[Severe combined immunodeficiency. Successful bone marrow transplantation from father to child].
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Adult↗
Biomedical subjects
T Plesner
Publications and source records attributed to T Plesner.
Demonstration of electrophoretic heterogeneity of serum beta 2-microglobulin in systemic lupus erythematosus and rheumatoid arthritis: evidence against autoantibodies to beta 2-microglobulin.
A sensitive crossed radioimmunoelectrophoretic method (CRIE), originally developed to study lymphocyte-associated beta 2-microglobulin (beta 2m), was applied in the study of serum beta 2m in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In six of seven patients with SLE and nineteen of twenty-seven patients with RA a considerable electrophoretic heterogeneity of serum beta 2m was found. In addition to the normally seen symmetric beta 2m precipitate, a beta 2m precipitate exhibiting complete immunochemical identity was found in the alpha-electrophoretic region. Binding of isolated 125I-labelled beta 2m to the abnormal precipitate was demonstrated in crossed immunoelectrophoresis. After gel filtration of sera exhibiting the above-mentioned beta 2m binding, all beta 2m was eluted in low molecular weight fractions corresponding to free beta 2m. By application of appropriate antisera and a glycoprotein-binding lectin in intermediate gels in CRIE, it was shown that the possible beta 2m-binding ligand is not an antibody, not a major constituent of normal human serum, and not unmodified HLA alloantigen. The abnormality was not restricted to patients with high disease activity but was found more frequently and was more pronounced (mean score 1.6 arbitrary units against 0.57 arbitrary units, P less than 0.01) in such patients. Thus our data exclude the possibility that autoantibodies to beta 2m were present in serum from patients with SLE and RA.
Antigen-Antibody Complex↗
Successful nonsibling bone marrow transplantation in severe combined immunodeficiency.
Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA-A antigen but was HLA-Dw2 homozygous like the patient; his lymphocytes showed a slight response to the patient's cells in mixed lymphocyte culture (MLC). At the age of 2 1/2 months and again at 5 months, she was given a bone marrow transplant from the father. During the entire course the patient had no infections, and apart from a transient eosinophilia she had no signs of graft-versus-host reaction. Immunological reconstitution was nearly complete at 9 months of age, when she was recontaminated. One year later plasma immunoglobulin concentrations are in the low normal range (IgG and IgM) or decreased (IgA); tests of cell-mediated immunity are normal. Apart from slight upper respiratory infections, the patient has been healthy. Physical and psychological development have been normal.
Bone Marrow Transplantation↗
Lymphocyte associated beta 2-microglobulin studied by crossed radioimmunoelectrophoresis.
A sensitive radioimmunoelectrophoretic assay was employed in the study of beta 2-microglobulin (beta2m) from human blood lymphocytes, allowing the detection of 2.5 pmol of beta2m corresponding to 3 x 10(6) lymphocytes. The intrinsic (amphiphilic) membrane proteins were solubilized and examined in crossed immunoelectrophoresis against rabbit antisera in the presence of non-ionic detergent. The beta2m associated precipitate was traced by post-electrophoretic incubation with 125I-labelled antibodies to beta2m and autoradiography. A polyspecific rabbit antiserum to human lymphoid cells retained its capacity to precipitate lymphocyte beta2m after absorption with isolated beta2m (on an immunosorbent column), showing that lymphocyte beta2m is complexed to other molecules. No free beta2m was found on lymphocytes when examined against the absorbed antiserum to human lymphoid cells in an intermediate gel and anti-beta2m in a reference gel.
Adult↗
Evidence for a change in the expression of beta2-microglobulin-assoicated membrane structures on leukaemic human cells.
Cell-associated and serum beta2-microglobulin was estimated in seven patients with chronic lymphocytic leukaemia. The amount of cell-associated beta2-microglobulin was significantly reduced (P less than 0.01), due to a decrease in the fraction of beta2-microglobulin that passes unretarded through a concanavalin A affinity column (presumably non-HLA-associated beta2-microglobulin). Serum concentrations of beta2-microglobulin were increased, but no correlation was found between the decrease in cell-associated beta2-microglobulin and the increase in serum beta2-microglobulin. All of the beta2-microglobulin from leukaemic serum was eluted corresponding to a molecular weight of 11,800 and none of it was retarded on a concanavalin A affinity column. The decrease in cell-associated beta2-microglobulin might reflect a change in the qualitative or quantitative expression of beta2-microglobulin-associated membrane structures on the leukaemic cells, perhaps conferring resistance to the cells against hypothetical immunological host defence mechanisms.
Beta-Globulins↗
Affinity chromatography of beta2-microglobulin from human lymphocytes on concanavalin-A-sepharose. Determination of carbohydrate-containing protein molecules complexed with beta2-microglobulin.
Beta2-microglobulin was extracted from human lymphocytes with nonionic detergent and separated by affinity chromatography on concanavalin-A-Sepharose. The retarded part of beta2-microglobulin is assumed to be associated with HLA antigens. Using a radioimmunoassay for beta2-microglobulin, the average number of presumably free beta2-microglobulin molecules and of presumably HLA-associated beta2-microglobulin molecules per lymphocyte was estimated to be 3.8 x 10(5) and 1.4 x 10(5), respectively.
Beta-Globulins↗
Neutrophil defect in multiple myeloma. Studies on intraneutrophilic lysozyme in multiple myeloma and malignant lymphoma.
