Comparison of pretransplant serum alloreactivity estimated by immunoenzymatic assay (PRA-STAT) and lymphocytotoxic test in renal transplant recipients.
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Adult↗
Biomedical subjects
B Nowakowska
Publications and source records attributed to B Nowakowska.
[[Chimerism and tolerance].
The goal of transplant immunology since its beginnings has been, and continues to be, the induction of long lasting unresponsiveness to a foreign graft. Although the transplantation of solid organs and cellular grafts is already a clinical routine, life-long nonspecific immunosuppression is still required to maintain the graft. Malignancies, opportunistic infections and organ toxicity are the main limitations of the antirejection therapy. One approach that finally could make the dream of tolerance induction come true, is hematopoietic chimerism. Hematopoietic chimerism is defined as the coexistence of donor and host hematopoietic cells in the recipient's system. This coexistence might induce the mechanisms of central or peripheral tolerance to foreign, donor's antigens. The aim of this paper is to present current knowledge about relationship between the state of macro- or microchimerism and transplantation tolerance in bone marrow and organ transplantations.
Animals↗
[The effect of occupational exposure to metallic mercury on selected parameters of hemostasis].
The group investigated comprised 60 workers under conditions of chronic exposure to metallic mercury vapours (mean exposure duration--9.3 yrs; mean age of subjects--38.5 yrs). The control group was composed of 24 non-exposed persons (mean age--39.9 yrs). The workers exposed were divided into three groups according to the air concentration of metallic mercury vapours at the workpost, group A--0.15-0.17 mg/m3, group B--0.03-0.08 mg/m3 and group C--0.02-0.03 mg/m3. The workers qualified for the study did not receive any medication containing acetylsalicylic acid derivatives, and did not consume alcoholic drinks for few days prior to the study. Persons with the diagnosis or the history of blood disorders, venous or arterial thrombosis as well as those with diabetes and hyperlipidaemia were excluded from the study. The haemostasis assessment was based on the results of laboratory tests, PLT, TBT, ACT, APTT, HTCT, INR and Fg, AT III, alpha 2 M, FDP, and FM concentrations. The comparison of the exposed and control groups revealed a statistically significant decrease in ACT and AT III concentrations. When particular groups under exposure were compared with one another and the controls, the increased INR and Fg concentrations were found in group A. Moreover, this group showed an increased platelet count, as well as decreased TBT and alpha 2 M concentrations. However, the differences between the groups were statistically insignificant. The results of the study indicated that chronic exposure to mercury may impair haemostasis and lead to hypercoagulability. The latter may result from the deficiency of natural coagulation inhibitors.
Adult↗
Labour force. Outlook to the year 2020 according to the current Central Statistical Office forecast.
"The paper deals with the changes in the number and structure of population of working age in Poland and by voivodeships to the year 2020 as presented by the most current demographic forecast of the Central Statistical Office. The period 1995-2020 is going to be characterised, in its first stage, by a serious increase in the number of population of working age and then, after the year 2010, the size of this group will considerably contract.... The changes flagged will vary geographically."
Age Distribution↗
A new lymphoblastoid cell line defective in class II HLA expression.
A lymphoblastoid cell line, HAJ, was derived by in vitro transformation with Epstein-Barr virus of peripheral blood lymphocytes (PBL) from a patient with renal insufficiency awaiting kidney graft. Cell surface expression of class I and class II HLA molecules was determined by flow cytofluorimetry using monoclonal antibodies and compared with that of cell line PAJ similarly derived from a healthy donor. HAJ cells expressed class I antigens at levels comparable with PAJ cells. In contrast, class II antigens were absent from the cell surface of HAJ cells while they were abundant on PAJ cells. Permeabilization and fixation of cells with acetone/formaldehyde solution revealed intracellular Ki-67 antigen but not class II HLA molecules. The genes for HLA-DR beta, DQ alpha and DP alpha were present in the HAJ genome as detected with polymerase chain reaction (PCR) using locus-specific primers amplifying a second exon. In RT (reverse transcriptase)-PCR, transcripts of DQA1 and DPA1 genes were easily detectable in PAJ (positive control) but not in HAJ cells. These results suggest a defect in HAJ cells of transcription of genes for all class II antigens. The cell line HAJ may prove to be an interesting model for in vitro studies of molecular mechanisms of the regulation of class II expression.
Biological Transport↗
[Problems with donor-recipient matching in kidney and bone marrow transplantation].
The main problem in matching donor-recipient pair in kidney transplantations is sensitization of dialysed patients. The patients with high percentage of cytotoxic antibodies to peripheral blood lymphocytes from a random panel, have a low chance of receiving a renal allograft. Negative results of the crossmatch between recipient serum and donor lymphocytes is decisive criterion for kidney transplantation. However not all antibodies are harmful for the graft. We present out methods of differentiating between auto- and alloantibodies and between IgM and IgG class of alloantibodies in sera of hypersensitized patients. The precision of identification of HLA matched donors is vital in bone marrow transplantations. The standard cytotoxicity tests cannot identify all HLA class II alleles and MLC testing is a long procedure. We present our observations from introducing the PCR Fingerprinting technique for a rapid identification of the class II compatible individual among potential donors bone marrow transplant.
