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Biomedical subjects

E Gyódi

Publications and source records attributed to E Gyódi.

At least 19 recordsLinked to original sources

DNA typing revealing high HLA-Cw polymorphism completes availability of major histocompatibility complex loci in forensic medicine.

Studies of human population genetics in Hungary have revealed relevant heterogeneity in the major histocompatibility complex. In the present studies, two isolated ethnic groups were chosen: people living in the Káli Basin westward from the Danube River, and those living in Opusztaszer, a village eastward from Danube, who are known as native ancient Hungarians. Blood samples were collected from 70 people in the Káli Basin and from 45 people in Opusztaszer. The frequency of HLA-Cw alleles was determined by serology as well as by DNA typing in 46 and 32 samples of the two populations, respectively, and in 44 randomly selected subjects of Hungarian origin. Compared with a random population of cadaver donors (the deaths having resulted mostly from accidents or, in a smaller number, strokes or heart infarcts) and voluntary bone marrow donors (typed in the last 10 years) recruited from all parts of Hungary and representing the mixed Hungarian population, remarkable differences were found in haplotype and allele frequencies. HLA-A, -B, -Cw typing was performed by serology and, in the case of the HLA-Cw locus, by polymerase chain reaction (PCR)-SSP and/or PCR-SSOP techniques, as well. The PCR-SSO oligotyping procedure allowed the identification of 32 Cw alleles in contrast with the 9 serologically detectable types. Because of the combination of low antigen expression and the lack of specific serologic reagents of good quality, no HLA-Cw antigens were detectable in 41%, and only one was detected in 48%, of the investigated individuals by standard serologic typing. With PCR-SSO typing, however, 97% of the investigated individuals proved to be heterozygous for HLA-Cw alleles. The two isolated populations differed from each other, from mixed Hungarian and other Caucasian populations in HLA-Cw* allele frequencies, as well as in haplotype distribution. This newly recognized polymorphism at the HLA-Cw locus completes the availability of major histocompatibility complex typing in forensic science and practice.

Cadaver↗

[Genetic background of rheumatoid arthritis in connection with a family tree].

Authors present a rare history of a family with accumulation of autoimmune diseases. From eight siblings four had rheumatoid arthritis, one systemic lupus erythematodes, one primary Sjögren syndrome, and one Reiter disease. Interestingly, neither the parents nor the offsprings were affected. Because of the possible genetic background, the authors performed HLA serologic and DNA investigations in nine members of the family. The results showed, in agreement with data from the literature, the accumulation of HLA-DQ7 (DQB1*0301), DR4, B27 and DR6 (DR13) risk factors. This observation confirms, that the clinical and immunogenetic features are different in familiar and sporadic forms of rheumatoid arthritis. Authors summarize the genetic background of rheumatoid arthritis in connection with this family tree.

Adult↗

[HLA genomic tissue typing in myasthenic patients with rheumatoid arthritis].

In a 36 years old male and a 56 years old female myasthenic patient thymectomy was performed several years ago. In the male patient 5, and in the female patient 7 years after the operation rheumatoid arthritis developed. The rheumatoid arthritis in the male patient was seropositive with marginal erosions in the carpometacarpal and in the tarsometatarsal joints. The female patient had no joint destruction and was seronegative as well. The female patient had also an abnormal ratio between the separated CD4 and CD8 T-cells. The major histocompatibility complex determined by the serological methods revealed a haplotype of HLA-A1-B8-D3-DQ2, which is typically due to the myasthenic disease. In the female patient the molecular analysis of the HLA-D region showed a HLA-DRB1* 0401 allele, which is frequently associated with rheumatoid arthritis. The male patient had no allelic variant which could be related to his chronic disabilitating joint disease.

Adolescent↗

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.

Adolescent↗

[Clinical and immunopathological significance of chimerism in bone marrow and organ transplantations]

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisites to induce chimerism are immunosuppression, myeloablation or severe immunodeficiency of the recipients on one side and donor originated immuno-hematopoietic cells in the graft on the other. Special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion and various kinds of solid organ grafting. There are various methods to detect the type of chimera state depending on the immunogenetic differences between the donor and recipient. 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 graft-versus-host disease (GVHD), and the rate of relapse. However, the most important contribution of the chimeric state is the development of graft versus leukemia (GVL) 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.

Journal Article↗

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.

Antineoplastic Agents, Alkylating↗

[A new radiation-free conditioning in bone marrow transplantation and dibromo-mannitol therapy in chronic myeloid leukemia].

