Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phenotypic analysis of human umbilical cord blood (CB) mononuclear cells is important to study their maturity and differentiation regarding their transplantable capacity. In this work we have studied differential expression of B cell antigens on CD5-/HLA-DR+ B cells (B1b, B2) and CD5+/HLA-DR+ cells (Bla) from the CB (n=6) and adult peripheral blood (PB) (N=6). CD5-PE, HLA-DR-PerCP and FITC labelled anti-B cell MoAb panel of the 6th International Workshop on Human Differentiation Antigens were used for detection of B cell subpopulations. FacsCalibur (B-D) flow cytometer was used for evaluation of samples. CB Bla (CD5/HLA-DR++) cells proved to be positive with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD76, CD79, MHC-II, IgM and anti Ig light chains MoAbs. CB B1b (CD5-/HLA-DR+) cells reacted with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD79, MHC-II, and IgM MoAbs. PB B cells (B2) expressed CD19, CD20, CD21, CD22, CD24, CD32, CD37, CD39, MHC-II and CD79 Ags. Unlike to the PB the CB B lymphocytes proved to be predominantly B1 cells representing a new-born B cell repertoire. Besides expressing many B cell antigens both the CB Bla and B1b cells showed CD9+, CD45RA+, IgM+ immature, "naive" B cell phenotype. Functionally, B1 cells are capable producing polyreactive IgM and natural autoantibodies but not IgG. This antibody profile might be insufficient regarding the recipient humoral immune defense result in more severe immunodeficiency after CB transplantation.
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PMID:Immunophenotypic characterisation of cord blood B-lymphocytes. 991 47

Skin biopsy sections of Kaposi's sarcoma (KS) from 25 patients (5 AIDS-related, 20 classical cases) were histologically staged and hybridized in situ with oligonucleotide probes for constitutively transcribed human herpesvirus 8 (HHV-8) mRNA T0.7 and T1.1 using a colourimetric technique. T1.1 increases during experimental induction of the viral lytic phase in the HHV-8-infected lymphocytes of primary effusion lymphoma and its colourimetric detection in KS cells presumably corresponds to virion production. Immunostaining with anti-CD20, CD45RO, MAC 387, and alpha-smooth muscle actin was performed following T1.1 in situ hybridization (ISH). When the amount of T0.7 was above the detection threshold, the signal was made up of multiple coarse intranuclear dots in most spindle cells. Of the six early-stage lesions, none produced a T1.1 hybridization signal. Two of four AIDS-related and two of eight classical lesions with incipient spindle cell growth produced rare but distinct dense intranuclear T1.1 signals in endothelial cells lining narrow tubes. In contrast, eight of ten (all classical KS) mature spindle cell lesions displayed a signal, scattered in up to 2 per cent of spindled endothelial cells. Cell types other than endothelium produced no T1.1 hybridization signal in double stains. The results are consistent with other published data indicating latent HHV-8 infection in endothelium and its tumour cell progeny, with simultaneous virion production in a small subset of cells. Immunodeficiency may not influence the number of cells lytically infected with HHV-8 in early KS, in contradistinction to other herpesviruses with latent-lytic cycles.
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PMID:Dominant human herpesvirus type 8 RNA transcripts in classical and AIDS-related Kaposi's sarcoma. 1039 25

Few reports on syphilitic lymphadenopathy have appeared in 20 years, and none have compared findings in patients with and without human immunodeficiency virus (HIV) infection, despite the recent epidemic spread of syphilis and HIV. Twelve cases of syphilitic lymphadenopathy were studied and grouped according to HIV status. Patients were 21 to 62 years old (median, 29 years); 7 were men, 5 were women. Biopsy sites were cervical (7 cases), inguinal (4), and axillary (1) lymph nodes. All patients had evidence of syphilis. Rapid plasma reagin titers ranged from 1:32 to 1:512. Treponemal hemagglutination was positive in all cases tested. Spirochetes were found with Steiner staining in 2 cases. HIV testing was positive in 4, negative in 2, and unknown in 6 cases. Lymph nodes were enlarged and often fragmented due to capsular fibrosis and chronic inflammation, with focal obliteration of the subcapsular sinus. Follicular and interfollicular hyperplasia was seen in all cases and was usually marked, with prominent vascular proliferation, plasma cells, immuno-blasts, histiocytes, and occasional neutrophils. Follicle lysis and granulomas suggestive of unconfirmed toxoplasmosis were each seen in 1 case, and Kaposi sarcoma in 2, all in HIV-positive patients. Lymphoplasmacytic infiltration was marked, especially in interfollicular areas, with peri-vascular plasma cell cuffing in all cases and obliterative endarteritis in about half (7 of 12, 56%). Immunostaining for CD45RO (UCHL-1), CD20 (L26), kappa, lambda, and CD68 (Kp-1) revealed a mixed population of T cells, polyclonal B cells, and interfollicular histiocytes. Distribution of T and B cells (immunoarchitecture) was essentially normal and similar in all cases, regardless of HIV status. Syphilis produces essentially identical findings in lymph nodes in both HIV-positive and HIV-negative patients. The morphologic findings described should prompt evaluation for infection with Treponema pallidum and, in light of the current epidemic, HIV.
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PMID:Syphilitic lymphadenopathy. Histology and human immunodeficiency virus status. 1047 37

