1/8. Girl with combined cellular immunodeficiency, pancytopenia, malformations, deletion 11q23.3 --> qter, and trisomy 8q24.3 --> qter.We describe here a 3-year-old girl demonstrating combined cellular immunodeficiency of B- and T-cells, pancytopenia, multiple anomalies, and severe mental retardation. cytogenetic analysis and fluorescent in situ hybridization (FISH) indicated an unbalanced translocation of chromosomes 8q and 11q, resulting in monosomy 11q23.3-qter and trisomy 8q24.3-qter. The association of cellular immunodeficiency and partial deletion 11q and/or partial trisomy 8q has not been described previously; however, the 11q deletion has been reported with humoral immunodeficiency or pancytopenia. Some one-third to one-half of patients with partial monosomy 11q were reported to have pancytopenia, which has been related to the absence of the 11q23-q24 region. Our case narrows down the critical interval for thrombo- or pancytopenia to 11q23.3-q24 and excludes both the ATM (which resides on 11q23.1) and the MLL genes as possible candidate genes. We are proposing that haploinsufficiency of the NFRKB gene on 11q24-q25 and/or the ETS-1 proto-oncogene on 11q24 may have caused or contributed to the immunodeficiency (decreased levels of B- and t-lymphocytes) in our patient.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. Multilineage hematopoietic engraftment after allogeneic peripheral blood stem cell transplantation without conditioning in SCID patients.Successful stem cell transplantation for patients with severe combined immunodeficiency (SCID) from matched family donors without conditioning results in engraftment of T lymphocytes. B lymphocytes engraft in only 50% of the cases, while myelopoiesis and erythropoiesis remain of host origin. Full hematopoietic engraftment was reported in one case after bone marrow transplantation without conditioning for a SCID patient. We studied three SCID patients who were transplanted with unmodified mobilized peripheral blood from HLA-identical family sex-mismatched members. They received megadoses of stem cells (18-23 x 10(6)CD34/kg). In contrast to the expected mixed chimerism that usually occurs in the absence of conditioning, we found in our patients 100% donor cell engraftment based on fluorescence in situ hybridization (FISH) and microsatellite techniques. Subset analysis of the engrafted cells using a multiparametric system enabling a combined analysis of morphology, immunophenotyping and FISH showed that both T and B lymphocytes and myeloid cells were of donor origin in two patients, while T lymphocytes and myeloid cells were of donor origin in the third. In the two cases with ABO incompatibility, erythroid engraftment was evidenced by blood group conversion from recipient to donor type. Multilineage donor engraftment is possible in SCID patients even without conditioning.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/8. Fatal B-cell lymphoproliferative syndrome in allogeneic marrow graft recipients. A clinical, immunobiological and pathological study.We have studied four cases of fatal B-cell lymphoproliferative syndrome (LPS) developing among 333 patients (incidence 1.2%) treated with allogeneic bone marrow transplantation (BMT). All four patients had received a T-cell depleted graft. Onset of the first clinical symptoms (palpable lymph node enlargement in three and IgA-lambda paraproteinemia in two patients) occurred between 41 and 188 days post-BMT (median 76 days). The course of the LPS was rapidly progressive in all cases, leading to death in 2-5 weeks. The peripheral blood showed progressive pancytopenia with disproportionally high numbers of activated NK cells, apparently compensating for the T-cell deficiency. Post-mortem histological studies disclosed polymorphic B-cell proliferations, most pronounced in the lymph nodes, spleen, liver, lungs and kidneys. Lymphohemopoietic cells were of donor origin in three patients. In the fourth patient, graft failure suggested a host origin for the proliferating cells. immunophenotyping and gene rearrangement analysis revealed polyclonal proliferation in one patient, monoclonal proliferation in another patient, and an oligoclonal pattern in the other two patients. The clinical behavior of the LPS was independent of clonality. Immunohistologically, the proliferating cells showed characteristics of relatively mature B-cells in three cases, and pre-B-cell features in one case. Epstein Barr virus (EBV) serology indicated seroconversion (primary infection) in one child, and chronic active EBV infection in both adults. EBV dna as well as EBV nuclear antigen (EBNA) were detected in infiltrated tissues of all four patients. The labeling pattern on in situ hybridization suggested a replicative EBV infection comparable to that in lymphoblastoid cell lines. We conclude that EBV-associated LPS developing as a result of post-transplant immunodeficiency is a distinct clinicopathologic entity, differing from non-Hodgkin's lymphoma (including Burkitt's lymphoma) and infectious mononucleosis of the immunocompetent host.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/8. The gene loci for immunoglobulin heavy chains in precursor B cell lines from a patient with severe combined immunodeficiency appear able to participate in dna rearrangement but have a germ-line configuration.In a previous study (immunogenetics 1988. 