A new, radiation-free, conditioning protocol, containing the original Hungarian mitobronitol (DBM) (DBM/ cytosine arabinoside/cyclosphosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from HLA identical sibling donors between 1990-1997. In spite of some prognostically disadvantageous factors (half of them were above 40 years, 10 out of 36 patients were in accelerated phase, the disease history was longer than 2 years in average) the overall survival (30/36) and the leukemia free survival rate (26/36) were in accordance with the best international results. Transplantation-related toxicity was remarkably reduced in comparison to bone marrow transplantation performed by total body irradiation/cyclophosphamide (TBI/Cy) or busulphan/cyclophosphamide (Bu/Cy) conditioning protocols. Acute graft versus host disease was present in lower percentage (9/36) and the number of serious cases was only 2/36. Chronic GVH disease, generally known to be associated with antileukemic effect (GVL), occurred in 25 of cases. Early haematological relapse among the 34 patients with functioning graft occurred in 6 patients which rate is slightly higher than reported after TBI/Cy or Bu/Cy conditioning treatment. There was no relapse among patients transplanted within one year post-diagnosis and patients having CML with accelerated phase. The leukemia free post-transplant period was in association with the chronic GVH disease and full chimeric state.

Adolescent↗

Long-term related kidney graft survival in high-risk patients after monitored donor-specific transfusion protocol.

Altogether 57 patients were included in the related kidney transplantation program. Forty-four recipients were mixed lymphocyte culture (MLC) negative or slightly positive (SI < 7) against their mother/father donor, and most of them showed Fc gamma RII [erythrocyte antibody inhibition (EAI)] blocking antibody in their sera as the consequence of previous random transfusion. Thirteen patients showed significantly high MLC reactivity against their prospective parent donor (SI > 7) and had no EAI blocking antibody in their sera. The latter group was immunized either by buffy coat or purified platelets obtained from their donor in general two or three times at biweekly intervals. The indication for transplantation of donor-specific transfusion (DST)-treated patients was based on the appearance of EAI antibody and a significant reduction in the MLC reactivity (9 patients). DST patients had 100% kidney graft survival for 5 years and the DST untreated ones 75%. Suggested responsible factors for this observation are the haploidentity in HLA and the induction of suppressive immune regulation by DST.

Adult↗

Influence of HLA-DPB1 mismatches on MLR responses: the role of high resolution HLA class II typing and MLC in unrelated donor selection for BMT.

Twenty eight Hungarian patients lacking a compatible related donor and their 61 HLA-A,B,DR serologically identical potential unrelated donors (selected from BMDW) were investigated in this study. Out of the 61 donor-recipient pairs only 7 (11,5%) proved to be HLA-identical at DNA level. Thirty one pairs (50,8%) differed in DP alleles, 1 pair (1,6%) has a DQ mismatch only and 22 (36,1%) pairs differed in more alleles. More than one potential donor was found for 26 patients and 5 of them have several donors with DP mismatches only. Among the 31 donor-recipient pairs differing only in DP alleles, 0, 1 and 2 mismatches were observed in GvH direction in 7, 10 and 14 cases, respectively. In the MLC assay no proliferative response was observed when no DP mismatch has been found. Among the 1 and 2 DP mismatched cases 11 (35,5%) gave negative and 13 (41,9%) gave positive MLR results. We have found a large scatter in RR values. On the basis of the DNA typing and MLR results we have found that HLA-DPB1*0101-0201 stimulator-responder combination always gave negative MLR in both direction. HLA-DPB1*0201-0301 and DPB1*0301-0401 allele combinations were reactive in all cases. In conclusion MLC assay might indicate the low immunogeneicity in certain DP allele combinations as well as the avoidable positive combinations, which may help to select the best fitting donor for BMT.

Bone Marrow Transplantation↗

Association between long-term kidney graft survival and the presence of pre-transplant cytotoxic anti-HLA and/or non-MHC 'Fc gamma RII blocking' (anti-TLX) alloantibody.

