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Biomedical subjects

H Grosse-Wilde

Publications and source records attributed to H Grosse-Wilde.

At least 91 records · Page 5Linked to original sources
PubMed1994

T lymphocyte recognition sites on peripheral nerve myelin P0 protein.

Synthetic peptides corresponding to the extracellular and cytoplasmic domain of bovine (b) or rat (r) peripheral myelin P0 protein were used to establish a total of 50 short-term T cell lines (TCL) from blood of eight healthy subjects. Despite expressing different HLA-DR and HLA-DQ specificities, one or more TCL (range 1-16) specific for peptide bovine P0 19-38 could be isolated from the blood of each donor. Therefore, this peptide covers an immunodominant T cell recognition site in humans. However, when testing seven bP0-19-38-specific TCL derived from blood of two healthy subjects for recognition of the corresponding human P0 sequence, no TCL showed any proliferative response. Bovine P0-19-38 differs in only two amino acid residues from the human peptide. This observation stresses the necessity for using homologous antigens when screening for T cell-mediated autoreactivity to myelin antigens in humans. Unexpectedly, we failed to establish a single P0 peptide-specific TCL from blood of four patients with acute Guillain-Barré syndrome (GBS), in which P0 is considered a putative target autoantigen. As already suggested by others, this could indicate that T cell responses to P0 do not play a pathogenic role in all GBS cases. Alternatively, in these four patients neuritogenic P0-specific T lymphocytes may have been sequestrated to peripheral nerves.

Adult↗
PubMed1994

Segregation study of the soluble 39-kD HLA class I heavy chain.

To study the variable expression and inheritance of the 39-kD M(r) form of HLA class I molecules, we investigated the plasma of 12 families with 61 members and 41 unrelated individuals by SDS gel electrophoresis and class-I-specific immunoblotting. Seven families were informative for the presence and absence of the 39-kD band with a clear segregation pattern in coupling with HLA. The data were in agreement with a codominant expression of this molecular variant of sHLA class I. Of the 48 independent HLA haplotypes, 19 were identified as carrying the 39-kD deficiency. However, there was no clear association with HLA-B7 or gender. Under the assumption that all haplotypes in the five non-informative families carried the expressed 39-kD variant, approximately 40% of the Caucasian population should be heterozygous deficient for the 39-kD band of sHLA class I.

Antibodies, Monoclonal↗
PubMed1994

Soluble HLA class I and beta-2-microglobulin plasma concentrations during interferon treatment of chronic myelogenous leukemia.

Soluble class I molecules (sHLA-ABC) were measured by an enzyme-linked immunosorbent assay (ELISA) in plasma samples of 13 patients with chronic-phase Ph1-positive chronic myelogenous leukemia (CML). The patients were treated once daily with interferon (IFN) s.c. at a dosage of 4 x 10(6) IU/m2 IFN-alpha-2b or in combination with 50 micrograms IFN-gamma. Measurements were performed before 2, 4, 6, 8, 24, 48, and 72 h after the start of treatment and thereafter every 2-4 weeks. Baseline sHLA-ABC levels were within normal limits (mean 22.1 +/- 8.8 mg/l). An initial decrease of sHLA-ABC (mean 3.2 +/- 2.7 mg/l) was seen in all patients during the first 2-8 h of IFN treatment. Thereafter, sHLA-ABC levels increased steadily reaching maximum values within 2-5 weeks. The overall increase was 12.7 +/- 12.4 mg/l. During the following 2-4 months of IFN treatment sHLA-ABC decreased to near baseline levels in 12 of 13 patients. No difference was detected between IFN-alpha and IFN-alpha plus IFN-gamma treatment. beta 2-Microglobulin values were measured in 8 patients and were found to be correlated to sHLA-ABC concentrations (r = 0.48).

Adult↗
PubMed1994

Detection efficacy of soluble HLA-A, B antigens using 1D-IEF.