We report three cases of nodal peripheral T-cell lymphoma (PTCL) with Reed-Sternberg-like (RS-like) cells of B-cell pheno- and/or genotype. Histologic analysis in all cases revealed diffuse nodal effacement by atypical lymphoid cells of variable size. Two of the three cases had features of angioimmunoblastic T-cell lymphoma (AILT). Large mononuclear and binucleated cells with prominent eosinophilic nucleoli and abundant cytoplasm resembling classic RS cells and mononuclear variants were scattered throughout all biopsies. The lymphoma cells in the three cases were of T-cell lineage (CD3+, CD43+, and CD45RO+). The RS-like cells from all cases were CD30 and CD15 positive. In contrast to the neoplastic T cells, the RS-like cells lacked all T-cell markers and in two cases were positive for CD20. Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) and EBER 1 (2/2) were detected in the RS-like cells in all cases. The neoplastic T cells were negative for EBV. Polymerase chain reaction (PCR) analysis demonstrated clonal rearrangements of the T-cell receptor gamma chain gene in the three cases. PCR analysis of microdissected RS-like cells for immunoglobulin heavy chain gene rearrangements in cases 1 and 3 showed an oligoclonal pattern. The presence of RS-like cells in PTCL represents a diagnostic pitfall, because in one case this observation led to a misdiagnosis of Hodgkin's disease (HD). The oligoclonal expansion of EBV-infected cells may be related to underlying immunodeficiency associated with T-cell lymphomas and AILT in particular. This phenomenon may provide the basis for some cases of Hodgkin's disease after T-cell lymphomas and suggests that they are clonally unrelated neoplasms. The expression of LMP1 appears to be crucial for the immunophenotype and probably for the morphology of the RS and RS-like cells appearing in diverse lymphoid malignancies, including HD, chronic lymphocytic leukemia, and PTCL.
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PMID:Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection. 1052 24

The recognition of naturally occurring rhadinoviruses in macaque monkeys has spurred interest in their use as models for human infection with Kaposi sarcoma-associated herpesvirus (human herpesvirus 8). Rhesus macaques (Macaca mulatta) and pig-tailed macaques (Macaca nemestrina) were inoculated intravenously with rhadinovirus isolates derived from these species (rhesus rhadinovirus [RRV] and pig-tailed rhadinovirus [PRV]). Nine rhadinovirus antibody-negative and two rhadinovirus antibody-positive monkeys were used for these experimental inoculations. Antibody-negative animals clearly became infected following virus inoculation since they developed persisting antibody responses to virus and virus was isolated from peripheral blood on repeated occasions following inoculation. Viral sequences were also detected by PCR in lymph node, oral mucosa, skin, and peripheral blood mononuclear cells following inoculation. Experimentally infected animals developed peripheral lymphadenopathy which resolved by 12 weeks following inoculation, and these animals have subsequently remained free of disease. No increased pathogenicity was apparent from cross-species infection, i.e., inoculation of rhesus macaques with PRV or of pig-tailed macaques with RRV, whether the animals were antibody positive or negative at the time of virus inoculation. Coinoculation of additional rhesus monkeys with simian immunodeficiency virus (SIV) isolate SIVmac251 and macaque-derived rhadinovirus resulted in an attenuated antibody response to both agents and shorter mean survival compared to SIVmac251-inoculated controls (155.5 days versus 560.1 days; P < 0.019). Coinfected and immunodeficient macaques died of a variety of opportunistic infections characteristic of simian AIDS. PCR analysis of sorted peripheral blood mononuclear cells indicated a preferential tropism of RRV for CD20(+) B lymphocytes. Our results demonstrate persistent infection of macaque monkeys with RRV and PRV following experimental inoculation, but no specific disease was readily apparent from these infections even in the context of concurrent SIV infection.
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PMID:Experimental infection of rhesus and pig-tailed macaques with macaque rhadinoviruses. 1055 50

