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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe immunodeficiency is associated with reactivation of latent Epstein-Barr virus (EBV) that is manifested by virus replication. It is unknown whether EBV replication also occurs in the Hodgkin's disease (HD) tissue of patients infected with the human immunodeficiency virus (HIV). Therefore, we studied paraffin-embedded lymph nodes from 13 cases of HIV-associated HD to determine the latent or replicative state of EBV infection. All patients were seropositive HIV-infected men; additional clinical information was available for 12 patients. The risk factor(s) for HIV infection were homosexuality (n = 7), intravenous drug abuse (n = 2), homosexuality and intravenous drug abuse (n = 1), sexual promiscuity (n = 1), or hemophilia (n = 1). Advanced clinical stage and B symptoms were common at the time of initial diagnosis of HD. The histological subtype of Hodgkin's disease was universally mixed cellularity, except for a single case classified as nodular sclerosis. Seven cases exhibited foci of relative lymphoid depletion. Five cases contained foci of necrosis. Reed-Sternberg (RS) cells and RS cell variants were positive for CD30/BerH2 and negative for CD45/LCA, CD45RO/UCHL1, and CD20/L26 in all cases. Tumor cells were positive for CD15/LeuM1 in seven cases. In all 13 cases, RS cells and RS cell variants were infected by latent EBV as shown by in situ hybridization to EBV-encoded ribonucleic acid (EBER1). In 12 of 13 cases neoplastic cells coexpressed EBV latent membrane protein 1 (LMP1). EBV replication was examined by two different methods: immunohistochemistry to identify EBV-encoded BZLF1 protein and in situ hybridization to detect EBV BHLF1 transcripts. No positivity in RS or RS cell variants was detected with either assay of EBV replication (95% confidence interval [CI] = 0% to 23%). The findings confirm that EBV is detected more frequently in HIV-associated HD when compared with immunocompetent patients with HD. The findings also suggest that EBV is tightly latent within RS and RS cell variants of HIV-associated HD. It appears that factors other than host immune status are important in maintaining EBV latency in HIV-associated HD.
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PMID:Human immunodeficiency virus-associated Hodgkin's disease contains latent, not replicative, Epstein-Barr virus. 881 1

A case of fatal Epstein-Barr virus (EBV) associated lymphoproliferative disorder is reported in an 11 month old female. Heavy infiltrates of CD20 + and EBV EBER mRNA expressing lymphoid blasts were found to cause a series of ulcers along the entire length of the gastrointestinal tract and there was an ileal perforation. Similar infiltrates were also found in lymph nodes, spleen, and liver. Although blood phenotypic analysis performed shortly before her death revealed a severe decrease in T lymphocytes, neither the patient nor other members of her family had a history of primary or secondary immunodeficiency. EBV infection is common in children. However, such a fatal infection of the virus has not apparently been described previously in infants without pre-established immunodeficiency.
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PMID:Epstein-Barr virus associated lymphoproliferative disorder with fatal involvement of the gastrointestinal tract in an infant. 761 66

Bone marrow transplantation is characterized by a prolonged period of humoral immunodeficiency in which many patients have abnormal circulating B-cell subsets, and oligoclonal and monoclonal gammapathies. In this study we examine B-cell precursor reconstitution in the post-transplantation marrow. Within 1 month after transplantation there is a marked increase in the percentage of immature B cells (to 80% of marrow lymphocytes), which can persist for more than 1 year. The increase in B-cell precursors is seen in both adults and children and appears to be independent of age. These cells have a normal precursor B-cell surface antigenic phenotype (CD19+, CD10+, CD20 negative to dim) and generally express very little CD34. No monoclonal or oligoclonal immunoglobulin gene rearrangements are detected in these cells, which enables them to be easily distinguishable from common precursor B-cell acute lymphocytic leukemia lymphoblasts.
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PMID:B-cell precursor bone marrow reconstitution after bone marrow transplantation. 804 94

We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.
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PMID:Characterization of a new IL-6-dependent human B-lymphoma cell line in long term culture. 814 4

High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma.
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PMID:Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. 820 68

The 50% macaque infectious dose (MID50) and pathogenesis of uncloned simian immunodeficiency virus (isolated from a pigtailed macaque, SIVmne) was determined in longtailed macaques (Macaca fascicularis). Five pairs of macaques were inoculated with 10-fold dilutions of the virus stock, and one macaque was mock-infected. The virologic and clinical status of these macaques was monitored for up to 80 weeks. The MID50 of SIVmne was determined to be 10(2) cell culture infectious dose of the original virus stock. In order to test the infectivity and pathogenesis of an established viral dose, six additional macaques were inoculated with 10x MID50 (10(3) cell culture infectious dose) of the SIVmne. The virologic and clinical status of these macaques was monitored for 40 weeks. All of the macaques inoculated with 10x MID50 or greater became infected as evidenced by seroconversion and consistent virus isolation from peripheral blood mononuclear cells. Macaques infected with SIVmne had an initial sharp decrease in CD2, CD20, CD4, CD8, and CD4CD29 lymphocyte subsets, whereas the CD4:CD8 ratio increased. Viremic macaques developed persistent slight to moderate peripheral lymphadenopathy approximately 3 to 4 weeks after inoculation. Four macaques subsequently died of AIDS-like disease at 29, 33, 42, and 80 weeks after inoculation. Data obtained from the viral titration study and the acute infection model will aid in the development of animal trials to evaluate antiretroviral therapies and preventive vaccines against human immunodeficiency virus infection.
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PMID:Infectivity and pathogenesis of titered dosages of simian immunodeficiency virus experimentally inoculated into longtailed macaques (Macaca fascicularis). 827 18