Soluble HLA class I alloantigens (sHLA class I) can be typed according to their isoelectric points (IEP) after immunoprecipitation by w6/32 monoclonal antibody (mAb) coupled to immunomagnetic beads and focusing. In order to prove the large scale efficacy of this methodology, EDTA-plasma samples from 344 probands HLA-A, B typed by serology were analysed by one-dimensional isoelectric focusing and HLA class I specific Westernblot (1D-IEF). In addition, detergent solubilized HLA class I membrane molecules from approximately one half of the probands were studied too. Soluble HLA-A24,B7,B18,B62 antigens were identified in nearly all experiments, whereas A28, B13, and B51 could be detected in about 50%. A third group of HLA antigens (A26, B8, B44) could be visualized rarely. The difficulties of detection might be due to the different affinity of mAb w6/32 to certain sHLA class I gene products or to variable amounts of sHLA class I in the plasma specimens. Some modifications of the antigen capture technique have already led to a slightly better degree of antigen recognition in 25 probands tested. Thus, HLA-A, B typing using sHLA molecules and 1D-IEF in the assay format presented does not yet seem to be a definitive alternative for HLA class I serology or biochemistry of membrane-bound HLA class I molecules but it should be a promising technique if no cells are available or donor-derived sHLA allotypes are to be monitored after HLA mismatched organ transplantation.

Antibodies, Monoclonal↗
PubMed1994

Immunogenetic marrow donor search for 1012 patients: a retrospective analysis of strategies, outcome and costs.

To analyse strategies, outcome and costs of immunogenetic marrow donor search 1012 patients were enrolled in a retrospective single centre study covering the period from January 1990 to December 1992. An HLA-compatible donor was identified for 562 of the patients (55.4%). Core family donor search (CFDS) provided a donor for 39%, extended family donor search (EFDS) for 6.4% and unrelated marrow donor search (UMDS) for 10% of the patients. During the period analysed, UMDS success rate increased from 13.3% to 47.8%, while mean search length decreased from 7.2 to 4.8 months. The percentage of donors from German registries rose from 5% in 1990 to 50% in 1993. Search length was dependent on patient's HLA phenotype frequency, but even for patients with frequencies as low as < 1:3 000 000 a donor was found in 5 of 24 cases. The mean costs (DM) per donor identified by CFDS, EFDS and UMDS were 2921, 19 172 and 24 036, respectively. Thus, CFDS is the utmost effective type of search. In view of the clinical outcome of BMT, EFDS remains a meaningful strategy and should not be replaced by UMDS despite its increasing success rate.

Actuarial Analysis↗
PubMed1994

Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell origin.

The carcinoembryonic antigen (CEA) and the classical non-specific cross-reacting antigens (NCAs) belong to the CEA gene family which is part of the immunoglobulin superfamily. In normal hematopoiesis, CEA gene family members (CGMs) have only been reported on cells of myeloid and monocytic origin. In the present study, we analyzed 62 childhood acute lymphoblastic leukemias (ALLs) and seven surface immunoglobulin positive (sig+) B-cell lines for the expression of the CEA family members CEA, NCA-50/90, NCA-95, NCA-160, CGM1 and CGM7. We demonstrated that members of the CEA family were present in 76% of childhood ALLs of B- and T-cell origin. In ALLs of B-cell origin, 82% of the samples expressed at least one CEA subgroup member: 38% NCA-50/90 (CD66c), 31% NCA-160 (CD66a), and 13% both. Six of seven B-cell lines solely expressed NCA-160. In seven ALL of T-cell origin, sole NCA-160 expression was present in 29% of the cases. CEA and CGM1 were not expressed in childhood ALLs or in the sIg+ B-cell lines. In 15 ALLs and seven B-cell lines which could be analyzed for CGM7 expression, the antigen was not detected. NCA-95 was not expressed in 91% of the B-lineage ALLs, in T-lineage ALLs and in the B-cell lines. However, five B-lineage ALLs showed conflicting data on the binding patterns of two, on leukocytes specifically NCA-95 recognizing antibodies suggesting either expression of unknown forms of NCA-95 or NCA-50/90 or of a yet unknown member of the CEA family in these ALL cells. The expression of CEA subgroup members in childhood ALL cells might have prognostic impacts, as an inverse correlation exists between NCA expression on leukemic blasts and the risk factor white blood count at diagnosis.

Adolescent↗
PubMed1993

Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow transplantation.