Autoantibodies↗
[Effect of recombinant human erythropoietin on kinetics of alloantibodies in patients awaiting renal allograft].
Iterative transfusions are one of the most important mechanism of the induction as well as maintenance anti-HLA antibodies. We evaluated the evolution of PRA (panel reactive antibodies) in 46 sensitized patients during and after withdrawal of blood transfusion. Twenty nine of them (22 women and 7 men in age 38 +/- 7 years) were treated with EPO for 13 to 60 months. With EPO therapy anemia improved, allowing transfusions withdrawal in 19 patients. PRA level decreased from 62 +/- 23% to 42.5 +/- 25% after 1 year of therapy. At 2 year PRA reduced to 37.7 +/- 30% and remained on this level at 3 year. PRA levels became negative in 4 patients, decreased in 11 (by 35%) and remained high in 7 patients. The results of the patients were compared with 17 sensitized patients (9 women, 8 men in age of 40 +/- 10) who did not receive EPO and only part of them required sporadicly transfusions (mean 3 unit of blood) during last 2-3 years. PRA levels decreased from 59 +/- 20% to 45 +/- 22% at 3 year. PRA became negative in 6 patients. The reduction in PRA levels in this group of patients was lower than in EPO treated patients (24.3% vs 14%) as well as in fewer number of patients PRA droped (53% vs 63%). Analysis of risk factors for persistent high levels of alloantibodies showed, that female sex and DR2 phenotype were significant factors.
Adult↗
Absorption with K562 erythroblastoma cells as a means for discrimination between auto- and alloantibodies in sera of hypersensitized renal patients.
We applied K562 erythroblastoma cell line as a substitute for autologous lymphocytes in the absorption of autoantibodies from sera of 26 hypersensitized renal patients exhibiting high degree of cytotoxic reactivity with a panel of lymphocytes from unrelated individuals (panel reactivity, PRA). All of analysed sera contained allo-reactivity before absorption. After removal of autoantibodies, 85% of the sera still contained alloantibodies whereas in 15% of the sera no alloreactivity was detectable. Absorption of high PRA sera with K562 cells and with autologous lymphoblastoid cell lines derived by transformation with Epstein-Barr virus (EBV-LCL) gave substantially the same results. As autoantibodies have reportedly no effect on kidney graft survival, the autoabsorption of high PRA sera may increase the chance of patients in whom only autoantibodies were detected to receive the transplant. Application of K562 cells, instead of autologous lymphocytes/lymphoblasts, is recommended whenever high numbers of patient's cells are not available. It may be particularly suitable for routine clinical laboratories, not equipped and prepared for derivation and propagation of EBV-LCL.
Adult↗
Determination of immunoglobulin class of alloantibodies in sera from hypersensitized renal patients.
26 sera from hypersensitized renal patients were analysed for immunoglobulin class of alloantibodies. To assess the participation of IgM and IgG in alloreactivity, sera were treated with dithiothreitol (DTT) or Staphylococcus aureus protein A (SpA), respectively. Treatment with both DTT and SpA was also performed to test the possible contribution of other immunoglobulin classes. Immunological complexes which may mimic alloreactivity were excluded by polyethylene glycol (PEG) treatment. Immunochemically modified sera were tested against a panel of allogeneic B and T lymphocytes. IgG class alloantibodies reactive with B lymphocytes were found two times more frequently than those reactive with T lymphocytes. In 22% of sera only IgM alloantibodies were detected. No contribution of other immunoglobulin classes of immune complexes was seen. Our results show that DTT and SpA treatment are technically simple and reproducible methods of discriminating between IgG and IgM alloantibodies and can be recommended for routine use in clinical analysis of sera from hypersensitized renal patients awaiting kidney graft.
Adult↗
HLA-DR antigens in children with mumps meningitis.
The frequency of HLA-DR antigens was studied in 54 patients with mumps meningitis, and in two control groups. The first control group comprised 333 randomly chosen subjects while the second group was composed of 46 subjects who have passed mumps without meningitis. The DR5 antigen was more frequent in patients than in the second control group with relative risk of 2.4 and significance at the level of p < 0.05. The p value became insignificant after the correction for the number of antigens investigated.
Child↗
HLA-A, B, C, and DR gene and haplotype frequencies in 600 poles by a maximum likelihood method of gene counting.
A population sample of 600 healthy, unrelated persons was used for estimating HLA-A, B, C and DR antigen, gene and haplotype frequencies. The Polish population is characterized by a high value of HLA-A10, B13, B27, DR1 and DR5 gene frequencies. Strong gametic associations between genes A1 and B8, A3 and B7, as well as between B8 and DR3, and B7 and DR2, typical for many European populations, are also present in the Polish population.
Adult↗
Blood transfusions and the development of cytotoxic antibodies in dialyzed patients.