27:330) with Epstein-Barr virus, we established lines of precursor B cells from bone marrow cells of a patient with severe combined immunodeficiency in whom the numbers of B cells and T cells were markedly reduced. Although based on their surface markers these cell lines appeared to be at an early stage of B cell differentiation, the gene loci for immunoglobulin heavy chains (IgH) retained the germ-line configuration on both chromosomes in almost all the transformants. In this study, we found that the enhancer sequence, located between the JH and mu genes, was hypomethylated and an abundance of the germ-line Cmu transcript was detected in these cell lines by Northern hybridization. These results suggest that the chromatin structure of the IgH gene locus in these cell lines is accessible to VDJ recombinase and is able to participate fully in dna rearrangement. By contrast, we did not detect transcripts of the RAG-1 and RAG-2 genes, which are required for V(D)J recombination at gene loci for immunoglobulin and T cell receptors. Thus, it seems likely that these cell lines fail to initiate the V(D)J recombination process because of some deficiency in the formation of VDJ recombinase, which includes the inability to express RAG genes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/8. Multifocal remitting-relapsing cerebral demyelination twenty years following allogeneic bone marrow transplantation.We report a case study of a female who received an allogeneic bone marrow transplantation (BMT) from a sex-mismatched related donor and who, after a twenty-year interval, developed an acute fulminant biopsy-proven demyelinating disorder of cerebral white matter which followed a remitting-relapsing chronic course. in situ hybridization studies using Y-chromosome-specific markers revealed Y-chromosome-positive mononuclear cells in biopsy samples of white matter. magnetic resonance imaging (MRI) studies of the asymptomatic healthy male donor showed multiple white matter lesions. These observations suggest that donor lymphocytes were sensitized to central nervous system (CNS) antigens prior to or at the time of transplantation but remained dormant for 20 years before becoming activated to cause widespread demyelination.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/8. X-linked severe combined immunodeficiency with gamma delta T cells.A patient with X-linked severe combined immunodeficiency (X-SCID) was found to have a deletion mutation of a four base pair in the transmembrane domain of the IL-2 receptor gamma chain gene, a subunit shared by the receptors for IL-4, IL-7, IL-9, and IL-15 (common gamma chain; gamma c). He had very few alpha beta T cells but had a considerable number of gamma delta T cells in his peripheral blood. fluorescence in situ hybridization (FISH) analysis showed that the gamma delta T cells in his peripheral blood were not of maternal origin. He had received a bacillus Calmette-Guerin (BCG) vaccination before recognition of the disease, and the BCG infection remained quiescent with no reaction for 19 months. After successful bone marrow transplantation, the site of the BCG vaccination showed a reaction, and live BCG were detected. It is useful to consider the relationship between the existence of gamma delta T cells and BCG in this case, and it is suggested that gamma delta T cells may be, in a given situation, less dependent on the gamma c chain than are alpha beta T cells.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/8. Visible integration of the adenosine deaminase (ADA) gene into the recipient genome after gene therapy.Gene therapy for patients with adenosine deaminase (ADA) deficiency has become practical in the 1990s, and the exogenous gene has been reported to survive for several years in the recipient genome. To evaluate the integration efficiency of the ADA gene (ADA) into peripheral blood lymphocytes (PBL) of a patient with ADA deficiency who is receiving gene therapy, we performed two-color interphase fluorescence in situ hybridization (FISH) analysis by using digoxigenin-labeled ADA-cDNA and the biotin-labeled lambda-genomic ADA clone as probes. After each of 9 sequential series of gene therapy, interphase nuclei of 100 mononuclear cells from the patient were analyzed, and those of a LASN-producing cell line were used as a control. FISH signals were detected with rhodamine and FITC for the cDNA and the genomic dna, respectively. The number of PBL giving a transgene signal grew after the sequential gene therapies, and the proportion of signal-positive cells reached about 10%. Our results indicate that the two-color FISH system can be used as a potential aid to monitor the efficiency of the ADA gene therapy.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/8. Kabuki (Niikawa-Kuroki) syndrome associated with immunodeficiency.We report a case of a 19-year-old male with the cardinal features of the Kabuki syndrome (KS) and, in addition, with severe immunodeficiency. Finding immune deficiency in a KS patient, prompted us to determine whether this association was related to a deletion within the DiGeorge chromosomal region. fluorescence in situ hybridization (FISH) with the Oncor probe N25(D22S75) revealed no deletion of 22q11.2 in the patient.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |