Éva Gyódi

Levamisole-induced neutropenia and agranulocytosis: association with HLA B27 leukocyte agglutinating and lymphocytotoxic antibodies.

Among 37 patients treated with levamisole for rheumatoid arthritis (n = 19), for Reiters disease (n = 4) and for chronic articular brucellosis (n = 14) followed up during 6-12 months, 3 developed agranulocytosis and 3 severe neutropenia. Serum samples drawn before and during treatment were tested for leukocyte agglutinating and lymphocytotoxic antibodies. Leukocyte agglutinating antibodies were induced in 8 patients, in 5 of them in association with agranulocytosis or neutropenia. In 1 patient with agranulocytosis and in another one with neutropenia lymphocytotoxic antibodies were also induced. Two agranulocytotic and one neutropenic patient possessed HLA B27 antigen. In altogether 11 HLA B27 carriers the number of circulating neutrophils were significantly reduced during levamisole treatment when compared with those of patients lacking HLA B27 antigen.

Relations of HL‐A and Rh Systems to Immune Reactivity

HL-A, ABO, and Rh antigens, as well as different kinds of humoral and cell-mediated immune responses, were determined in 133 volunteers. These were selected from 463 subjects immunized with U ( D ) , or staphylococcus, or pertussis antigens according to their low and high immune responsiveness. HL-A and blood group antigens were correlated by a computer program to categorized immune parameters (low, medium, high values). The latter were correlated with each other. The only notable association of the immune parameters with HL-A antigens was found between HL-A 3 and 7 and spontaneous lymphocytotoxic activity in mouse fibroblast monolayer. A striking correlation was, however, found between R h antigens and a number of antibacterial antibody levels and parameters of cell-mediated immune responses. These correlations indicate that Rho(D)-positive subjects had rather high ‘natural‘ antibody levels and PHA-reactive lymphocytes. The latter were stimulated, however, only with high doses of PHA (PHA hyposensitivity) and they lacked spontaneous lymphocytotoxic activity. A reverse correlation was found in Rho(D)-negative subjects, the ability to produce anti-Rh,(D) antibodies being negatively associated with the level of some antibacterial antibodies. Natural antibody, immunoglobulin level and lymphocyte activity were significantly lower in males. Correlation was seldom found between categorized values of the individual immune parameters such as antibacterial antibodies, immunoglobulins, complement, and cellmediated immunity factors. Negative correlations were obtained between PHA hyposensitivity and a low antibacterial antibody level, and a positive one between IgA, complement level and lymphocyte stimulation. These results the Rh system may be associated with a gene or genes involved in immune response regulation.

Association between the lack ofHLA-DQw6 and the low incidence of multiple sclerosis in Hungarian Gypsies

In order to address the contradiction existing between high occurrence of HLA-DR2 and low incidence of MS in Gypsies, the distribution of the two subtypes of DQwl was determined in a Hungarian Gypsy population

Alloimmune and autoimmune background in recurrent pregnancy loss - successful immunotherapy by intravenous immunoglobulin.

Immunotherapies [leukocyte immunization, intravenous immunoglobulin (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have still controversial results in most clinical trials. A selection of these patients would be advantageous for higher efficacy.

Mixed lymphocyte culture--evidence that pretransplant transfusion with platelets induces FcR and blocking antibody production similar to that induced by leukocyte transfusion.

Experimentation clinique: les transfusions de plaquettes purifiees peuvent induire un «facteur bloquant» efficace avant transplantation (renale)

Remarkably Reduced Transplant-Related Complications by Dibromomannitol Non-Myeloablative Conditioning before Allogeneic Bone Marrow Transplantation in Chronic Myeloid Leukemia

A non-myeloablative conditioning protocol containing dibromomannitol (DBM/cytosine arabinoside/cyclophosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from sibling donors. Risk factors include: accelerated phase (10 patients), older age (17 patients over >40 years) and long interval between diagnosis and BMT (27 months on average). Severe mucositis did not occur. Venoocclusive liver disease was absent. Infectious complications were rare. Although grade II–IV acute graft-versus-host disease (GVHD) was present in 9 (25%) cases, there were only 2 serious (III–IV) ones. Chronic GVHD occurred in 25 (69%) cases, preceded by acute GVHD in 9 of the 25 affected patients. Early hematological relapse, 7–29 weeks after BMT, developed in 6 patients (17.6%). No relapse was noted in the completely chimeric patients, however molecular genetic residual disease was observed in 6 patients, in most of them after transient short-term mixed chimeric state. Overall actual survival rate is 83.3% for the 36 cases, and leukemia-free survival is 72.2% for the 34 engrafted patients.