Intracellular lysozyme concentration was measured in neutrophilic granulocytes from 25 patients with multiple myeloma. At diagnosis intraneutrophil lysozyme activity was significantly reduced (mean reduction 50%). During clinical remission after 1-4 months of intensive chemotherapy values were normalized. In 18 cases studied at various stages of the disease from 6 to 70 months after diagnosis there was a significant negative correlation between the duration of the disease and neutrophil lysozyme concentration. The decrease in neutrophil lysozyme concentration was significantly correlated to clinical disease activity and the percentage of plasma cells in bone marrow aspirates, whereas there was no correlation between the concentration of M-protein in serum and the neutrophil lysozyme concentration. Plasma lysozyme concentration was normal. In contrast, neutrophil lysozyme concentration was normal in 18 patients with stage III-IV malignant lymphoma. Plasma lysozyme in this group was significantly higher than normal. The difference in neutrophil lysozyme patterns between multiple myeloma and malignant lymphoma supports the hypothesis that the defect in neutrophil maturation seen in malignant blood disorders is directly related to the infiltration of the bone marrow by pathologic cells.
Antineoplastic Agents↗
Radioimmunoassay of beta2-microglobulin.
A radioimmunoassay for quantitation of beta2-microglobulin in serum and urine is described. Polyethylene glycol 6000 was used to precipitate the antigen-antibody complex. The assay can be performed within 5 hr. In healthy human subjects (mean age, 30.6 years and 42.0 years for serum and urine determinations, respectively) the mean concentration of beta2-microglobulin in serum was 125 nmol/l (range, 49-190 nmol/l). In men the mean 24-hr urinary excretion was 12.9 nmol (range, 8.6-19.2 nmol), and in women it was 5.5 nmol (range, 2.9-8.7 nmol). The assay range was 0.23-19.40 nmol/l, and the detection limit was 0.042 nmol/l, using a prolonged incubation time. The coefficient of variation based on 20 determinations in serum dilutions with a concentration of beta2-microglobulin of 8.14 and 1.92 nmol/l was 8.1 per cent and 9.0 per cent, respectively.
Adult↗
In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients.
Of 560 consecutive, newly diagnosed untreated patients with B CLL submitted for chromosome study, G-banded karyotypes could be obtained in 480 cases (86%). Of these, 345 (72%) had normal karyotypes and 135 (28%) had clonal chromosome abnormalities: trisomy 12 (+12) was found in 40 cases, 20 as +12 alone (+12single), 20 as +12 with additional abnormalities (+12complex). Other frequent findings included abnormalities of 14q, chromosome 17, 13q and 6q. The immunophenotype was typical for CLL in 358 patients (CD5+, Slg(weak), mainly FMC7-) and atypical for CLL in 122 patients (25%) (CD5-, or Slg(strong) or FMC7+). Chromosome abnormalities were found significantly more often in patients with atypical (48%) than in patients with typical CLL phenotype (22%) (P < 0.00005). Also +12complex, 14q+, del6q, and abnormalities of chromosome 17 were significantly more frequent in patients with atypical CLL phenotype, whereas +12single was found equally often in patients with typical and atypical CLL phenotype. The cytomorphology of most of the +12 patients was that of classical CLL irrespective of phenotype. In univariate survival analysis the following cytogenetic findings were significantly correlated to a poor prognosis: chromosome 17 abnormalities, 14q+, an abnormal karyotype, +12complex, more than one cytogenetic event, and the relative number of abnormal mitoses. In multivariate survival analysis chromosome 17 abnormalities were the only cytogenetic findings with independent prognostic value irrespective of immunophenotype. We conclude that in patients with typical CLL immunophenotype, chromosome abnormalities are somewhat less frequent at the time of diagnosis than hitherto believed. +12single is compatible with classical CLL, and has no prognostic influence whereas chromosome 17 abnormalities signify a poor prognosis. In patients with an atypical CLL immunophenotype, chromosome abnormalities including +12complex, 14q+, del 6q and chromosome 17 are found in about 50% of the patients, and in particular chromosome 17 abnormalities suggest a poor prognosis.
Aged↗
Subcellular distribution of urokinase and urokinase receptor in human neutrophils determined by immunoelectron microscopy.
A high-affinity receptor for urokinase-type plasminogen activator (uPAR) has been identified on the plasma membrane of a number of different cell types, and has been shown to be important for plasminogen activation, cell adhesion, and possibly signal transduction. uPAR and uPA cosediment with secretory vesicles and specific granules by subcellular fractionation and translocate to the plasma membrane upon activation of neutrophils. Here the subcellular distribution of uPAR and uPA is studied by electron microscopy of neutrophils using immunogold double labeling for uPAR and uPA and a set of markers for well-defined subtypes of granules: matrix metalloproteinase type-9 (MMP-9) for gelatinase granules, lactoferrin (LF) for specific granules, and myeloperoxidase (MPO) and neutrophil elastase (NE) for primary granules. With this technique uPAR colocalizes with uPA in 71% of labeled granules. In granules containing uPAR the degree of coexpression with MMP-9, MPO and NE was 19, 66, and 74%, respectively. In granules labeled for uPA the corresponding overlap with MMP-9, MPO and NE was 24, 64, and 51%, respectively. Low levels of co-localization were found for uPAR and LF (7%) and for uPA and lactoferrin (5%). The results indicate that uPAR and uPA are present in gelatinase granules and primary granules, but rarely in specific granules. The demonstration of uPAR and uPA in primary granules is of particular interest, and may indicate that uPAR and uPA participate in the activation of latent hepatocyte growth factor of neutrophils.
Biomarkers↗