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

A 49-year-old man was admitted to our hospital with anemia and hypergammaglobulinemia. Physical examination revealed superficial lymph node swelling and no hepatosplenomegaly. Laboratory findings showed WBC 5,300/microliters with normal hemogram, microcytic and hypochromic anemia. Total protein was 11.5 g/dl and immunoglobulinemia (IgG 10,100 mg/dl, IgA 295 mg/dl, IgM 160 mg/dl) was observed without M-component in serum and urine. The CD4/CD8 ratio of lymphocyte subsets was 0.58 and the tuberuculin skin test was negative. Urinary protein was positive and renal biopsy disclosed plasma cell infiltration. Lymph node biopsy revealed multiple lymphoid follicles and infiltration of plasma cells in the interfollicular areas. A diagnosis of multicentric Castleman's disease (MCD) was made baredon clinical findings and lymph node biopsy. After therapy with plasmapheresis and the CHOP regimen, he was given etoposide. Although discharged with clinical improvement and a decrease of serum IgG, he was readmitted because of pyrexia after 4 days and died of pneumonia with adult respiratory distress syndrome. The autopsy revealed lymphoid interstitial pneumonia. It seems important to notice that some of MCD have poor prognoses because of accompanying immunodeficiency.
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PMID:[Multicentric Castleman's disease with lymphoid interstitial pneumonia died of aggressive course with adult respiratory distress syndrome]. 756 7

Human herpesvirus-8 (HHV-8) DNA sequences have been reported to be strictly associated not only with various forms of Kaposi's sarcoma but also with an unusual subgroup of acquired immunodeficiency syndrome (AIDS)-related B-cell lymphomas. A possible relation of this putative virus also with multicentric Castleman's disease (MCD) has been recently suggested. We used polymerase chain reaction to look for the presence of HHV-8 sequences in a well characterized series of benign, atypical, and malignant lymphoid tissues from 45 Hodgkin's disease and 43 non-Hodgkin's lymphoma (NHL) cases, as well as from 5 MCD, 15 angioimmunoblastic lymphadenopathy (AILD), and 23 benign lymphadenopathy cases. Among the 38 AIDS-related lymphoid lesions, only 1 NHL and 1 persistent generalized lymphadenopathy (PGL) case were positive. Furthermore, among the 92 non-AIDS-related lymphoproliferative disorders, HHV-8 sequences were detected in 3 classic AILD cases and in 4 reactive lymphadenopathies. Six of 9 HHV-8 positive lymphoid lesions (1 NHL, 1 PGL, 1 AILD, and 3 reactive lymphadenopathy cases) were also positive for Epstein-Barr viral sequences. The four human immunodeficiency virus (HIV) negative lymphadenopathies positive for HHV-8 sequences showed an almost identical histology, characterized by a predominantly follicular lesion, with giant germinal center hyperplasia, and increased vascularity, resembling HIV-related lymphadenopathy and MCD. Our results, while providing the first evidence of the presence of HHV-8 sequences in AILD cases, suggest a possible association of these herpes viral sequences with a distinct histologic type of non-neoplastic lymphadenopathy, not associated with other common herpes infections.
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PMID:Human herpesvirus-8 DNA sequences in human immunodeficiency virus-negative angioimmunoblastic lymphadenopathy and benign lymphadenopathy with giant germinal center hyperplasia and increased vascularity. 861 19

Profound immunodeficiency in multicentric Castleman's disease has already been elucidated. In the present study, we investigated CD45RO and Fas antigen expression and apoptosis by T cells in three patients with this disease. T cell expression of CD45RO and Fas antigen was increased in two of the three patients, indicating in vivo lymphocyte activation. Apoptosis of T cells from the two patients with increased CD45RO and Fas antigen expression occurred after overnight culture in the presence of pokeweed mitogen. Occurrence of apoptosis was indicated by DNA laddering and nuclear chromatin condensation. Peripheral blood mononuclear cells from the two MCD patients revealed spontaneous apoptosis following 3 days of culture by quantitative assay using flow cytometry. These findings show that T cells are activated in some patients with multicentric Castleman's disease and suggest that this activation may promote apoptosis.
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PMID:Apoptosis of T cells in multicentric Castleman's disease. 863 86

