Significant factors influencing kidney graft survival.
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Biomedical subjects
Publications and source records attributed to F H Claas.
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Repeated platelet transfusion to thrombocytopenic patients frequently induce anti HLA antibodies, which are responsible for transfusion refractoriness. As the transfused platelet suspensions usually contain 15-30% of the leukocytes originally present in the blood, it is not known whether these antibodies are raised by the platelets or by the contaminating leukocytes in the platelet suspensions. In the mouse, pure platelet suspensions are not able to induce a primary antibody response, as measured by the NIH test and the indirect immunofluorescence test on platelets and leukocytes, despite repeated injections. However, when the platelet suspensions are contaminated with leukocytes (10(3) or more/injection) an antibody response is induced. This response is higher than the response indiced by an equal amount of leukocytes alone. As in man the use of leukocyte poor platelets postpones the development of refractoriness to random platelets it is concluded that transfusions with leukocyte free platelets will probably prevent immunization against the HLA antigens.
Acidic eluates from two rejected kidney allografts contained antibodies reacting only with the endothelial cells and the monocytes of the specific kidney donors. No reaction was observed with the B-cells or the T-cells of these donors. When these eluates were tested against the leukocytes of healthy blood donors that were typed for HLA-A, -B, -C and DR, positive reactions were observed with the monocyte but not with the lymphocyte fraction. The first eluate reacted with 6.4% of the donors and the second eluate with 38.3%. No correlation with any of the HLA-A, -B, -C or DR antigens was found. If a more extended study proves that the endothelial-monocyte antigens do play an important role in kidney transplantation, matching of donors and recipients for these antigens and cross-matching recipient serum with donor monocytes may become a necessity in the future.
Although granulocyte transfusions and bone marrow transplantation are becoming common clinical modalities, our knowledge of surface nonerythroid, nonlymphoid, non-HLA hematopoetic antigens remains very incomplete. Accordingly, we have systematically screened sera from recipients of multiple granulocyte and whole blood transfusions, and immunoneutropenic patients for antibodies directed primarily at granulocytes. The initial screens demonstrated that >50% of the sera from the above sources contained non-HLA cytotoxic and/or agglutinating antibodies. Preliminary clustering indicated seven possible new specificities detected by microgranulocytotoxicity. Calculations for Hardy-Weinberg goodness of fit based on a study of 98 unrelated donors plus informative families established that 5 of these were alleles of a single new locus termed Human Granulocyte Antigen (HGA)-3a, b, c, d, and e. Absorptions indicated that these antigens were present on mature granulocytes but absent from platelets, lymphocytes, monocytes, and myeloid precursors. A single antigen of another separate locus, HGA-1, was also identified. Absorptions revealed a quite different distribution for HGA-1 than HGA-3, this antigen being detected on monocytes and myeloblasts as well as on mature granulocytes. Independent segregation of the three loci from HLA, from the NA-NB and the 5a-5b antigens, and from themselves was confirmed in informative families.Finally, it seems likely that other antigens will be identified because several other sera that react with both monocytes and granulocytes have been detected.
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Diminished survival of transfused platelets occurred in two patients given co-trimoxazole, and a third patient taking this drug developed thrombocytopenia. By means of an indirect immunofluorescence assay antibodies against donor platelets coated with co-trimoxazole were found in the sera in all cases. These antibodies were directed against the trimethoprim component of co-trimoxazole and not against sulphamethoxazole. Co-trimoxazole is a potent antimicrobial agent and is advocated for treatment and prophylaxis in leukaemia. Hence its adverse effect on platelets is of great importance.
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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.
Mice of two congenic inbred strains C3H/Sn (H-2k) and C3H.B10 (H-2b) were infected with 100 Schistosoma mansoni cercariae. After the infection, the following parameters for the immunological response were studied: worm burden, mortality, antibody titre, spleen index, eosinophilia, delayed type of hypersensitivity and in vitro response to three S. mansoni antigen preparations. No difference in the worm burden and in the in vitro response to the antigen preparations of adult worm antigen, soluble egg antigens and the egg antigen MSA1, was found. The C3H.B10 mice showed a significantly higher mortality, antibody titre and delayed type of hypersensitivity while the C3H/Sn mice showed asignificantly higher spleen index and eosinophilia. This indicates that the H-2 region influences the course of an acute S. mansoni infection, whereas the susceptibility to the infection seems not to be influenced, as is shown by the worm burden.
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Sera of 97 consecutive transplant recipients were studied for the presence of antibodies directed against their renal allografts. A highly significant correlation (p less than 0.001) was found between irreversible rejection and donor-specific endothelial antibodies (EAb). EAb reacted not only with the endothelium of peritubular capillaries and venules, but also with glomeruli. Absorption of EAb to platelets, B- or T-lymphocytes did not remove its EAb activity or its cytotoxicity for monocytes. Furthermore, it was shown with a panel of randomly chosen donor kidneys, that EAb are directed against a polymorphic system of endothelial-monocyte antigens, which is unrelated to HLA-A, -B, -C or -D.
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Fifty cases of nitrofurantoin-associated hepatic injury and two cases of nifurtoinol (hydroxymethylnitrofurantoin)-associated hepatic injury reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs were analyzed in detail. In 38 cases, a causal relationship was considered likely [i.e., "highly probable" (n = 4), "probable" (n = 23) or "possible" (n = 11)]. In 25 cases, hepatic injury was of the acute type whereas 13 cases presented a chronic type of reaction. Both types were more common in the elderly. Eighty per cent of the acute reactions appeared within the first 6 weeks of treatment and were sometimes accompanied by fever (28%), rash (12%) and eosinophilia (16%). Biochemically, the pattern was mainly hepatocellular (32%), whereas mixed cholestatic-hepatocellular (4%) and cholestatic (4%) patterns were uncommon. Although mild to moderate liver enzyme elevations (60%) were common, these were primarily symptomatic. The reaction was fatal in one "acute" and one "chronic" case. In the chronic cases, nuclear (82%) and smooth muscle (73%) antibodies and LE cells (50%) were frequently present. HLA typing showed no increase of the HLA B8 or HLA DRw3 haplotype. HLA DR2 (56%) and HLA DRw6 (56%) were more frequent than in controls (both 29%), but this was not statistically significant. Histology showed mainly necrosis, varying from spotty to massive, in the acute cases and a pattern consistent with chronic active hepatitis in the chronic cases.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of genetic and environmental factors on the functional cytotoxic T cell (CTL) allorepertoire was studied by comparing the CTL precursor frequencies against the same HLA alloantigens in 116 sibling pairs. A significantly different precursor frequency was found in 68%, 61% and 59% of siblings sharing 0, 1 and 2 HLA haplotypes, respectively. These data show that, although HLA is important in determining the T-cell repertoire, this is hardly reflected in the allorepertoire. Even 50% of the monozygotic twin pairs showed a significant disparity in their CTL allorepertoire, indicating that environmental factors play a role as well. The non-inherited maternal HLA antigens could be identified as one of the environmental factors shaping the CTL allorepertoire.
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