Biomedical subjects
Publications and source records attributed to A H Waters.
Chloroquine stripping removes HLA antigens from neutrophils without damage to neutrophil specific antigens. This offers, for the first time, a simple procedure for the demonstration of neutrophil specific antibodies in sera that also contain HLA antibodies.
Evidence is presented for an inhibitory action of the bone marrow adherent cell layer on erythropoiesis in a case of pure red cell aplasia. Cultures of the patient's bone marrow with autologous and normal plasma showed normal numbers of CFU-C, but total absence of BFU-E. There was no inhibition of BFU-E when normal bone marrow was cultured with the patient's plasma. T-cell depletion of the patient's bone marrow did not affect these results, but after removal of the adherent cells, normal numbers of BFU-E were cultured. These observations suggest that the adherent cells, which are predominantly macrophages, were responsible for the inhibitory action on erythropoiesis.
This study shows that hitherto unexplained thrombocytopenia and neutropenia occurring after bone marrow allografting and autografting may have an immune basis. In the case of autografts, such antibodies are, by definition, auto-antibodies, and it is suggested that similar antibodies occurring after allografting are also auto-immune.
This study describes the development of autoimmune thrombocytopenia followed by autoimmune haemolytic anaemia in a Negro woman with measles. An IgM platelet autoantibody was detected using a fluorescent labelled antiglobulin technique. The thrombocytopenia resolved spontaneously, although the platelet autoantibody persisted and platelet survival remained shortened, suggesting a compensated thrombocytolytic state. An IgG granulocyte autoantibody was present transiently although the patient was never neutropenic. The haemolytic anaemia was due to an IgM cold autoantibody (anti-I), which was active up to 30 degrees C, and an IgG warm autoantibody, which was detectable only when she was severely anaemic. After an initial blood transfusion, the anaemia resolved and the red cell autoantibodies disappeared. The platelet, granulocyte and red cell autoantibodies were cell-specific and not a single cross-reacting antibody.
After bone marrow grafting, severe unexplained thrombocytopenia and granulocytopenia may complicate the post-graft recovery of the patient. The present study has shown the presence of antibodies to platelets and granulocytes of donor origin in recipients of both allogeneic and autologous bone marrow grafts. In the case of autografts, such antibodies are by definition autoantibodies, and similar antibodies after allografting may also have an autoimmune origin. It is likely that this is the result of transient immune system imbalance, common to both allo- and autografts, in the early post-graft period. The extent to which these antibodies affect the peripheral counts probably depends on the ability of the engrafted marrow to compensate for the rate of antibody-mediated cell destruction.
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A study of the effect of high-dose intravenous IgG in 25 adults with autoimmune thrombocytopenia confirmed the predictable rise in the platelet count seen during the infusion and previously reported in children. Unlike the data based on children, there was no sustained response unless the IgG infusion was closely associated with splenectomy. There was no correlation between the presence of platelet autoantibodies or the Ig class of the autoantibody and the pattern of response to the infusion. The initial platelet response appears to be the result of transient blockade of the reticuloendothelial system, including the macrophage Fc receptor mechanism. The long-term response in some patients requires another explanation and may be due to a more specific immunosuppressive effect of the high-dose IgG infusion. Splenectomy may have an additive effect by removing a major site of platelet autoantibody production.
Severe neutropenia may be a more common complication of high-dose penicillin therapy than previously recognized. This report describes five such patients, one of whom also had thrombocytopenia. The neutrophil and platelet counts rapidly increased on stopping penicillin, and the bone-marrow, which was hypocellular in some cases, became normal. Further studies on one of these patients, using a fluorescent antiglobulin technique with paraformaldehyde-fixed cells, demonstrated a complement-fixing IgG penicillin antibody reacting with the patient's granulocytes and platelets in the presence of the drug. This suggested an immune mechanism similar to the well-recognized penicillin-induced immune haemolytic anaemia. The associated bone-marrow hypoplasia may also be due to antibody-mediated suppression of penicillin-coated precursor cells.