Despite extensive epidemiological evidence suggesting that Kaposi's sarcoma (KS) has an infectious origin, a specific viral association with KS had not been documented until recently, when two novel DNA fragments were identified in KS lesional tissue from a patient with the acquired immunodeficiency syndrome (AIDS). These fragments belong to a previously unidentified human herpesvirus, called KS-associated herpesvirus (KSHV), or human herpesvirus 8. Although this virus is generally absent from normal control tissues, inflammatory conditions, and a variety of tumors, it is present in most AIDS- as well as non-AIDS-related KS lesions, suggesting that it is not simply an opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Furthermore, this virus is consistently present in a specific type of non-Hodgkin's lymphoma, frequently although not exclusively occurring in patients with AIDS (namely, the primary effusion lymphomas, previously called body cavity-based lymphomas). KSHV is also present in a significant proportion of cases of AIDS- and non-AIDS-related multicentric Castleman's disease. Sequence analysis has led to the identification of genes in the KSHV genome that may have important pathobiological functions, and experimental approaches have been developed to isolate, grow and transmit KSHV in vitro. An understanding of KSHV is important for evaluating its role in the pathogenesis of Kaposi's sarcoma, primary effusion lymphomas, and multicentric Castleman's disease, and to help develop better methods for the prevention and treatment of these diseases.
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PMID:Kaposi's sarcoma-associated herpesvirus: a lymphotropic human herpesvirus associated with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. 904 10

The epidemiologic link between multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) and the high frequency of KS herpesvirus (KSHV) detection in both diseases raise the question of a role of this new virus in the pathogenesis of MCD. To explore this hypothesis, the KSHV DNA load was investigated in peripheral blood mononuclear cells of 3 human immunodeficiency virus (HIV)-infected patients with MCD at different points during the clinical course. Clinical parameters, such as fever and the presence of lymphadenopathy, were systematically assessed. Hemogram and C-reactive protein level determinations were performed as standard procedures. KSHV DNA load was investigated by means of semiquantitative polymerase chain reaction assay using peripheral blood mononuclear cells of the patients. A correlation between the variation in clinical and biologic parameters related to MCD and KSHV DNA load was found, suggesting a close relationship between KSHV and MCD in HIV-1-infected patients.
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PMID:Exacerbations of clinical symptoms in human immunodeficiency virus type 1-infected patients with multicentric Castleman's disease are associated with a high increase in Kaposi's sarcoma herpesvirus DNA load in peripheral blood mononuclear cells. 912 85

Kaposi's sarcoma-associated herpes virus (KSHV), also designated human herpesvirus 8 (HHV8), has been detected consistently in Kaposi's sarcoma, body cavity lymphoma and multicentric Castleman's disease, both in human immunodeficiency virus (HIV)-positive and -negative patients. Identification of KSHV/HHV8 DNA sequences in various benign and malignant vascular tumors in HIV-negative patients was reported in one study, but was not confirmed in several other studies. The vascular lesions, other than Kaposi's sarcoma, in which sequences could not be detected have included malignant vascular tumors of serous membranes, infantile capillary hemangiomas, and several benign and malignant vascular tumors of the spleen. We studied 30 primary benign and malignant vascular tumors of the liver; KSHV/HHV8 DNA sequences could not be detected in any. We conclude that this virus plays no role in the etiology of vascular tumors of the liver.
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PMID:Absence of human herpesvirus 8 DNA sequences in vascular tumors of the liver. 958 71

Kaposi's sarcoma (KS) is a vascular tumor predominantly found in the immunosuppressed. Epidemiologic studies suggest that an infective agent is the etiologic culprit. Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8 (HHV-8), is a gamma human herpesvirus present in all epidemiologic forms of KS and also in a rare type of a B cell lymphoma, primary effusion lymphoma (PEL). In addition, this virus is present in most biopsies from human immunodeficiency virus (HIV)-associated multicentric Castleman's disease (MCD). MCD is a lymphoproliferative disorder with, like KS, a prominent microvasculature. The genome of KSHV contains the expected open reading frames (ORFs) encoding for enzymes and viral structural proteins found in other herpesviruses, but it also contains an unprecedented number of ORFs pirated during viral evolution from cellular genes. These include proteins that may alter cellular growth (e.g., Bcl-2 and cyclin homologs), induce angiogenesis (e.g., chemokine, chemokine receptor, and cytokine homologs), and regulate antiviral immunity (e.g., CD21 and interferon regulatory factor homologs). No ORF with sequence similarity to the Epstein-Barr nuclear antigens (EBNAs) and latent membrane proteins (LMPs) of Epstein-Barr virus (EBV) is present, but proteins analogous to these in structure and in latent expression are found [e.g., ORF 73 encoding for KSHV latent nuclear antigen (LNA-1) and K12 encoding for a possible latent membrane protein]. Current serologic assays confirm the strong association of infection with KSHV and risk of KS development. The mechanism of how this new virus may trigger the precipitation of KS is still unclear.
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PMID:Kaposi's sarcoma-associated herpesvirus. 970 7