THE ASSOCIATION OF HLA‐DR5 ANTIGEN WITH LONGER SURVIVAL IN CHILDHOOD LEUKAEMIA

belonged to blood-group 0, women 48% and men 36%, respectively. Although this difference was significant (x’= 12.66), no attention was paid to that. When summarizing data of Mustacchi et a1 with our results the high frequency of blood-group 0 in women with AL is very conspicuous. The possible genetically determined connection between blood-groups and susceptibility to AL might be a good explanation for the high frequency of group 0. Changes in blood-group characteristics of patients with AL in the course ofdisease are well known but it cannot be used for explaining sex differences in blood-group distribution.

Immunological importance of chimerism in transplantation: new conditioning protocol in BMT and the development of chimeric state

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisits to induce chimerism are immuno-suppression, myeloablation, or severe immunodeficiency of the recipients on the one side and donor originated immuno-hematopoietic cells in the graft on the other. The pathologic or special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion, and various kinds of solid organ grafting. Different types of chimerism are known including complete, mixed and mosaic, or split chimerism. There are various methods used to detect the type of chimera state, depending on the immunogenetic differences between the donor and recipient. The induction of complete or mixed chimerism is first determinated by the effect of myeloablative therapy. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of GVHD, and the rate of relapse. However, the most important contribution of the chimeric state is in development of graft versus leukemia effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

HLA and T-lymphocyte function in old age

The role of the major histocompatibility complex in the genetic control of reactivity of peripheral blood mononuclear cells (T lymphocytes) to lectins and allogeneic cells as a function of age was investigated. In randomly selected aged subjects the frequencies of HLA-A, B, and some C locus alleles did not differ significantly from those in the control group. However, some tendencies of haplotype frequency differences between young and aged subjects were found. Significant associations of impaired or preserved T-lymphocyte function could be detected in connection with some HLA-A (A3, A11) antigens only. The tendency of some phenotypic HLA-A and B or C and B antigen associations to be in correlation with impaired or preserved T-lymphocyte reactivity in old age seemed to be independent of their age-related frequency differences. In family studies of a partially inbred Hungarian population, differences were found in the rate of diminution of allogeneic reactivity in groups sharing different HLA haplotypes. Based on statistical analysis of these data, a genetic factor segregating with the MHC and taking part in the regulation of the age-dependent decline of T-lymphocyte reactivity can be postulated.

Selective effect of noncytotoxic blocking alloantibodies produced after platelet transfusions on MLC, and mitogen and soluble antigen-induced responses of human lymphocytes

The transfusion of blood components (buffy coat and platelets) may induce characteristic alloimmune response or suppressive regulation that have, in certain cases, a beneficial effect on allograft survival. The blocking effect of the sera of donors immunized with platelets on mixed lymphocyte culture and on the response of lymphocytes to mitogen as well as soluble antigen (PPD, tetanus toxoid) stimulation was studied. Six sera from 7 volunteers displayed a strong and significant nonspecific MLC blocking effect that was detectable on the 10th day following the second platelet transfusion (PT). Incubation of isolated stimulator and effector cell population with this “blocking sera” showed that the latter are involved in the mediation of suppression in the MLC test. This inhibitory effect is associated with the serum IgG fraction lacking any correlation with either class I or class II specific cytotoxic antibodies. Selective blocking behavior was found on transformation activity induced by mitogens or soluble antigens. Thus, sera of platelet-transfused volunteers decreases the responsiveness of lymphocytes to phytohemagglutinin, while the response to concanavalin A, tetanus toxoid, and PPD was not suppressed. Separate treatment of T and B lymphocyte populations and monocytes with the blocking sera showed that only T and B lymphocytes are targets, and not the monocytes for the inhibition in the case of PHA-induced proliferation. Indirect evidence may support the notion that MLC-inhibiting and FcR-blocking antibodies may be analog products of a regulatory alloimmune response induced by leukocytes that are partially responsible for the beneficial transfusion effect in organ transplantation.