Severe thrombocytopenia developed after an allogeneic bone-marrow graft in a 40-year-old woman in first remission from acute myeloblastic leukaemia. The thrombocytopenia had an autoimmune basis and was acquired from the bone-marrow donor who had an identical platelet autoantibody. The patient responded to high-dose intravenous IgG, and she has a normal platelet count 10 months after the graft. This study suggests that the immune defect in autoimmune thrombocytopenia can be transferred in cells capable of proliferating in a bone-marrow graft.
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A case of chronic cold haemagglutinin disease due to an IgM monoclonal (kappa) autoantibody with anti-M-like specificity is described in a patient with the MN phenotype. The autoantibody was present in very high titre and active at body temperature, but haemolysis was only mild. The direct antiglobulin test was positive due to C3d on the patient's red cells, and the autoantibody was able to bind complement to normal MM and MN cells with a marked dosage effect.
In a study of eight patients with Felty's syndrome, surface-bound immunoglobulin (IgG +/- IgM and complement) was demonstrated in all cases by a fluorescein-labelled antihuman globulin technique using paraformaldehyde-fixed neutrophils to prevent non-specific surface adsorption of immunoglobulin. The test was negative in control patients with rheumatoid arthritis alone. The neutrophil binding of immunoglobulin occurred in vivo and could not be reproduced with the patient's serum and normal neutrophils. The presence of alloantibodies due to previous pregnancy or transfusion can obscure this picture. A neutrophil autoantibody or cell-bound immune complexes may be the cause of this phenomenon, which may be a useful marker of Felty's syndrome in patients with rheumatoid arthritis.
A platelet cross-matching procedure has been assessed for selecting compatible donors for alloimmunized patients. This confirms the clinical value of combining an indirect platelet immunofluorescence test (PIFT) with a lymphocytotoxicity test (LCT) in predicting the survival of single-donor platelets. There was good agreement between the PIFT cross-match and post-transfusion platelet recovery. Compatibility in the LCT alone was insufficient for platelet donor selection, as this test did not detect all antibodies affecting platelet survival. Positive LCT and PIFT cross-matches indicated the presence of HLA antibodies. Inclusion of an indirect lymphocyte immunofluorescence test (LIFT) helped to classify the platelet antibody when the LCT cross-match was negative. In such cases, parallel positive findings with the LIFT and PIFT suggested a cytotoxic-negative antibody of probable HLA specificity active against platelets. Disparity between the LIFT and PIFT was also observed; a strongly positive PIFT along with a weak reaction in the LIFT suggested that a platelet-specific antibody was responsible for the poor platelet survival in these cases. This study has also shown the presence in multitransfused patients of LIFT-positive antibodies not reacting in the LCT and PIFT, which do not affect the survival of transfused platelets. A positive granulocyte cross-match was demonstrated in patients with febrile rigors associated with compatible platelet transfusions. Splenectomy and steroids may improve the survival of incompatible platelets depending on the nature of the platelet antibody.
Haemolytic disease of the newborn due to rhesus anti-e alone is a rare occurrence. This condition is described in the second child of an R2R2 mother who had not previously been transfused. The antibody was of IgG subclasses IgG1 + IgG3 and was detectable on the baby's cells for 4 months after birth. The anaemia was mild and persisted for the same period.
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The laboratory diagnosis of autoimmune thrombocytopenia has only recently become more satisfactory. In this study a fluorescein-labelled antiglobulin technique was used to investigate the immunochemical properties of the platelet antibody detected in a pregnant woman with severe thrombocytopenia. The antibody was autoimmune and appeared to have specificity for platelet antigens. It had both IgG and IgM components and did not fix complement. Steroids had a beneficial effect indicated by a return to normal of the platelet count, a falling antibody titre and the disappearance of detectable antibody on the patient's own platelets. Studies on the baby showed that the antibody had not crossed the placenta in detectable amounts.