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 unique manifestation of the inherited immunodeficiency, X-linked lymphoproliferative disease (XLP), is the impaired control of EBV infection. The gene, which carries mutations or is deleted in the patients, has been identified (Xq25). The encoded protein (SAP, 128 aa) contains a single SH2 domain and binds to signaling lymphocytic activation molecule (SLAM) and to other related surface molecules that are expressed on activated T, B and NK cells. SAP modifies signal transduction through its association with these molecules. Initially it was assumed that SAP acts passively by interfering and blocking active interactions involving other SH2 carrying molecules. We demonstrated that SAP protein is expressed in activated T and NK, but not in activated B cells. This finding is in line with the fact that in vitro performance of effector cells derived from XLP patients is impaired. However, it is still not known why the severe symptoms (fatal mononucleosis or malignant lymphoproliferation in the survivors of the primary infection) are elicited by EBV. We studied SAP expression in several Burkitt lymphoma (BL) derived lines. In contrast to normal B cells, certain lines expressed SAP. These were all type I cells in the Burkitt line nomenclature: they expressed only one of the EBV encoded proteins (EBNA-1) and their phenotype corresponded to resting B cells. Lymphoblastoid cell lines and type III BLs, whose phenotype resembled activated B cells and expressed all nine EBV encoded proteins, were devoid of SAP. The relationship between cell activation and SAP expression is reciprocal in T and B cells i.e. BL lines, activated T and NK cells express SAP, while BL blasts do not express SAP. This opposite relationship may be exploited for studies about the function of SAP.
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PMID:The X-linked lymphoproliferative disease gene product SAP is expressed in activated T and NK cells. 1200 45

The relationship between Epstein Barr Virus (EBV) and the human host is commonly benign, whereas the development of malignancy is most likely due to imbalance between the virus and host's immune system. The aim of this study was to analyze the association of EBV with pediatric lymphomas in human immunodeficiency virus (HIV) patients. Four consecutive patients with a histological and clinical diagnosis of lymphomas among 351 pediatric HIV-infected children prospectively followed up at our hospital since 1991 were studied. The cases included one diffuse fibrosis lymphocyte depletion subtype Hodgkin's lymphoma, 2 Burkitt's lymphomas, and one primary diffuse large B-cell lymphoma of the central nervous system. We assessed EBV presence by LMP-1 protein labeling by immunohistochemistry and in situ hybridization for EBERs in formalin-fixed and paraffin-embedded biopsies from all four cases. All HIV-associated lymphomas studied were found to be associated with EBV. The lymphoproliferative action of EBV may induce oncogenesis by increasing the probability of genetic alterations and/or by expanding an already malignant clone. As an oncogenic protein, LMP-1 expression by tumor cells supports the involvement of EBV in disease pathogenesis.
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PMID:Epstein Barr virus-associated lymphoma in HIV-infected children. 1209 68

The SH2 domain containing SH2D1A protein has been characterized in relation to the X-linked lymphoproliferative disease (XLP), a primary immunodeficiency that leads to serious clinical conditions after Epstein-Barr virus (EBV) infection. The SH2D1A gene is mutated in the majority of XLP patients. We previously detected SH2D1A in activated T and NK cells, but not in B lymphocytes. We have found SH2D1A protein in Burkitt lymphoma (BL) lines, but only in those that carried EBV and had a Group I (germinal center) phenotype. All the EBV-carrying Group III (immunoblastic) and the EBV-negative BL lines tested were SH2D1A-negative. Motivated by these differences, we studied the impact of EBV and the cellular phenotype on SH2D1A expression. We approached the former question with BL sublines after both the loss of the virus and subsequent reinfection. We also tested original EBV-negative BL lines carrying transfected EBV genes, such as EBNA1, EBNA2, EBNA6, EBER1, 2 and LMP1, respectively. In our experiments, no direct relationship could be seen between EBV and SH2D1A expression. We modified the phenotype of the Group I BL cells by LMP1 transfection or CD40 ligation. The phenotypic changes, indicated by expression of immunoblastic markers, e.g., SLAM, were accompanied by downregulation of SH2D1A. It seems, therefore, that the presence of EBV and the phenotype of the cell together regulate SH2D1A expression in the BL cells. It is possible that SH2D1A is expressed in a narrow window of B cell development represented by germinal center cells.
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PMID:SH2D1A expression in Burkitt lymphoma cells is restricted to EBV positive group I lines and is downregulated in parallel with immunoblastic transformation. 1211 26

