Biomedical subjects
Publications and source records attributed to F H Claas.
Chimpanzees were allo-immunized with blood from donors, ChLA-A and -B identical to the recipient. The sera of some of these animals contained antibodies that reacted only with the platelets or granulocytes of the immunizing donor and of some related and unrelated chimpanzees. Both for the platelets and the granulocytes a di-allelic system of allo-antigens is described, provisionally called ChPL-1 and ChGR-1.
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To study the frequency and clinical importance of serum factors inhibiting CFU-c in patients with aplastic anaemia, sera from 21 patients were analysed. The sera of eight patients showed inhibition of at least one normal bone marrow, but strong and consistent inhibition of two or more normal bone-marrow samples was found in only two cases. In both of these two patients the inhibition disappeared after successful therapy. Fair, but not complete, correlation was found between serum inhibitors and HLA-antibodies, suggesting that at least part of these inhibitors are antibodies directed against HLA-antigens present on myeloid progenitor cells. Serum inhibitors appear to be infrequent in the population of patients with aplastic anaemia seen in our hospital and appear to have no major implications for therapy or outcome of the disease.
Recently we have shown that the induction of antibodies against the H-2 antigens after multiple platelet transfusions is due to leukocyte contamination of the platelet suspensions. Pure platelets are not able to induce a primary antibody response. The present study shows that the platelets, however, can be recognized by the immune system but they induce a suppression of the response. Mice pretreated with donor platelets will not give a primary antibody response upon a subsequent injection of donor leukocytes and the survival of donor skin grafts will be prolonged. Similar results were obtained by pretreatment of the responder mice with heat-treated donor leukocytes. Furthermore, repeated injections of heat-treated leukocytes of the recipient strain to the donor before bone marrow grafting, will delay graft-versus-host mortality. These data show that cells which have only class I antigens on their surface and no activating class II antigens, induce a suppression of the response against class I antigens.
When lymphocytes of healthy donors were incubated with penicillin and washed before HLA typing, the cytotoxic reactivity of some typing sera with their corresponding antigen was blocked. When the penicillin was added to the cytotoxicity assay at different times, competition between penicillin and alloantiserum for binding on or near the same epitope on the HLA molecule could be observed. On the basis of the inhibition experiments, HLA antigens can be divided into three groups: 1. Antibody reactivity blocked by penicillin (Bw35) 2. Antibody reactivity not blocked by penicillin (B14) 3. Antibody reactivity blocked by penicillin in some donors but not in others (A2). This third group may provide an opportunity to determine structural differences among, until now, serologically indistinguishable HLA molecules. By adding penicillin to a multispecific serum, containing both antibodies that can and cannot be blocked, a monospecific typing serum can be obtained. The differential effect of penicillin on the HLA antigens was not restricted to complement-dependent cytotoxicity on lymphocytes. Similar results were obtained when the HLA antisera were tested with indirect immunofluorescence on platelets or in absorption experiments.
A routine method has been developed and tested in the laboratory for the automatic reading of HLA typing and screening for antibodies with the microlymphocytotoxicity test. The assay is more sensitive than the NIH technique, is rapid, produces objective results, and can be easily linked up with existing manual procedures. Multipurpose reading machines are now commercially available.
Recently we could demonstrate that antibiotics can interact with polymorphic membrane determinants. As a result, these determinants can no longer react with their corresponding antisera (Claas et al. 1981, 1982). In the present experiments it was found that allogeneic cytotoxic T cells (CTLs), which were cultured in the presence of antibiotics, induced significantly stronger lysis against the specific target than CTLs which were cultured in the absence of antibiotics. In some cases the CML assay was only positive according to the European Workshop criteria when penicillin was added to the cultures, whereas the assay was negative in the absence of penicillin. On the other hand when CTLs were induced in an MLC culture without penicillin, lysis was higher against the target cell in the absence of penicillin than in the presence of penicillin. By adding penicillin to the effector phase, inhibition of lysis was observed. No difference in 3H-thymidine-incorporation was observed between MLC cultures with and without antibiotics. We conclude that antibiotics in the culture medium can influence the outcome of CML experiments.
Chronic benign neutropenia of infancy is a disease which develops a few months after birth and which is characterized by a severe selective neutropenia, accompanied by benign but persisting infections. The cause of the disease is still unknown. The sera from 5 such patients were tested for the presence of granulocyte antibodies as a possible cause of the disease. For the detection of these antibodies immunofluorescence, agglutination and granulocytotoxicity were used. All sera contained antibodies which reacted both with the neutrophils of one or both parents of the patient and a part of a panel of unrelated donors. From the reaction patterns against the panel we could identify the specificity of three sera. Two sera were directed to the neutrophil-specific antigen NA2, and the third one reacted with a hitherto not yet recognized neutrophil-specific alloantigen which we called NE1. In 4 patients we could confirm the autoimmune character of the disease by demonstrating the antibody on the patients' own granulocytes. These results suggest that autoimmunity may be the cause of many cases of benign infantile neutropenia.
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Of the 14 patients with aplastic anaemia treated in our hospital with anti-thymocyte globulin (ATG), four were refractory to random platelets before therapy due to the presence of leucocyte antibodies. In contrast to the ten nonrefractory patients in whom no success was obtained, three of the four refractory patients showed haematological improvement after ATG. Additionally, two patients could be substituted again with random platelets. The other two hardly needed platelet-transfusions after ATG, and they were given HLA-compatible platelets. To determine the degree of immunosuppression, these four patients were tested for the presence of antibodies against leucocytes and two endemic viruses, i.e., mumps and rubella virus. Before ATG, all sera reacted with almost the whole leucocyte testpanel. After treatment, the leucocyte antibodies disappeared completely in three patients. In one patient there was no dramatic change. In all patients, however, the antibody-titre against the mumps and rubella viruses remained constant and there was only a slight decrease in total IgG content in the three "suppressed" patients. We conclude that it might be worthwhile to study systematically the selective immuno-suppressive effect of ATG.
For the detection of platelet antibodies we developed an enzyme-linked immunosorbent assay (ELISA) on artificial monolayers of platelets in wells of micro-titre-U-trays. This simple and reproducible test can not only detect the presence and the specificity of platelet antibodies but also the class and subclass of the antibodies involved.
A newly developed enzyme-linked immunosorbent assay (ELISA) for the detection of platelet antibodies was compared with the platelet immunofluorescence test (PIF). A good correlation was found between both assays. However, ELISA seems to be more sensitive than PIF. Some sera reacted only in ELISA whereas no sera were found that were negative in ELISA and positive in PIF. When comparing the antibody titres, ELISA is at least 8 times more sensitive than PIF.
Preincubation of donor platelets with ticarcillin will prevent the reactivity of a platelet antibody against these platelets, whereas no influence was observed on antisera against HLA, 5A, 5b and ZWa. The implications for the mechanism of drug-induced antibodies with restricted specificity will be discussed.
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