Insulin-dependent diabetes was observed in a woman, aged 29, 4 years after transplantation of bone marrow from her HLA-identical brother with insulin-dependent diabetes. Both had classic symptoms and insulin dependency from onset. At diagnosis of diabetes the recipient was positive for high-titre islet cell antibodies (ICA) whereas she had been ICA negative before transplantation. Chromosomal analyses verified that all circulating leucocytes were of male donor type. These findings suggest transfer of insulin-dependent diabetes by bone marrow cells and confirm the immune nature of the disease.

Adult↗
PubMed1993

Soluble CD4, CD8, and HLA molecules in commercial immunoglobulin preparations.

CD4 and CD8 exist in membrane-bound and soluble forms. These antigens are the physiological ligands for molecules of HLA classes I and II, which we have found in soluble form in commercial immunoglobulin preparations. We measured concentrations of soluble CD4 and CD8, as well as soluble HLA-ABC and HLA-RQP in sixteen immunoglobulin preparations by enzyme immunosorbent assays. Only two preparations contained detectable CD8, and nine had soluble CD4 in varying amounts. There was great variation in concentrations of soluble HLA molecules. It is possible that the immunomodulating effects of immunoglobulin therapy in disorders with immune aetiology are due, at least partly, to these contaminating molecules.

CD4 Antigens↗
PubMed1993

Impaired antigen-presenting capability of monocytes correlated with their decreased expression of HLA-II antigens in patients with myeloid leukemia.

Antigen-presenting capability and expression of HLA-II antigens on peripheral blood monocytes were analyzed by isotope incorporation technique and indirect immunofluorescence assay with monoclonal antibodies Tü 22, Tü 36 and anti-Leu-M2 in patients with acute and chronic myeloid leukemias (AML, CML). All patients (17 AML and 13 CML) demonstrated impaired antigen-presenting capability of monocytes (P < 0.001), when compared with simultaneously studied controls, which were HLA-identical normal siblings of the patients. These patients also showed a markedly decreased proportion of MAC-120- and HLA-DQ-positive monocytes as compared with the controls (P < 0.001), while the percentage of HLA-DR-positive monocytes in the patients was similar to that observed in the controls (P > 0.05). These findings suggested, therefore, that impaired antigen-presenting capability of monocytes correlated with their decreased expression of HLA-DQ in patients with acute and chronic myeloid leukemias.

Adolescent↗
PubMed1993

Summary report from the first international workshop on soluble HLA antigens. Paris, August 1992.

The First International Workshop on Soluble HLA antigens focused on the comparison of immunoassay procedures for quantitation of soluble HLA (sHLA) class I antigens and the selection of a sHLA class I antigen international standard. Several sets of serum, plasma, and cell culture supernatant specimens were assayed blindly for levels of sHLA class I antigens by 15 participating laboratories using different immunoassay formats. The sandwich ELISA using (i) for antigen capture: an anti-HLA class I heavy chain monoclonal antibody (mAb) specific for a monomorphic epitope, and (ii) for antigen detection: an anti-beta 2 microglobulin antibody-enzyme conjugate, was the assay format of choice. There was a high inter-laboratory correlation among the majority of laboratories. All serum and plasma specimens from normal donors, and from a single transplant patient, had detectable levels of sHLA class I antigens. Paired serum and plasma specimens had similar levels of sHLA class I antigens, although plasma sHLA antigens seemed more stable than serum sHLA antigens. sHLA-A2 and sHLA-B7 antigens were detected in all specimens from HLA-A2 and HLA-B7 donors, respectively, using allele-specific ELISAs. No difference in reactivity was observed for quantitation of native sHLA class I antigens whether the capture mAb was TP25.99 (alpha 3 domain-specific) or W6/32 (alpha 2 + alpha 3-specific). However, a human-mouse chimeric sHLA class I antigen reacted weakly in assays which used TP25.99 mAb. The wide variation among laboratories in their reporting of micrograms/ml units pointed to the need for an inter-laboratory standardization based on a calibrated sHLA antigen preparation. T.sB7, an sHLA-B7 antigen derived from a cell line transfected within human beta 2 microglobulin and HLA-B7 genes, was accepted as the First sHLA class I Antigen International Standard at the workshop meeting.

Alleles↗
PubMed1993

Measles virus-directed responses of CD4+ T lymphocytes in MS patients and healthy individuals.