In our work we investigated factors which can influence the alloimmunization and especially the ranges of cytotoxic antibodies that develop in patients on dialysis awaiting their first graft. Up to 15 liters of administered blood the proportion of immunized patients is rather stabile, not exceeding 50%. After further transfusions the percentage of immunized patients is growing rapidly reaching about 85%. Hyperimmunization, marked by cytotoxic antibodies with more than 80% panel reactivity is significantly more frequent in patients who obtained 15 and more liters of blood. In females the hyperimmunization is about 4 times more frequent than in males.
Antibodies↗
Association of HLA-DR antigens with the development of cytotoxic antibodies in patients on dialysis.
Association between DR antigens and the occurrence of cytotoxic alloantibodies was studied in 251 patients on dialysis. Patients awaiting their first kidney graft were DR typed, and periodically investigated for the presence of alloantibodies. According to the observed peak panel reactive antibodies (PRA) the patients were divided into 3 groups: A, non-sensitized, B, moderately sensitized, and C, highly sensitized. The antigen DR3 was more frequent in sensitized (groups B + C) than in non-sensitized (group A) patients. This difference was significant on the level of P = 0.003, (Pcorr = 0.02). The antigen DR2 was more frequent in highly sensitized (group C) than in moderately sensitized (group B) patients with P = 0.002, not significant after correction for the number of investigated antigens.
Cytotoxicity, Immunologic↗
HLA antigens and the antibody response after vaccination to hepatitis B.
The aim of our work was the search for immunogenetic factors that influence the antibody response to HBs antigen. We analyzed the HLA-A, -B, and -DR antigen frequencies in 19 seropositive to HBs and 28 seronegative to HBs healthy persons finding an elevated frequency of B5 in the seropositive group (p value 0.037). After vaccination with Hevac B Pasteur vaccine of the seronegative persons, the low antibody response was associated with B13 (p value 0.041). An association between local side reactions to the vaccine and HLA A3 and B35 were also found (p values 0.042 and 0.022 respectively). The presented p values are not significant after correction for the number of antigens tested and for this reason our findings require confirmation in an independent study.
Adult↗
[Rejection of allogeneic bone marrow transplant. Case report].
In a patient aged 22 years with acute myeloblastic leukaemia during complete remission an allogenic transplant of bone marrow identical in the HLA antigen range was rejected despite administration before transplantation of a full marrow-ablating dose of busulphan (16 mg/kg) and severe graft-versus-host disease. Graft rejection manifested itself as disappearance of its haemopoietic function which was confirmed during the life and on autopsy. The case deserves attention in view of the rarity of HLA-identical marrow graft rejections in patients treated for leukaemias.
Adult↗
Tetra-t-butoxydisiloxane-1,3-diyl, a new type of bifunctional silyl protective group.
Tetra-t-butoxydisiloxane-1,3-diyl (TBDSi) group is introduced into nucleoside chemistry as an analogue of tetraisopropyldisiloxane-1,3-diyl (TIPDSi) and an example of a new type of bifunctional silyl protective group. Its introduction and properties of derivatives of ribonucleosides are presented.
Indicators and Reagents↗
HLA as an immunogenetic risk factor in juvenile chronic arthritis.
We investigated the frequencies of HLA-A, -B, -C and -DR antigens in diseased and control group with the aim to find immunogenetic factors that influence the pathogenesis and clinical course of juvenile chronic arthritis (JCA). The study was conducted on 73 JCA patients, 24 boys and 49 girls. On the basis of observed HLA antigen frequencies the relative risks (RR) and their statistical significance as well as the attributable risks (delta) were calculated. In the group of 73 JCA children the only statistically significant finding was a decreased RR for DR7. When the calculations were performed on boys taken from the JCA group, significantly higher RR were found for DR5, B27, B40 and A32. Further analysis was performed on clinically defined subgroups of JCA. In 15 children with pauciarticular persistent arthritis significantly increased RR and delta were found for A25, DR2 and DR3. No significant RR were observed in a subgroup of 44 sero-negative polyarticular arthritis. When only boys of this subgroup were selected for calculations, significantly increased frequencies were found for antigens A32, B40, DR1 and DR5. The reason for a stronger association of immunogenetic risk factors in diseased males than females is discussed.
Arthritis, Juvenile↗
HLA antigens and susceptibility to myasthenia gravis.
HLA-A, -B, -C and -DR antigen frequencies determined in a group of 73 myasthenia gravis (MG) patients were compared with those of a control group of 205 subjects. The strongest positive association with MG was found antigens B8 and DR3 (relative risks 9.56 and 8.84 respectively). Analysis of our data indicates that both antigens, independently from their linkage disequilibrium, are involved in susceptibility to MG. No relationship between HLA antigens on thymic pathology was observed in our material. In male MG patients the association with DR3 was weaker than in female patients. The difference in DR3 frequency between male and female patients was statistically significant; no significant difference was found for antigen B8. It appears that DR3 contributes to development of MG only in females. In male patients aged more than 30 years at the onset of disease, MG was not associated with B8 or DR3. In contrast, in female patients aged more than 30 years at the onset of disease there was a strong association of B8 and DR3 with the disease.
Adult↗