adult patients transplanted in one centre. The conclusions were: 1. Pre-transplant blood transfusion(s) are a prerequisite for graft acceptance. 2. In transfused patients with no HLA A and B mismatch, there is only 8% graft loss due to irreversible rejection. 3. In transfused patients with a functioning graft after six months, a decrease in the number of reversible rejection crises is observed in patients with no HLA A and B mismatch or with identity for HLA B7 or HLA B8. 4. Identity for HLA B7 or B8 also gives a higher chance of a late onset of the first rejection crisis.

Antibody Specificity