The CD20 antigen is an attractive target for antibody-directed therapy due to its stable, high-level surface expression on normal and malignant B cells. Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, and Genentech, Inc, San Francisco, CA) is an anti-CD20 chimeric monoclonal antibody that has shown single-agent activity in phase I and II clinical trials in patients with B-cell non-Hodgkin's lymphoma. This antibody has a long serum half-life and low immunogenicity. Infusional symptoms are common with the initial infusion but rare with subsequent treatments. Temporary B-cell depletion occurs but has not been associated with immunodeficiency. The mechanism of action likely includes both immune-mediated effects and direct effects. The generally mild toxicity profile and excellent single-agent activity provide the rationale for use with or following chemotherapy. Additional studies evaluating these and other combinations are under way.
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PMID:Preclinical and phase I and II trials of rituximab. 1056 Oct 21

Inflammatory bowel disease (IBD) is associated with an increased risk of lymphoma, which is usually extraintestinal but sometimes may involve the diseased bowel itself. Most lymphomas described in this setting are of non-Hodgkin's type, but rare cases of Hodgkin's disease (HD) have been reported. We describe the clinicopathologic and molecular features of four patients with primary gastrointestinal HD. Three patients had preexistent Crohn's disease (CD), for which two of them had received immunosuppressive therapy. The fourth patient had a longstanding history of diverticulitis and myasthenia gravis and was receiving immunosuppressive therapy for the latter. Multifocal involvement of the bowel by HD was noted in all four cases. Disease was staged as IVA in one patient, IIIB in one patient, and IE in one patient, and the fourth patient died in the postoperative period before further workup. Two patients received chemotherapy, one of whom was dead at 9 months, whereas the other has no evidence of disease at 25 months' follow-up. The patient with IE disease did not receive any therapy because only a few microscopic foci of disease were present and is also without any evidence of disease at 17 months. The Reed-Sternberg (RS) cells in all four cases expressed CD30, CD15, EBER-1, and LMP-1; two of four were focally CD20-positive. VJ-polymerase chain reaction for immunoglobulin heavy chain (IgH) rearrangement showed a polyclonal pattern in all four cases. In two cases, laser capture microdissection was used to isolate individual RS and Hodgkin's cells, which contained rearranged immunoglobulin genes, confirming a B-cell genotype. Whereas one case showed a dominant clonal band present in all isolates, cells from the patient with stage IE disease clearly showed a polyclonal population of RS cells. Our findings indicate that HD arising in the setting of IBD or chronic inflammation is the result of an Epstein-Barr virus-driven lymphoproliferation, analogous to that found in other immunodeficient states. Disordered immunoregulation inherent to CD and immunosuppressive therapy for the latter may contribute to its development. The finding of polyclonal RS cells in a patient with early stage disease and apparent cure by surgical resection versus monoclonal RS cells in the patient with disseminated disease suggests that HD in the setting of immunodeficiency also may show molecular progression, in a manner similar to that occurring in conventional B-cell lymphoproliferative disorders arising in the same setting.
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PMID:Epstein-Barr virus-positive primary gastrointestinal Hodgkin's disease: association with inflammatory bowel disease and immunosuppression. 1063 89

Human herpes virus, type 8, also called Kaposi's sarcoma-associated virus, is associated with primary effusion lymphoma, an uncommon and unusual subset of acquired immunodeficiency syndrome-related lymphomas mostly confined to body cavities, which primarily affects human immunodeficiency virus-positive men. We report the case of a 40-year-old male with primary effusion lymphoma that presented initially with generalized lymphadenopathy and hepatosplenomegaly, followed by pericardial effusion and cardiac tamponade, in a previously undiagnosed human immunodeficiency virus patient. Cytomorphological studies disclosed a large-cell lymphoma with a population of cells demonstrating intermediate CD45 expression and partial coexpression of CD20 and CD23 markers, as well as universal expression of HLA-DR, CD71, CD38, and CD-30. Molecular studies showed clonal B-cell gene rearrangements and molecular evidence of human herpes virus, type 8. This case stresses the necessity, even in the absence of the 'classical clinical features,' of molecular testing for human herpes virus, type 8 in a subset of patients with high risk for human herpes virus, type 8-associated lymphomas.
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PMID:Unusual presentation of "extracavitary" primary effusion lymphoma in previously unknown HIV disease. 1110 Jun 30