Human herpesvirus 8 (HHV-8) infection has been implicated in the etiology of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), three diseases that frequently develop in immunocompromised, human immunodeficiency virus-positive individuals. One hypothesis that would account for different pathological manifestations of infection by the same virus is that viral genes are differentially expressed in heterogeneous cell types. To test this hypothesis, we analyzed the localization and levels of expression of two viral genes expressed in latent and lytic infections and the viral homologue of interleukin-6 (vIL-6). We show that PEL parallels KS in the pattern of latent and lytic cycle viral gene expression but that the predominant infected cell type is a B cell. We also show that MCD differs from KS not only in the infected cell type (B-cell and T-cell lineage) but also in the pattern of viral gene expression. Only a few cells in the lesion are infected and all of these cells express lytic-cycle genes. Of possibly greater significance is the fact that in a comparison of KS, PEL, and MCD, we found dramatic differences in the levels of expression of vIL-6. Interleukin-6 is a B-cell growth and differentiation factor whose altered expression has been linked to plasma cell abnormalities, as well as myeloid and lymphoid malignancies. Our findings support the hypothesis that HHV-8 plays an important role in the pathogenesis of PEL and MCD, in which vIL-6 acts as an autocrine or paracrine factor in the lymphoproliferative processes common to both.
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PMID:Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. 1019 14

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystemic disorder associated with osteosclerotic myeloma and multicentric Castleman's disease (MCD). Human herpesvirus type 8 (HHV-8) DNA sequences have been detected in lymph nodes of about 40% of human immunodeficiency virus (HIV)-negative patients with MCD, and in bone marrow stromal cells of patients with multiple myeloma. Considering these data, we investigated the presence of HHV-8 in 18 patients with POEMS syndrome (9 with MCD), by nested polymerase chain reaction (N-PCR) to detect DNA sequenses in various cells and tissues obtained by biopsy or at autopsy (13 patients, of whom 7 had MCD), and by an immunofluorescence assay to detect anti-HHV-8 IgG antibodies in blood (18 patients, of whom 9 had MCD). Detection of HHV-8 DNA was performed using three different N-PCR, targeting nonoverlapping regions in open reading frame (ORF) 25 and ORF26. Seven of 13 (54%) POEMS patients had HHV-8 DNA sequences in their tissues, as assessed by all three N-PCR, and 9 of 18 (50%) had circulating anti-HHV-8 antibodies. HHV-8 was mainly detected in the subset of POEMS patients with MCD (6 of 7 [85%] for DNA sequences; 7 of 9 [78%] for antibodies). The percentage of positive N-PCR was higher in lymph nodes than in bone marrow samples (P <.02). Sequencing of amplicons showed a homogeneous restricted variability in the ORF26 region, characteristic of the minority subgroup B defined by Zong, and responsible for isoleucine and glycine substitutions at amino acid positions 134 and 167. These findings strongly suggest an association of HHV-8 infection with POEMS syndrome-associated MCD.
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PMID:Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman's disease. 1033 70

Human herpesvirus-8 (HHV-8) has been associated with Kaposi's sarcoma, multicentric Castleman's disease and primary effusion lymphoma. Kaposi's sarcoma and multicentric Castleman's disease patients may develop body cavity effusions that, unlike primary effusion lymphoma, are poorly characterized. To better define these effusions, pleural and peritoneal fluids derived from 12 human immunodeficiency virus-seropositive and one seronegative patients affected by Kaposi's sarcoma or multicentric Castleman's disease were analyzed by a combination of morphologic, immunophenotypic, and DNA analyses, including polymerase chain reaction amplification of HHV-8, Epstein-Barr virus, and immunoglobulin heavy-chain (IgH) gene sequences. In addition, HHV-8 serologic status was assessed by using an immunofluorescence assay. All patients were adult men with high antibody titers to HHV-8; 11 of the 13 patients were homosexual/bisexual. Effusions revealed monocyte/macrophage-rich infiltration (10 patients) or large-cell lymphoma with CD45(+)/non-T/non-B phenotype (three of 13 patients); polymerase chain reaction analysis showed the presence of HHV-8 sequences (nine of 13 patients), germline IgH (seven of 12 patients) or clonal IgH rearrangements (four of 12 patients), and rarely Epstein-Barr virus sequences (two of 12 patients). In the setting of HHV-8 infection, two effusion types may occur. One fulfills the criteria for HHV-8-positive PEL (lymphoma-morphology, HHV-8-DNA(+), IgH rearrangement). The other seems more reminiscent of an HHV-8-associated nonneoplastic process (monocyte-macrophage morphology, HHV-8-DNA(+/-), germline IgH). Interestingly, a single case of the latter effusion type harbored a B-cell monoclonal proliferation, which suggests the hypothesis that a prelymphomatous effusion may precede overt body cavity lymphoma.
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PMID:Human herpesvirus-8 in lymphomatous and nonlymphomatous body cavity effusions developing in Kaposi's sarcoma and multicentric Castleman's disease. 1059 87


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