Most current classifications of lymphoid neoplasms define the tumors based on the cell of origin, phenotype, genetic abnormalities, and clinical features. Here it is proposed that human lymphocytic tumors can be categorized based on the propensity and capacity of the tumor cells to undergo apoptosis. The first category is defined by malignant cells that are resistant to apoptosis due to expression of anti-apoptotic factors such as bcl-2 and cellular inhibitors of apoptosis (IAPs). These tumors would include CLL and follicular lymphomas, as well as some malignancies in which the tumor cells are infected by viruses that co-opt cell survival pathways, such as human T-cell leukemia/lymphoma virus (HTLV)-1. The second category, in which the malignant cells are apoptosis-prone, would include tumors arising in the context of impaired cytotoxic T-cell function. These neoplasms would include some human immunodeficiency virus (HIV)-related lymphomas such as Burkitt's lymphoma, and post-transplantation lymphomas. The third category would include neoplasms of intermediate sensitivity to apoptosis, some of which are associated with infection such as mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach. Although this classification is tentative, it should evolve in parallel with our understanding of pathogenic mechanisms in lymphoid neoplasia, and provides a novel framework with which to consider the appropriateness of specific therapeutic strategies. Distinctions among lymphocytic tumors in terms of the likelihood of response to therapies such as antisense to bcl-2 related proteins, inhibitors of NF-kappa B activity, and new approaches aimed at bolstering the host's immune response, would cross standard classifications based on the T or B-cell origin of the tumor cells.
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PMID:Apoptosis in lymphocytic leukemias and lymphomas. 1219 30

Mutations or deletions in the SH2D1A (src homology 2 domain protein 1A) gene result in a severe immunodeficiency called X-linked lymphoproliferative (XLP) disease. XLP is primarily characterized by a defective immune response against the Epstein-Barr virus (EBV), resulting in an unusually severe and often fatal clinical course following EBV infection. The second major cause of death is the development of B cell lymphomas, both in EBV-infected and EBV-negative patients. To study whether the clinical manifestation of XLP gene defects and/or polymorphisms extends beyond the classically recognized phenotype, we analyzed patients for the presence of SH2D1A gene alterations who presented with fatal or nonfatal, yet unusually severe or chronic EBV infections, and other possibly EBV-associated diseases, such as Hodgkin's lymphomas or nonendemic Burkitt's lymphomas and Burkitt-type leukemias. We identified mutations of the SH2D1A gene only in the majority of patients presenting with fatal mononucleosis or an XLP family history, but not in any of the other patients studied. The only alteration determined was a polymorphism in the 5' region of the SH2D1A gene both in patient groups as well as in controls.
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PMID:Analysis of SH2D1A mutations in patients with severe Epstein-Barr virus infections, Burkitt's lymphoma, and Hodgkin's lymphoma. 1222 1

Burkitt's lymphoma and small noncleaved Burkitt's-like lymphoma are rare and are highly aggressive forms of non-Hodgkin's lymphoma that are characterized by dysregulation of the c-myc oncogene. Patients with human immunodeficiency virus (HIV) also appear to be at risk for developing Burkitt's lymphomas. Treatment options for Burkitt's lymphoma involve complex chemotherapy regimens that contain as many as 10 cytotoxic agents. Approximately 50%-80% of adult patients with Burkitt's lymphoma or small, noncleaved lymphoma can be cured with these intensive chemotherapy regimens, and in pediatric populations, the cure rate is even higher. However, a number of factors often compromise the outcome of patients with Burkitt's lymphoma. For instance, the high proliferation rate of Burkitt's lymphoma enhances the risk for tumor lysis syndrome, which results from metabolic imbalances, such as hyperuricemia, that occur as large numbers of malignant cells are lysed during cytotoxic chemotherapy. Standard treatment for tumor lysis syndrome includes adjustments in the chemotherapy regimen, vigorous hydration, administration of a uric acid synthesis inhibitor like allopurinol, and alkalinization. The administration of recombinant urate oxidase (rasburicase) also has been shown to provide effective prophylaxis against hyperuricemia in pediatric and adult patients with hematologic malignancies. The lifetime risk of developing central nervous system disease is 20%-30% for Burkitt's lymphoma. Consequently all chemotherapy regimens with activity in Burkitt's lymphoma utilize some form of central nervous system prophylaxis, such as systemic or intrathecal methotrexate or cytarabine. In the past, patients with HIV who developed Burkitt's lymphoma often received inadequate chemotherapy doses because of their immunosuppression. With the discovery of highly active antiretroviral therapy, the ability to treat and control Burkitt's lymphoma in patients with HIV has improved.
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PMID:Challenges in the management of Burkitt's lymphoma. 1252 85

Burkitt's lymphoma (BL) is one of the fastest growing malignancies in the pediatric population in the United States. BL is a high-grade B-cell Non-Hodgkin's lymphoma (NHL) which exists in endemic, sporadic, and human immunodeficiency-associated subtypes. The African, or endemic, variant usually involves the maxilla and other facial bones while head and neck manifestations in non-endemic BL are rare. We present three unusual present ations of sporadic BL stemming from Waldeyer's ring and the orbit. The clinical and pathologic features of BL are reviewed.
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PMID:Sporadic Burkitt's lymphoma of the head and neck in the pediatric population. 1256 Jan 51

The majority of AIDS-related non-Hodgkin's lymphomas are clinically aggressive monoclonal B-cell Burkitt's lymphomas, large cell lymphomas, or immunoblastic lymphomas. In contrast, the lymphoid proliferations arising in solid organ transplant recipients, collectively referred to as posttransplantation lymphoproliferative disorders (PT-LPDs), represent a clinically and histopathologically heterogeneous group of Epstein-Barr virus (EBV)-driven B-cell proliferations of variable clonal composition. During a retrospective histopathologic review of lymphoid proliferations associated with human immunodeficiency virus (HIV) infection we identified 10 cases that morphologically resemble the polymorphic PT-LPDs. They arose in lymph nodes (five), lungs (two), and the parotid gland, perineum, and skin (one each). They exhibit a diffuse growth pattern and are composed of a polymorphic lymphoid cell population exhibiting a variable degree of plasmacytic differentiation, cytologic atypia, and numbers of atypical immunoblasts. A clonal B-cell population was detected by immunoglobulin heavy and light chain gene rearrangement and/or EBV terminal repeat analysis in 8 of the 10 (80%) cases by Southern blotting. The nongermline hybridizing bands were usually faint, however, suggesting that the clonal B-cell population represented only a subpopulation within the polymorphic lesion. Strong clonal rearrangement bands were present in one case in which there was clear morphologic evidence of transformation to diffuse large cell lymphoma. This case exhibited C-MYC, BCL-6, and p53 gene mutations. One other case exhibited a p53 gene mutation. The remaining eight cases lacked C-MYC, BCL-6, RAS, and p53 gene alterations. Clonal EBV infection was detected in 4 of the 10 (40%) lesions. Like EBV-containing PT-LPDs, all four EBV-positive HIV-associated polymorphic lesions were associated with type A EBV. The Kaposi's sarcoma-associated herpesvirus was detectable in two cases by polymerase chain reaction analysis, but not by Southern blotting. In situ hybridization demonstrated Kaposi's sarcoma-associated herpesvirus in some of the cytologically malignant-appearing cells. In conclusion, polymorphic B-cell lymphoproliferative disorders comparable morphologically and molecularly to those arising after solid organ transplantation also occur in association with HIV infection. As in the case of their polymorphic PT-LPD counterparts, their malignant status, biologic significance, and relationship to monomorphic B-cell lymphomas remain to be elucidated.
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PMID:Human immunodeficiency virus (HIV)-associated polymorphic lymphoproliferative disorders. 1260 85

The World Health Organisation classification reports three subcategories of Burkitt's lymphoma (BL)--endemic, non-endemic, and immunodeficiency associated--proposed to reflect the major clinical and genetic subtypes of this disease. These different types of BL have been reviewed and studied by immunohistochemistry and molecular methods. The results point out the heterogeneity of BL and suggest that AIDS related BL may have a different pathogenesis from that of classic BL.
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PMID:Burkitt's lymphoma: new insights into molecular pathogenesis. 1261 94

Epstein-Barr virus (EBV) is associated with lymphoma in immunocompromised patients. This study provides evidence that the expression of EBV nuclear antigen-3 genes can be directed from the F promoter in different type I Burkitt's lymphoma cell lines and in some lymphomas from human immunodeficiency virus-infected patients. This expression occurs predominantly after induction of the EBV lytic cycle.
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PMID:Heterogeneous Epstein-Barr virus latent gene expression in AIDS-associated lymphomas and in type I Burkitt's lymphoma cell lines. 1265 96


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