Immunohistochemical studies are increasingly used for the routine diagnosis of lymphomas as it is widely accepted that lymphomas of different cell lineages vary in their prognosis and response to therapy. A case of peripheral T-cell lymphoma with aberrant expression of B-cell-associated antigens L-26 (CD20) and mb-1 (CD 79a) is described. The disease pursued an aggressive clinical course, and the patient died of disease 6 weeks after presentation. Immunohistochemical studies demonstrated expression of both T- and B-cell-associated antigens, including CD3, CD8, CD43, TIA-1, CD20, and CD79a. Other markers expressed by the tumor cells included CD56 and S-100. Of interest, betaF-1 staining for the beta chain of T-cell receptor (TCR) complex was positive in the small admixed T lymphocytes but was negative in the tumor cells, raising the possibility of a gamma/delta T-cell lymphoma. Molecular studies by polymerase chain reaction (PCR) demonstrated clonal TCR-gamma chain gene rearrangement without evidence for a clonal rearrangement of the immunoglobulin heavy chain gene. PCR for HHV-8 related sequences was negative. Mb-1 is an IgM-associated protein that was thought to be restricted to normal and neoplastic B cells. Although its coexpression has been reported in up to 10% cases of precursor T-cell lymphoblastic lymphoma, the coexpression of both CD20 and CD79a has not been described in mature T-cell malignancies. Biphenotypic lymphomas associated with HHV-8 have been reported in immunodeficiency, but no evidence of immune deficiency was identified, and studies for EBV and HHV-8 were negative. This case illustrates that no marker has absolute lineage specificity and that immunophenotypic studies should always be performed with panels of monoclonal antibodies. Moreover, cases with ambiguous phenotypes may require genotypic studies for precise lineage assignment.
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PMID:Peripheral T-cell lymphoma with aberrant expression of CD79a and CD20: a diagnostic pitfall. 1123 1

Chronic lymphocytic leukaemia (CLL) is a disease of late middle age and older. The majority of patients are diagnosed because of a lymphocytosis of at least 5 x 10(9)/L on an incidental blood count. It needs to be distinguished from mantle cell lymphoma and splenic marginal zone lymphoma by lymphocyte markers. The immunophenotype of CLL is sparse surface immunoglobulin, CD5+, CD19+, CD23+, CD79b-, and FMC7-. The disease is staged according to the presence of lymphadenopathy and/or splenomegaly and the features of bone marrow suppression. Most patients have an early stage of disease when diagnosed and perhaps 50% will never progress. This group of patients have a normal life expectancy and do not require treatment beyond reassurance. Progression involves an increasing white cell count, enlarging lymph nodes and spleen, anaemia and thrombocytopenia. Complications of progression include autoimmune haemolytic anaemia and thrombocytopenia, immunodeficiency, and the development of a more aggressive lymphoma. A range of prognostic factors is available to predict progression, but most haematologists rely on close observation of the patient. Intermittent chlorambucil remains the first choice treatment for the majority of patients. Combination chemotherapy offers no advantage. Intravenous fludarabine is probably more effective than chlorambucil, but no trial has yet shown a survival advantage for using it first rather than as a salvage treatment in patients not responding to chlorambucil. It is at least 40 times as expensive as chlorambucil. Cladribine may be as effective as fludarabine, although it has been used less and is even more expensive. Patients who relapse after chlorambucil should be offered retreatment with the same agent and if refractory should be switched to fludarabine, which may also be offered for retreatment on relapse. For patients refractory to both drugs, a variety of options are available. High dose corticosteroids, high dose chlorambucil, CHOP (cyclophosphamide, prednisolone, vincristine and doxorubicin), anti-CD52, anti-CD20 and a range of experimental drugs which are being evaluated in clinical trials. Younger patients should be offered the chance of treatment with curative intent, preferably in the context of a clinical trial. Autologous stem cell transplantation after achieving a remission with fludarabine has relative safety and may produce molecular complete remissions. Only time will tell whether some of these patients are cured but it seems unlikely. Standard allogeneic bone marrow transplant is probably too hazardous for most patients, but non-myeloablative regimens hold out the hope of invoking a graft-versus-leukaemia effect without a high tumour-related mortality. Trials of immunotherapy are exciting options for a few patients in specialised centres.
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PMID:Achieving optimal outcomes in chronic lymphocytic leukaemia. 1136 85


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