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 tumor necrosis factor receptor family molecule CD30 is expressed by activated and memory T cells, depending on IL-4 stimulation preferentially in association with Th0- and Th2-type responses. It mediates pleiotropic effects primarily of the inhibitory type. Arguing that CD30(+) cells have a peculiar redistribution in disease, it is demonstrated here, in the Hodgkin-derived L540 cell line (an established model for studying CD30 signaling), that CD30 regulates the prototypic lymphoid chemokine receptor CXCR4 (CD184), which plays an important role in many organ systems and is a coreceptor for human immunodeficiency virus-1 entry. CD30 stimulation with agonistic antibodies in L540 cells led to the accumulation of CXCR4 mRNA, which reached a plateau after 4 hours and did not require protein synthesis. It has been reported recently that CD30 up-regulates the transcription of CCR7 mRNA in YT lymphoma cells. After mRNA transcription, membrane expression of CXCR4 in L540 cells increased as early as 12 hours, reached a plateau after 24 hours (MFI +/- SD, 839 +/- 122 vs basal 168 +/- 28; P <.01) and was still increased after 5 days, permitting enhanced sensitivity to the chemotactic activity of CXCR4-ligand CXCL12 (CI +/- SD, 10 +/- 1 vs basal 5 +/- 2; P <.01). CD30 cross-linking also induced the release of CCL5 and CCL3 and the up-regulation of membrane binding capacity for CCL3 and CCL4 and decreased proliferative activity. This new regulatory role of CD30 may be relevant for T-cell maturation and effector responses and for promoting cancer biology.
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PMID:CD30 triggering by agonistic antibodies regulates CXCR4 expression and CXCL12 chemotactic activity in the cell line L540. 1175 52

Human herpesvirus type 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is frequently identified in tumor tissue obtained from human immunodeficiency virus (HIV)-infected patients with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), or multicentric Castleman's disease. The association between HHV-8 and acquired immunodeficiency syndrome (AIDS)-associated solid lymphomas is less clear. Herein, I describe the case of a man with a CD4+ count of 30 cells/microL, and HIV viral load of 90,000 copies/mL, multi-drug resistant HIV infection, and limited stage KS. Biopsy of a progressive dorsal foot rash revealed a dense, deep, lymphoid infiltrate that extended into papillary dermis but without epidermotrophism. Microscopy showed a homogeneous population of anaplastic large B cells that stained positive for CD20 (L26), CD30, and lambda light chain. In situ hybridization of tumor tissue identified Epstein-Barr virus (EBV)-encoded RNA, and polymerase chain reaction amplification yielded HHV-8-specific gene products. Staging studies did not reveal lymphoma elsewhere, and the patient began chemotherapy, but died from septic complications. Autopsy was notable only for the presence of a consolidative pneumonia. Although extranodal presentations are common in the setting of immunodeficiency, reports of AIDS-associated lymphoma presenting as a nonepidermotrophic foot lesion are rare. Such a presentation serves to broaden the differential of skin and foot lesions in the setting of HIV infection. More importantly, this case provides further support that HHV-8 can be associated with solid lymphomas that have an anaplastic large cell morphology.
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PMID:HHV-8- and EBV-associated nonepidermotrophic large B-cell lymphoma presenting as a foot rash in a man with AIDS. 1201 67

Plasma levels of cytomegalovirus (CMV)-specific immunoglobulin G (IgG), soluble (s) CD30, sCD26 (dipeptidyl peptidase IV [DPP IV]) enzyme activity, and tumor necrosis factor receptor-I (TNFR-I) were assessed in human immunodeficiency virus (HIV)-infected patients who experienced CMV retinitis (CMVR) as an immune restoration disease (IRD) during their first 6 months of highly active antiretroviral therapy (HAART) and in CMV-seropositive, HIV-infected patients with similar baseline CD4(+) T cell counts who had uneventful immune reconstitution. Patients who experienced CMVR IRD had a significant increase in CMV-specific IgG during their first 12 months of HAART, indicating restored CMV-specific immune responses. They also had significantly higher levels of sCD30 both before HAART and for up to 12 months after start of treatment. sCD30 levels remained elevated during 48 months of HAART, suggesting persistence of a predominant Th2 cytokine environment. Levels of sCD26 (DPP IV) enzyme activity and TNFR-I did not differ significantly between the 2 groups at any time point.
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PMID:Cytomegalovirus (CMV) retinitis immune restoration disease occurs during highly active antiretroviral therapy-induced restoration of CMV-specific immune responses within a predominant Th2 cytokine environment. 1208 31