One hundred kidney graft recipients were analysed retrospectively with regard to the presence of Fc gamma RII (EAI) blocking or cytotoxic HLA antibody induced by pretransplant transfusion. Previous studies suggested that transfusion induces the production of EAI blocking antibody which may have specificity to TLX/CD46/MCP alloantigens. A superior graft survival (65%/9 yr) was found in the presence of EAI alloantibody compared to graft survival in the absence of this antibody (40%/9 yr). Further analysis showed the following survival rates in relation to the combined appearance of HLA cytotoxic and EAI antibody (EAI positive, HLA negative 67%/9 yr; EAI positive, HLA positive 60%/9 yr; EAI negative, HLA positive 0%/9 yr; EAI negative, HLA negative 40%/9 yr). There was striking low graft failure in the first 6 months in patients with EAI antibody. Taking into consideration that the HLA B/DR mismatching grade in all various groups were the same and no considerable difference was found in association to graft survival, the presence or absence of alpha EAI (anti-TLX) antibody solely seems to have superior or additional effect on graft survival as compared to HLA matching.

Antibodies, Anti-Idiotypic↗

The polymorphic human TLX-B/CD46/MCP system and its implications in transplantation and reproduction.

TLX antigens have been found on most peripheral blood cells, trophoblasts, seminal vesicle cells and sperms. These antigens seem to be associated with the membrane cofactor protein (MCP) and the CD46 antigen. Alloantibodies to TLX antigens with Fc tau RII-blocking features were obtained by transfusion of leucocytes or platelets. Preliminary population studies revealed that alloantibodies to TLX/CD46/MCP recognize four overlapping specificities. The terminology TLX-B was introduced with specificities TLX-B1, B2, B3, B4 and frequencies obtained in the population were: 38%, 46%, 42% and 26%, respectively. Family studies showed an independent segregation of the TLX and HLA alleles. At the cellular protein on trophoblast, the alloantibody detected a glycoprotein of 66-67 kDa molecular mass, which may correspond to the alpha chain of the TLX/CD46/MCP isotypes. A direct association of the alloantibody with Fc tau RII could be excluded thus its FcR blocking feature is probably based on an indirect functional effect. After transfusion and in pregnancy the induction of TLX alloantibody production depended on the mismatching in the TLX/CD46/MCP phenotypes. Probable associations were revealed in the case of recurrent habitual abortion between the lack of Fc tau R blocking antibody production and the matched TLX specificities of the couples. After transfusion, TLX alloantibody production with Fc tau R and MLR blocking function was induced only when the recipient was lacking the TLX specificities expressed on the donor cells. Suppression of MLR was found only when TLX specificity in sera corresponded to the TLX specificity of the effector cell. The immunopathological importance of these findings in transplantation and reproductive medicine has yet to be clarified.

Abortion, Habitual↗

Clinical significance of longitudinal complement measurements in recipients of bone marrow transplant.

Overall activity of classical complement pathway, C3 and C4 levels, level of circulating immune complexes and concentration of serum immunoglobulins were measured in 38 patients transplanted with HLA-identical bone marrow before and after transplantation for at least 4 years. Changes of complement parameters and their association with acute and chronic GVHD and with infections were analysed. A strong association was found between the development of chronic GVHD and hypercomplementaemia measured in 16 long-term survivors. Low pre-transplantation C4 activity was found to predict the development of severe acute GVHD. These findings indicate that longitudinal complement measurements may have clinical value in BMT patients.

Acute Disease↗

Hereditary triosephosphate isomerase (TPI) deficiency: two severely affected brothers one with and one without neurological symptoms.

A 13-year-old Hungarian boy (B.J.Jr.) with congenital haemolytic anaemia (CHA) and hyperkinetic torsion dyskinesia was found to have severe triose-phosphate isomerase (TPI) deficiency. One of his two brothers (A.J.), a 23-year-old amateur wrestler, has CHA as well, but no neurological symptoms. Both have less than 10% TPI activity and a highly increased dihydroxyacetone phosphate (DHAP) level in their red blood cells. Their TPI had a slow electrophoretic mobility and was heat unstable. Both parents and a third brother are healthy heterozygous carriers of the defect. A.J. represents a unique phenotype from the point of view that all published "homozygotes" had severe neurological alterations from infancy or early childhood except one infant who died at 11 months, probably too young for neurological symptoms to be noted. In contrast to the two affected Hungarian brothers all but one "homozygote" has died before the age of 6 years. The striking difference in the clinical course of the defect between the two brothers with the same severe red blood cell enzyme deficiency may originate from unusual differences between two double heterozygous brothers resulting inter alia in different levels of TPI expression in various tissues. Significantly lower TPI activities were found in both the T- and B-cells of the propositus as compared to the respective cells of the neurologically symptom-free brother.

Adult↗