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)

A panel of human hematopoietic cell lines was genetically engineered to express recombinant complement receptor 2 (CR2 or CD21), which is also the Epstein-Barr virus (EBV) receptor. The panel was composed of SupT1, J1.1, and U1.HIV cells. The latter is a promonocytic cell line, whereas the other two are T lymphocytic cell lines. J1.1 and U1.HIV cells are latently infected by human immunodeficiency virus type 1 (HIV-1). These three cell lines were transduced with a murine leukemia virus (MLV)-based retroviral vector system. CR2 was efficiently and consistently expressed on the cell membranes, conferring enhanced susceptibility to EBV infection. The efficient expression of recombinant CR2 in cell lines of hematopoietic origin allowed for study of the interaction between EBV infection and HIV-1 gene regulation in suitable cell-culture models. The effects of EBV and HIV-1 coinfection results were cell-type dependent. In the two T lymphocytic cell lines, HIV-1 expression was rapidly and persistently down-regulated by EBV. Conversely, in the promonocytic cell line U1.HIV-CR2, HIV-1 expression was transiently enhanced by EBV. The EBV and HIV-1 coinfection result in U1.HIV-CR2 cells is potentially important, as the activation of HIV-1 gene expression in monocyte-like cells may play a crucial role in the mechanism of CD4+ T cell depletion by apoptosis. Therefore, the U1.HIV-CR2 cell line may represent a useful cell-culture system to study the synergism between EBV and HIV-1 in inducing apoptosis in primary CD4+ T cells.
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PMID:Differential effects on HIV-1 gene regulation by EBV in T lymphocytic and promonocytic cells transduced to express recombinant human CR2. 934 4

Smooth muscle tumors (leiomyosarcomas) are the second most prevalent malignancy of children with the acquired immunodeficiency syndrome (AIDS). We have investigated the tumors, plasma, and peripheral white blood cells of eight children with AIDS with smooth muscle tumors for evidence of tumor association with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). Very low levels of HIV were found in the tumors of the AIDS patients, probably resulting from blood-borne carriage of virus. These smooth muscle tumors had very high quantities of EBV in all the tumor cells by in situ hybridization, with an average of 4.5 EBV genomes per cell by quantitative polymerase chain reaction amplification. Increased amounts of EBV were found in the peripheral blood cells of two AIDS patients before the time of tumor diagnosis. EBV clonality studies demonstrated different monoclonal EBV infection of two separate colonic tumors from one patient, and dual or mixed monoclonal EBV infection in another patient. The muscle cells of leiomyomas and leiomyosarcomas of patients with AIDS demonstrated prominent staining with antibodies to the EBV receptor. The uniform distribution and striking amount of EBV in the tumor cells demonstrates that EBV is capable of infecting smooth muscle cells and that these cells support EBV replication. Clonal EBV proliferation suggests that EBV infection occurs at an early stage of tumor development. These findings indicate that EBV has a causal role in the oncogenesis of leiomyosarcomas of patients with AIDS.
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PMID:Benign and malignant smooth muscle tumors containing Epstein-Barr virus in children with AIDS. 940 27

Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcRgammaIII, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission.
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PMID:Tonsil epithelial factors may influence oropharyngeal human immunodeficiency virus transmission. 1762 Mar 69

Complement receptor 2-negative (CR2/CD21(-)) B cells have been found enriched in patients with autoimmune diseases and in common variable immunodeficiency (CVID) patients who are prone to autoimmunity. However, the physiology of CD21(-/lo) B cells remains poorly characterized. We found that some rheumatoid arthritis (RA) patients also display an increased frequency of CD21(-/lo) B cells in their blood. A majority of CD21(-/lo) B cells from RA and CVID patients expressed germline autoreactive antibodies, which recognized nuclear and cytoplasmic structures. In addition, these B cells were unable to induce calcium flux, become activated, or proliferate in response to B-cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. Moreover, gene array analyses of CD21(-/lo) B cells revealed molecules specifically expressed in these B cells and that are likely to induce their unresponsive stage. Thus, CD21(-/lo) B cells contain mostly autoreactive unresponsive clones, which express a specific set of molecules that may represent new biomarkers to identify anergic B cells in humans.
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PMID:Complement receptor 2/CD21- human naive B cells contain mostly autoreactive unresponsive clones. 2105 68

B cells represent one of the cellular components of the immune system that protects the individual from invading pathogens. In response to the invader, these cells differentiate into plasma cells and produce large amounts of antibodies that bind to and eliminate the pathogen. A hallmark of autoimmune diseases is the production of autoantibodies i.e. antibodies that recognize self. Those that are considered pathogenic can damage tissues and organs, either by direct binding or when deposited as immune complexes. For decades, B cells have been considered to play a major role in autoimmune diseases by antibody production. However, as pathogenic autoantibodies appear to derive mainly from T cell dependent responses, T cells have been the focus for many years. The successful treatment of patients with autoimmune diseases with either B cell depletion therapy (rituximab) or inhibition of B cell survival (belimumab), suggested that not only the autoantibodies but also other B cell features are important. This has caused a surge of interest in B cells and their biology resulting in the identification of various subsets e.g. regulatory B cells, several memory B cell subsets etc. Also, in other conditions such as chronic viral infections and primary immunodeficiency, several B cell subsets with unique characteristics have been identified. In this review, we will discuss one of these subsets, a subset that is expanded in conditions characterized by chronic immune stimulation. This B cell subset lacks, or expresses low, surface levels of the complement receptor 2 (CD21) and has therefore been termed CD21(-/low) B cells.
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PMID:CD21 -/low B cells: A Snapshot of a Unique B Cell Subset in Health and Disease. 2611 82

Hyperimmunoglobulin E syndromes (HIES) are rare primary immunodeficiency diseases characterized by markedly elevated serum immunoglobulin (Ig) E, recurrent pneumonia, and chronic eczema. To date, information about pediatric HIES is limited. We aimed to evaluate the spectrum of clinical and immunological features in pediatric patients with HIES in China.We retrospectively reviewed the cases of 4 pediatric patients with HIES followed at the Guangzhou Women and Children's Medical Center from May 2013 to September 2017. We analyzed clinical presentation, laboratory data, immunological evaluations, imagenological characteristics, treatment, response to therapy, genetic and bronchoalveolar lavage fluid (BALF) findings, and prognosis.The common clinical features of the patients were recurrent respiratory and mucocutaneous infections and eczematoid skin lesions. In 3 of 4 patients, BALF and transbronchial lung biopsy (TBLB) demonstrated fungal pneumonia with organisms including invasive Aspergillus and Penicillium marneffei. Elevated serum IgG and IgM were detected in 3 and 2 cases, respectively, while CD4+ T and CD19+ B cells were slightly reduced in only 1 patient. Nitroblue tetrazolium tests (NBTs) were normal in all patients, and reduced natural killer cell counts were identified in 3 patients. A novel missense mutation in exon 17 (c.1593A>T, p.K531N) was identified in the signal transducer and activator of transcription 3 (STAT3) gene that has not been reported previously. One patient had 3 homozygous nonsynonymous variations of the complement receptor 2 (CR2) gene distributed in exons 10 (c.1916G>A, p.S639N) and 11 (c.1987T>C, p.S663P and c.2012G>A, p.R671H) with high frequency.This case series suggests that fungi are important respiratory pathogens in children with HIES and should be considered in cases of pneumonia in this population. The NIH scoring system does not allow diagnostic certainty, particularly in infants, because some of the common manifestations of HIES may not develop until the patient matures. Pulmonary complications must be identified in the early stage of the disease to treat them effectively. In addition, we report a mutation in STAT3 that has not been identified previously.
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PMID:Pediatric hyperimmunoglobulin E syndrome: A case series of 4 children in China. 2962 Jun 31


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