Suppression of HIV replication by antiretroviral therapy has various effects on the immune system of HIV-infected patients. Whereas protective pathogen-specific immune responses are restored in some patients, others have persistent immunodeficiency or produce immunopathological responses against opportunistic pathogens that cause immune restoration disease (IRD). Significant morbidity and even mortality may result from IRDs associated with infections by mycobacteria, herpesviruses, hepatitis viruses or the JC virus. Preliminary evidence from our studies suggests that immune responses in patients with IRD may be dysregulated and affected by immunogenetic factors. Thus, herpesvirus IRDs were associated with increased plasma levels of bioavailable interleukin-6 and soluble CD30, while mycobacterial and herpesvirus IRDs were associated with a major histocompatibility complex gene haplotype and/or alleles of particular cytokine genes. A greater understanding of pathogenic mechanisms and the immunogenetics of IRDs may lead to improved preventive and management strategies.
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PMID:Immune restoration disease in HIV patients: aberrant immune responses after antiretroviral therapy. 1255 88

The human CD30 gene, found on chromosome 1; 1p36, contains a microsatellite of the type [(CCAT)2-12CCACTTATGCAT]n within the promoter. As the microsatellite has been shown to be both polymorphic and involved in the transcriptional regulation of this gene, it is of potential interest with respect to interindividual differences in CD30 expression. Here we describe a method for determining length variation of this repeat region and determine the frequency and distribution of alleles of the CD30 microsatellite within the Western Australian population. As soluble CD30 levels are predictive for disease associated with human immunodeficiency virus (HIV)-1 infection, we also determined allele frequencies in an HIV+ cohort.
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PMID:Distribution of human CD30 gene promoter microsatellite alleles in healthy and human immunodeficiency virus-1 infected populations. 1264 80

We report a case of plasmablastic lymphoma presenting in cervical lymph nodes in an 82-year-old, human immunodeficiency virus-negative man. Cytologic and histologic examinations demonstrated a large cell lymphoma with plasmacytic differentiation. The tumor cells were positive for CD138, CD38, epithelial membrane antigen, CD30, and lysozyme, but lacked expression of leukocyte common antigen, T-cell, and B-cell markers. Abundant Epstein-Barr virus-encoded RNA transcripts were identified by in situ hybridization. A monoclonal rearrangement of kappa-light- chain gene was demonstrated. The cytologic, histologic, immunohistochemical, and molecular features of plasmablastic lymphoma are reviewed. The potential diagnostic pitfalls and differential diagnoses, especially in a fine-needle aspiration specimen, are addressed.
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PMID:Plasmablastic lymphoma of the cervical lymph nodes in a human immunodeficiency virus-negative patient: a case report and review of the literature. 1508 96

Human herpesvirus 8 (KSHV/HHV-8) is associated with all forms of Kaposi sarcoma (KS), with a rare high-grade B-cell non-Hodgkin lymphoma characterized by serous effusions in body cavities called primary effusion lymphoma (PEL) and with some forms of multicentric Castleman disease (MCD). Although mostly observed during AIDS, such disorders have also been described with a lower incidence in human immunodeficiency virus-negative patients. We describe here the features of two novel cases of AIDS-unrelated PEL. Two patients, a 78-year-old man (case 1) and a 86-year-old woman (case 2), both of French origin, presented exudative ascitic effusion containing numerous KSHV/HHV-8(+) EBV(-) large lymphomatous cells of B-cell clonal origin, characterized by a CD45(+) CD30(+) CD19(-) CD20(-) immunophenotype. The PEL tumor cells harbored a homogenous and isolated trisomy 12 in case 1 and an aberrant expression of the T-cell lineage antigen CD7 in case 2. Both patients were lymphopenic at the time of PEL diagnosis and rapidly died with progressive lymphoma. Moreover, patient 2 had a previous history of classic KS and MCD clinically improved after treatment with all-trans-retinoid acid and a concomitant metastatic breast adenocarcinoma. Compared to AIDS-related PEL, these two cases displayed distinct features in particular the advanced age of patients, as observed for Mediterranean KS, and the absence of EBV coinfection.
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PMID:Human herpesvirus 8 (HHV-8)-associated peritoneal primary effusion lymphoma (PEL) in two HIV-negative elderly patients. 1511 7