To analyze the antigen specificities of measles virus (MV)-reactive CD4+ T cells in multiple sclerosis (MS) patients as compared with those of healthy donors, we established 492 MV-reactive short-term T-cell lines (TCL) from blood of 12 MS patients (n = 243 TCL) and 12 healthy subjects (n = 249 TCL). We determined antigen specificities of these TCL by proliferative responses to optimal concentrations of recombinant MV structural proteins (MV-SP) and human myelin basic protein (MBP). In both donor groups, there was a dominant reactivity against the MV fusion protein and the MV nucleocapsid protein. However, there was a substantial heterogeneity of T-cellular polypeptide specificities among MS patients as well as among healthy individuals, which was true even in subjects sharing identical HLA-DR and HLA-DQ haplotypes. By comparing the T-cell antigen specificity patterns obtained in both donor populations, we found decreased percentages of TCL reactive with the MV fusion protein, the hemagglutinin, and the phosphoprotein in MS patients, but these differences failed to reach statistical significance. None of the 492 MV-specific TCL, nor an additional 276 TCL, showed any reactivity to MBP. Therefore, we did not detect any MS-specific pattern of T-cell responses to MV-SP. Furthermore, our study suggests that mechanisms other than molecular mimicry between MV-SP and MBP may cause myelin-directed autoimmunity.

Adult↗
PubMed1993

Rapid detection of engraftment using T cell receptor gene polymorphism after allogeneic bone marrow transplantation in an alloimmunized child with severe aplastic anemia.

A severely alloimmunized boy with aplastic anemia received an HLA-identical BMT from his brother. Despite intensive immunosuppression and large marrow dose, peripheral signs of engraftment occurred only late under G-CSF treatment. With leukocyte counts of < 0.5 x 10(9)/l, chimerism could be proven not only by oligonucleotide fingerprinting but also within 48 h by analysis of polymorphism in the TCR gene family. This rapid and sensitive method to detect engraftment before it became quantitatively evident was important for the clinical management of the patient, obviating the need to search for an alternative marrow donor.

Anemia, Aplastic↗
PubMed1992

Molecular detection of genetic defects in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a study of 27 families.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) deficiency is inherited as an autosomal recessive trait. Patients can present with the salt wasting, simple virilizing or a non-classical form of the disease. The gene for P450C21, the enzyme carrying 21-OHase activity, has been mapped to the major histocompatibility complex on chromosome 6p. Using molecular hybridisation techniques we have studied the genetic defect in 27 families with one or more affected offspring diagnosed and treated at the University Hospital of Essen. DNA samples were digested with restriction endonuclease TaqI, PvuII, BglII, and EcoRI and analysed by Southern blot hybridisation with the cDNA probe pC21/3c. Eleven of 40 haplotypes associated with the salt wasting form were found to have a large deletion of 30 kb affecting the 5' end of the active 21-OHase gene and the 3' end of the closely linked pseudogene. Results in another 11 cases are compatible with gene conversion; 18 cases were not informative. The 30 kb deletion was associated with a combination of the HLA antigens Bw47 and DR7 in 7 of 11 cases. In the haplotypes with gene conversion, no linkage disequilibrium to HLA antigens was found. No apparent gene alterations were detected in simple virilizing and non-classical haplotypes. The direct detection of the genetic defect in 55% of the salt wasting haplotypes may help to improve predictive testing in families with CAH.

Adrenal Hyperplasia, Congenital↗
PubMed1992

Soluble HLA class I and class II concentrations in commercial immunoglobulin preparations.

Soluble HLA class I (sHLA-ABC) and class II (sHLA-RQP) molecules were quantitated in 16 commercially available immunoglobulin (Ig) preparations by enzyme-linked immunosorbent assays. Whereas three Ig preparations contained no detectable sHLA-ABC, all preparations showed concomitant sHLA-RQP molecules. There was a considerable variability with regard to the individual sHLA concentrations. For sHLA-RQP the values exceeded that found in human plasma of healthy individuals, suggesting that the extraction procedure may concentrate not only Ig, but also HLA class II molecules. Based on the total dosage of intravenously administered immunoglobulins (i.v.Ig), contaminating sHLA molecules may become immunogenic. Furthermore, sHLA molecules are discussed in terms of participation in the well-known immunomodulating effects of i.v.Ig therapy.

Enzyme-Linked Immunosorbent Assay↗