We have previously shown that retinoids can induce differentiation of B cells in vitro as well as in vivo in patients with common variable immunodeficiency (CVI). While changes were observed over 1 week when retinoic acid (RA) was added to CVI hybridoma cells in vitro, maturation of the patients' B-cell compartment in vivo occurred only after 4 months of drug administration. We have now performed a 64-week open trial of oral 13-cis RA in five patients to see if prolonged treatment would result in continued improvement in their humoral immune compartment. In this trial, drug was given for 32 weeks followed by a 32-week wash-out period. During the treatment, the patients showed changes in a variety of parameters indicating an alteration towards normal of their humoral immune systems. This change included a fall in the elevated circulating interleukin-6 (IL-6) levels, a more normal display of B-cell surface markers (L-selectin and CD20), a decrease in B-cell size, and improved in vitro and in vivo B-cell function. In order to determine if VH gene use was affected by the retinoid treatment, VH gene expression in the CVI patients was characterized. Results showed an unusual predominance of non-mutated VH gene sequences, representative of cells that are recent bone marrow emigrants. While no common pattern of change occurred in VH gene segment use in the patients while on retinoid therapy, large-scale (> 10-fold) changes in the expression of these genes were observed in each individual over time. Taken together, these results provide multiple lines of evidence that 13-cis RA promotes maturation of B cells in patients with CVI. However, the effect appears to be partial, such that stimuli in addition to 13-cis RA will be necessary to provide for further B-cell differentiation in order to achieve normalization of humoral immunity.
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PMID:Long-term administration of 13-cis retinoic acid in common variable immunodeficiency: circulating interleukin-6 levels, B-cell surface molecule display, and in vitro and in vivo B-cell antibody production. 828 20

From September 1984 through December 1991, of those with human immunodeficiency virus infection seen at the acquired immune deficiency syndrome unit of the Centro di Riferimento Oncologico, Aviano, Italy, 71 patients had systemic non-Hodgkin's lymphomas. The most frequent histotypes were small noncleaved cell, anaplastic large cell (ALC) CD30/BerH2+, and large cell immunoblastic. In 22 representative cases of these histotypes, including 9 of small noncleaved cell, 9 of ALC CD30/BerH2+, and 4 of immunoblastic non-Hodgkin's lymphomas, Epstein-Barr virus genetic information was assessed by in situ hybridization and correlated with histologic and immunophenotypic findings. Expression of B-cell associated markers, usually including CD19, CD20, CD22, CDw75, and CD74, was found in 17 of the 22 evaluated cases. All small noncleaved cell and immunoblastic cases and four cases of ALC lymphomas expressed B-cell immunophenotypes, whereas the remaining ALC cases were immunologically undetermined. In situ hybridization detected Epstein-Barr virus in 12 of 22 cases (54.5%). Seven of nine ALC lymphomas were positive, as were three of five small noncleaved cell type (Burkitt's lymphoma), one of four small noncleaved cell type (non-Burkitt's variant), and one of four large cell immunoblastic type. The results of this study indicate that Epstein-Barr virus genomes might be identified in more than 50% of the evaluated high grade non-Hodgkin's lymphomas; this association occurred significantly more often in the small noncleaved cell lymphomas resembling endemic Burkitt's lymphoma (60%) and with ALC CD30/BerH2+ lymphomas (77.8%). These findings support the notion that Epstein-Barr virus may play a role in the development of non-Hodgkin's lymphomas in a proportion of human immunodeficiency virus-infected patients.
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PMID:Demonstration of Epstein-Barr viral genomes by in situ hybridization in acquired immune deficiency syndrome-related high grade and anaplastic large cell CD30+ lymphomas. 838 22

The Epstein-Barr virus (EBV) has been implicated in the pathogenesis of Hodgkin's disease, with an frequency of 15 to 50% in the immunocompetent host. We studied 12 formalin-fixed, paraffin-embedded cases of Hodgkin's disease occurring in human immunodeficiency virus-infected individuals to determine the frequency of EBV in Hodgkin's disease from this population. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated anti-sense oligonucleotide complementary to the EBER1 gene of EBV. EBV RNA was found in the Reed-Sternberg cells and variants in 11 of 12 cases. Double-labeling studies confirmed the presence of EBV RNA in CD15-expressing Hodgkin's cells in all 11 cases, although rare B lymphocytes coexpressing EBV RNA and CD20 were also noted in these cases. The Hodgkin's cells in all 11 EBER-positive cases expressed latent membrane protein. The one case negative for EBV RNA showed the histology of nodular, lymphocyte predominance, a subtype thought to be distinct from other types of Hodgkin's disease.
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PMID:High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of HIV-associated Hodgkin's disease. 838 41

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage-specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty-two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in four of five cases studied. All nine cases were of T- or null-cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus-positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.
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PMID:CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease. 863 11


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