Primary effusion lymphoma (PEL) is recognized as a unique clinicopathological entity associated with human herpesvirus 8 (HHV-8), and it occurs almost exclusively in human immunodeficiency virus (HIV)-infected individuals. In the majority of PEL cases, Epstein-Barr virus (EBV) has been found in the tumor cells as well. We describe here an elderly HIV seronegative female patient with PEL in the pleura and pericardium not associated with HHV-8 or EBV. Cytologic examinations of the pleural effusion revealed large lymphoma cells with immunophenotypes positive for CD8, CD10, CD19, CD20, CD22, CD24, CD45, and HLA-DR but negative for CD30 and surface immunoglobulin. Chromosome analysis showed complicated abnormalities including add(3)(q27). Immunoglobulin gene rearrangement was detected by Southern blotting; however, c-myc, Bcl-2, and Bcl-6 genes were not rearranged. The patient was treated with a modified CHOP (cyclophosphamide, hydroxydoxorubicin, oncovine, and prednisolone) regimen, and achieved remission. Recurrence of PEL in the pericardium as effusion lymphoma was found 3 months after the discontinuation of CHOP. After approximately 1 year of intermittent multiagent salvage therapy for pericardial recurrences, a treatment that resulted in a partial response, 3 cycles of monotherapy with sobuzoxane were administered. At the time of this report the patient had been free from PEL for more than 18 months without chemotherapy.
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PMID:Durable remission by sobuzoxane in an HIV-seronegative patient with human herpesvirus 8-negative primary effusion lymphoma. 1516 97

The main topic of this article is B cell development and differentiation, with a special focus on the mechanisms and molecules that regulate the expression of humoral immunity. Molecular epidemiological analysis was performed on the genes responsible for the X-linked agammaglobulinemia (XLA) phenotype of the majority of Italian patients and their distinct mutations were characterized. Mutations in Bruton's tyrosine kinase (BTK), a member of Tec Family of protein tyrosine kinases, have been found to be mainly responsible for XLA disease. The exact function of BTK in signal transduction is not yet known; thus, the specific role of BTK in receptor-dependent calcium signaling and the pro-antiapoptotic regulatory activity was addressed by transfecting RAMOS-1, a BTK-deficient human Burkitt's/B cell leukemia line with wild-type and mutant constructs. This work may provide clues about critical sites in the molecule and give support for gene therapy as a potential successful approach to XLA. Another aspect of this research is the identification and dissection of the molecular events that are likely to be directly related to the ability to express various isotypes of immunoglobulin with differing function and certain B cell immunodeficiency, mainly common variable disease and non-X-linked hyperIgM. B cell development and maturation steps in different compartments of the immune system are tracked by the analysis of cell-surface molecules and components of the signal transduction pathways, i.e. CD40, CD30, CD27, CD38, CD22 and CD24. A few components involved in B cell development, maturation and differentiation and their specific functional role are at least partially known, but these are far from fitting into an understandable pathway at present.
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PMID:Insight into B cell development and differentiation. 1517 20

Immune Restoration Diseases (IRD) are a collection of atypical 'opportunistic infections' and inflammatory diseases seen in human immunodeficiency virus (HIV) patients after HIV viraemia is suppressed by highly active antiretroviral therapy (HAART). IRD probably reflect dysregulated immune responses against pre-existing infections by opportunistic pathogens, with different immunopathological mechanisms for different pathogens. For example, mycobacterial IRD are associated with delayed type hypersensitivity (DTH) responses to mycobacterial antigens, whereas patients who experience cytomegalovirus (CMV) IRD have elevated plasma levels of soluble CD30, a marker of a T2 cytokine environment expressed by activated CD8 T-cells. As IRD are often compartmentalised to organs, monitoring serological markers such as pathogen-specific IgG antibody, may be informative, as demonstrated for CMV and hepatitis C virus (HCV)-associated IRD. Genetic studies have provided evidence of distinct immunopathological mechanisms and inherited susceptibility to IRD associated with mycobacterial and herpesviridae infections. The expansion of HAART in the developing world where many HIV patients have low CD4+ T-cell counts and high rates of concomitant infections will place a large number of patients at-risk of developing IRD. It is therefore important to understand the immunopathology so that prevention, diagnosis and treatment can be improved.
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PMID:Immune restoration disease: a consequence of dysregulated immune responses after HAART. 1527 87


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